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Now Takeda offers rebate if lung cancer drug fails to work
The rebate offer is for brigatinib (Alunbrig) which is approved for the treatment of adults with anaplastic lymphoma kinase positive (ALK+) metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.
The move follows a rebate offer from Pfizer for crizotinib (Xalkori), which is also approved for ALK+ (as well as ROS1+) NSCLC, and also for ALK+ anaplastic large cell lymphoma
For its offer, Takeda has teamed up with Point32Health, the second-largest health plan in New England with about 2.3 million members. The new agreement will make brigatinib widely available to patients who may benefit from its use, say the companies.
If a patient is unable to remain on brigatinib for 3 months or longer because of effectiveness or tolerability, Takeda will refund a yet unspecified amount of money to Point32Health. Brigatinib’s list price is $17,000 for a month’s treatment.
“Given the importance of facilitating cutting-edge oncology treatment and also the reality that not all patients show a positive response, reimbursement for oncology treatments is an area that is prime for innovative financing approaches,” said Michael Sherman, MD, chief medical officer and executive vice president, Point32Health, in a statement. “Collaborating with Takeda to share risk makes this agreement a crucial milestone in bringing cost-effectiveness to cancer care.”
The Pfizer program for crizotinib is somewhat different. For one thing, Pfizer’s refund is offered to any patient who qualifies and not just those who are covered by a specific plan. Second, Takeda is thus far only refunding money to the insurer, whereas Pfizer will also reimburse patients for out-of-pocket expenses.
There is a similar approach that has been offered by Novartis for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.
In addition, Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run health care system collected 200 million euros ($220 million) in refunds.
A version of this article first appeared on Medscape.com.
The rebate offer is for brigatinib (Alunbrig) which is approved for the treatment of adults with anaplastic lymphoma kinase positive (ALK+) metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.
The move follows a rebate offer from Pfizer for crizotinib (Xalkori), which is also approved for ALK+ (as well as ROS1+) NSCLC, and also for ALK+ anaplastic large cell lymphoma
For its offer, Takeda has teamed up with Point32Health, the second-largest health plan in New England with about 2.3 million members. The new agreement will make brigatinib widely available to patients who may benefit from its use, say the companies.
If a patient is unable to remain on brigatinib for 3 months or longer because of effectiveness or tolerability, Takeda will refund a yet unspecified amount of money to Point32Health. Brigatinib’s list price is $17,000 for a month’s treatment.
“Given the importance of facilitating cutting-edge oncology treatment and also the reality that not all patients show a positive response, reimbursement for oncology treatments is an area that is prime for innovative financing approaches,” said Michael Sherman, MD, chief medical officer and executive vice president, Point32Health, in a statement. “Collaborating with Takeda to share risk makes this agreement a crucial milestone in bringing cost-effectiveness to cancer care.”
The Pfizer program for crizotinib is somewhat different. For one thing, Pfizer’s refund is offered to any patient who qualifies and not just those who are covered by a specific plan. Second, Takeda is thus far only refunding money to the insurer, whereas Pfizer will also reimburse patients for out-of-pocket expenses.
There is a similar approach that has been offered by Novartis for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.
In addition, Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run health care system collected 200 million euros ($220 million) in refunds.
A version of this article first appeared on Medscape.com.
The rebate offer is for brigatinib (Alunbrig) which is approved for the treatment of adults with anaplastic lymphoma kinase positive (ALK+) metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.
The move follows a rebate offer from Pfizer for crizotinib (Xalkori), which is also approved for ALK+ (as well as ROS1+) NSCLC, and also for ALK+ anaplastic large cell lymphoma
For its offer, Takeda has teamed up with Point32Health, the second-largest health plan in New England with about 2.3 million members. The new agreement will make brigatinib widely available to patients who may benefit from its use, say the companies.
If a patient is unable to remain on brigatinib for 3 months or longer because of effectiveness or tolerability, Takeda will refund a yet unspecified amount of money to Point32Health. Brigatinib’s list price is $17,000 for a month’s treatment.
“Given the importance of facilitating cutting-edge oncology treatment and also the reality that not all patients show a positive response, reimbursement for oncology treatments is an area that is prime for innovative financing approaches,” said Michael Sherman, MD, chief medical officer and executive vice president, Point32Health, in a statement. “Collaborating with Takeda to share risk makes this agreement a crucial milestone in bringing cost-effectiveness to cancer care.”
The Pfizer program for crizotinib is somewhat different. For one thing, Pfizer’s refund is offered to any patient who qualifies and not just those who are covered by a specific plan. Second, Takeda is thus far only refunding money to the insurer, whereas Pfizer will also reimburse patients for out-of-pocket expenses.
There is a similar approach that has been offered by Novartis for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.
In addition, Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run health care system collected 200 million euros ($220 million) in refunds.
A version of this article first appeared on Medscape.com.
Pfizer offers refund if drug ‘doesn’t work’
The high cost of new cancer drugs has been the subject of many debates and discussions, but the issue remains largely unresolved.
Now, one pharmaceutical company is offering a refund if its drug “doesn’t work.”
For what it says is the first time in the industry,
“Through this pilot program, Pfizer will offer a warranty to patients and health plans -- Medicare Part D, commercial and those who pay cash -- who are prescribed Xalkori for an FDA [US Food and Drug Administration]–approved indication,” said a company spokesperson.
Although Pfizer claims that its pilot program is a first in the industry, there have been others that are similar.
In 2017, Novartis offered something similar for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.
Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run healthcare system collected €200 million ($220 million) in refunds.
Pfizer pledge
Crizotinib is a selective tyrosine kinase inhibitor used mainly in the treatment of metastatic non–small cell lung cancer for patients whose tumors are positive for ALK or ROS1, as detected by an FDA-approved test. This indication was approved a decade ago. Another indication, ALK-positive anaplastic large cell lymphoma, was added earlier this year.
Details of the Pfizer Pledge are posted on Pfizer’s website. Eligible patients are those for whom crizotinib is discontinued before the fourth 30-day supply is dispensed by the patient’s pharmacy.
“The warranty will reimburse an amount equal to the cost paid for the medicine,” the spokesperson added. “The insurance-backed warranty pilot program will be insured and managed by AIG.”
This program is only available for patients who reside in the United States.
If use of crizotinib is discontinued and documentation of ineffectiveness is provided, Pfizer will refund the out-of-pocket amount that was paid for up to the first three bottles (30-day supply) of crizotinib, up to a maximum of $19,144 for each month’s supply, or a total of $57,432. Pfizer will also refund the cost that was paid by Medicare or a commercial insurer.
“Also, we have made sure to develop a program that also allows for Medicare patients to be eligible, since they are exempt from copay cards and at risk for significant financial burden when starting an oncology treatment,” said the spokesperson.
The pilot program is available to patients who began taking crizotinib from June 1, 2021, through December 31, 2021.
So far, Pfizer is offering this warranty only for crizotinib, but that may change in the future.
“Once the pilot is complete, we will assess learnings and consider whether to build a more robust, scalable program capable of supporting multiple products,” the Pfizer spokesperson commented.
Previous scheme ended in court
Pfizer had previously tried a different approach to reducing drug costs: it had attempted to offer copay support programs to Medicare patients who were prescribed its cardiac drug tafamidis (Vyndaqe, Vyndamax).
Tafamidis, launched in 2019, is used for patients with transthyretin amyloid cardiomyopathy. For those patients, it has been shown to reduce all-cause mortality and cardiovascular hospitalizations. It costs about $225,000 a year and has been described as the most expensive cardiovascular drug in the United States.
Earlier this month, a court dismissed Pfizer’s challenge to an anti-kickback law that prevented the company from offering copay support programs to Medicare patients.
The judge ruled that Pfizer’s plan to offer direct payments to patients violated a federal ban on “knowingly or willfully” providing financial support to induce drug purchases, even in the absence of corrupt intent.
Pharmaceutical manufacturers are forbidden from subsidizing copayments for Medicare beneficiaries but are allowed to donate to independent nonprofit organizations that offer copay assistance. Pfizer sued the U.S. Department of Health and Human Services in June 2020 to get a court ruling that their proposed programs were legal.
The new pledge program for crizotinib operates from a different premise, the Pfizer spokesperson commented.
A version of this article first appeared on Medscape.com.
The high cost of new cancer drugs has been the subject of many debates and discussions, but the issue remains largely unresolved.
Now, one pharmaceutical company is offering a refund if its drug “doesn’t work.”
For what it says is the first time in the industry,
“Through this pilot program, Pfizer will offer a warranty to patients and health plans -- Medicare Part D, commercial and those who pay cash -- who are prescribed Xalkori for an FDA [US Food and Drug Administration]–approved indication,” said a company spokesperson.
Although Pfizer claims that its pilot program is a first in the industry, there have been others that are similar.
In 2017, Novartis offered something similar for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.
Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run healthcare system collected €200 million ($220 million) in refunds.
Pfizer pledge
Crizotinib is a selective tyrosine kinase inhibitor used mainly in the treatment of metastatic non–small cell lung cancer for patients whose tumors are positive for ALK or ROS1, as detected by an FDA-approved test. This indication was approved a decade ago. Another indication, ALK-positive anaplastic large cell lymphoma, was added earlier this year.
Details of the Pfizer Pledge are posted on Pfizer’s website. Eligible patients are those for whom crizotinib is discontinued before the fourth 30-day supply is dispensed by the patient’s pharmacy.
“The warranty will reimburse an amount equal to the cost paid for the medicine,” the spokesperson added. “The insurance-backed warranty pilot program will be insured and managed by AIG.”
This program is only available for patients who reside in the United States.
If use of crizotinib is discontinued and documentation of ineffectiveness is provided, Pfizer will refund the out-of-pocket amount that was paid for up to the first three bottles (30-day supply) of crizotinib, up to a maximum of $19,144 for each month’s supply, or a total of $57,432. Pfizer will also refund the cost that was paid by Medicare or a commercial insurer.
“Also, we have made sure to develop a program that also allows for Medicare patients to be eligible, since they are exempt from copay cards and at risk for significant financial burden when starting an oncology treatment,” said the spokesperson.
The pilot program is available to patients who began taking crizotinib from June 1, 2021, through December 31, 2021.
So far, Pfizer is offering this warranty only for crizotinib, but that may change in the future.
“Once the pilot is complete, we will assess learnings and consider whether to build a more robust, scalable program capable of supporting multiple products,” the Pfizer spokesperson commented.
Previous scheme ended in court
Pfizer had previously tried a different approach to reducing drug costs: it had attempted to offer copay support programs to Medicare patients who were prescribed its cardiac drug tafamidis (Vyndaqe, Vyndamax).
Tafamidis, launched in 2019, is used for patients with transthyretin amyloid cardiomyopathy. For those patients, it has been shown to reduce all-cause mortality and cardiovascular hospitalizations. It costs about $225,000 a year and has been described as the most expensive cardiovascular drug in the United States.
Earlier this month, a court dismissed Pfizer’s challenge to an anti-kickback law that prevented the company from offering copay support programs to Medicare patients.
The judge ruled that Pfizer’s plan to offer direct payments to patients violated a federal ban on “knowingly or willfully” providing financial support to induce drug purchases, even in the absence of corrupt intent.
Pharmaceutical manufacturers are forbidden from subsidizing copayments for Medicare beneficiaries but are allowed to donate to independent nonprofit organizations that offer copay assistance. Pfizer sued the U.S. Department of Health and Human Services in June 2020 to get a court ruling that their proposed programs were legal.
The new pledge program for crizotinib operates from a different premise, the Pfizer spokesperson commented.
A version of this article first appeared on Medscape.com.
The high cost of new cancer drugs has been the subject of many debates and discussions, but the issue remains largely unresolved.
Now, one pharmaceutical company is offering a refund if its drug “doesn’t work.”
For what it says is the first time in the industry,
“Through this pilot program, Pfizer will offer a warranty to patients and health plans -- Medicare Part D, commercial and those who pay cash -- who are prescribed Xalkori for an FDA [US Food and Drug Administration]–approved indication,” said a company spokesperson.
Although Pfizer claims that its pilot program is a first in the industry, there have been others that are similar.
In 2017, Novartis offered something similar for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.
Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run healthcare system collected €200 million ($220 million) in refunds.
Pfizer pledge
Crizotinib is a selective tyrosine kinase inhibitor used mainly in the treatment of metastatic non–small cell lung cancer for patients whose tumors are positive for ALK or ROS1, as detected by an FDA-approved test. This indication was approved a decade ago. Another indication, ALK-positive anaplastic large cell lymphoma, was added earlier this year.
Details of the Pfizer Pledge are posted on Pfizer’s website. Eligible patients are those for whom crizotinib is discontinued before the fourth 30-day supply is dispensed by the patient’s pharmacy.
“The warranty will reimburse an amount equal to the cost paid for the medicine,” the spokesperson added. “The insurance-backed warranty pilot program will be insured and managed by AIG.”
This program is only available for patients who reside in the United States.
If use of crizotinib is discontinued and documentation of ineffectiveness is provided, Pfizer will refund the out-of-pocket amount that was paid for up to the first three bottles (30-day supply) of crizotinib, up to a maximum of $19,144 for each month’s supply, or a total of $57,432. Pfizer will also refund the cost that was paid by Medicare or a commercial insurer.
“Also, we have made sure to develop a program that also allows for Medicare patients to be eligible, since they are exempt from copay cards and at risk for significant financial burden when starting an oncology treatment,” said the spokesperson.
The pilot program is available to patients who began taking crizotinib from June 1, 2021, through December 31, 2021.
So far, Pfizer is offering this warranty only for crizotinib, but that may change in the future.
“Once the pilot is complete, we will assess learnings and consider whether to build a more robust, scalable program capable of supporting multiple products,” the Pfizer spokesperson commented.
Previous scheme ended in court
Pfizer had previously tried a different approach to reducing drug costs: it had attempted to offer copay support programs to Medicare patients who were prescribed its cardiac drug tafamidis (Vyndaqe, Vyndamax).
Tafamidis, launched in 2019, is used for patients with transthyretin amyloid cardiomyopathy. For those patients, it has been shown to reduce all-cause mortality and cardiovascular hospitalizations. It costs about $225,000 a year and has been described as the most expensive cardiovascular drug in the United States.
Earlier this month, a court dismissed Pfizer’s challenge to an anti-kickback law that prevented the company from offering copay support programs to Medicare patients.
The judge ruled that Pfizer’s plan to offer direct payments to patients violated a federal ban on “knowingly or willfully” providing financial support to induce drug purchases, even in the absence of corrupt intent.
Pharmaceutical manufacturers are forbidden from subsidizing copayments for Medicare beneficiaries but are allowed to donate to independent nonprofit organizations that offer copay assistance. Pfizer sued the U.S. Department of Health and Human Services in June 2020 to get a court ruling that their proposed programs were legal.
The new pledge program for crizotinib operates from a different premise, the Pfizer spokesperson commented.
A version of this article first appeared on Medscape.com.
Tramadol linked to higher risk of mortality, compared with codeine
Tramadol is increasingly used to manage chronic noncancer pain, but as compared with opioids, it appears to be linked to a higher risk for adverse outcomes, according to new data.
Among a cohort of patients who received a prescription for either tramadol or codeine for orthopedic-related pain, tramadol was significantly associated with a higher risk of mortality, cardiovascular events, and fractures.
However, there was no significant difference in the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders between the two drugs.
“However, this is a retrospective cohort study, and despite it providing information that would otherwise be impossible to gather – such as from randomized controlled trials – clinicians should not solely base their decision on this study,” cautioned lead author Carlen Reyes, MD, PhD, of the Institut Universitari d’Investigació en Atenció Primària (IDIAP Jordi Gol), Barcelona.
Dr. Reyes noted that the intake of tramadol and codeine was analyzed using the number of “packages” that were dispensed, as an approximation of the real intake. “Logically we could think that the more packages dispensed of one drug, the more dose the patient is taking, but this is not always true given the availability of different doses commercialized of tramadol and different doses prescribed,” she said. “Given that we did not account for the real dose prescribed, we can only suspect an increased risk of these outcomes and reinforce the need for further prospective studies with more specific dose-response analysis comparing tramadol and codeine.”
The paper was published Oct. 19 in JAMA.
Tramadol has been considered to be a relatively safe opioid and was even strongly recommended by the American Academy of Orthopaedic Surgeons for patients experiencing symptomatic knee osteoarthritis. The authors point out that studies looking at opioid use from 2019 to 2020 show that tramadol was the most prescribed opioid in England, the Netherlands, and Spain.
In the United States, the age-adjusted rate of drug overdose deaths from synthetic opioids rose from 1.0 per 100 000 in 2013 to 11.4 in 2019. Most of these deaths were attributable to fentanyl but some were also related to tramadol.
But despite its wide use in managing chronic noncancer pain, results of recent studies suggest adverse outcomes as compared with other agents. Last year, one study found that older patients who received tramadol had a significant increase in the risk of hip fracture vs. those using NSAIDs or codeine. Another study, also published in 2020, showed that patients with osteoarthritis who were treated with tramadol had a 20%-50% higher risk of dying during the first year of treatment than did patients who were treated with NSAIDs.
In the current paper, Dr. Reyes and colleagues evaluated the association of tramadol with mortality and other adverse clinical outcomes in outpatient settings, compared with codeine.
They conducted a retrospective, population-based, propensity score–matched cohort study using a primary care database that routinely collects medical records and pharmacy dispensations for more than 80% of the population of Catalonia, Spain. The cohort included people 18 years or older who had been prescribed tramadol or codeine from 2007 to 2017 and were followed up to Dec. 31, 2017.
After propensity score matching, the final analysis included 368,960 participants: 184,480 in the tramadol arm and 184,480 in the codeine arm.
The mean age of patients was 52.7 years in the tramadol arm and 53.5 years in the codeine arm, and the prevalence of cancer was 3.2% and 3.3%, respectively. The most common diagnoses in this cohort were back pain (47.5% vs. 48.5%), neck/shoulder pain (28.6% vs. 29.5%), and osteoarthritis (15.3% vs. 15.5%). The most commonly used drugs were ibuprofen (34.4% vs. 34.3%) and paracetamol/acetaminophen (37.1% vs. 36.8%)
Higher risk of adverse outcomes
As compared with codeine, tramadol use was significantly associated with a higher risk of mortality (13.00 vs. 5.61 per 1,000 person-years; hazard ratio, 2.31; 95% confidence interval, 2.08-2.56); absolute rate differences (7.37 per 1,000 person-years; 95% CI, 6.09-8.78), cardiovascular events (10.03 vs. 8.67 per 1,000 person-years; HR, 1.15; 95% CI, 1.05-1.27; ARD, 1.36 per 1,000 person-years; 95% CI, 0.45-2.36), and fractures (12.26 vs. 8.13 per 1,000 person-years; HR, 1.50; 95% CI, 1.37-1.65; ARD, 4.10 per 1,000 person-years; 95% CI, 3.02-5.29).
A subgroup and sensitivity analysis showed that the increased mortality risk associated with tramadol was significantly higher in younger persons vs. older ones (HR, 3.14; 95% CI, 1.82-5.41 vs. 2.39; 95% CI, 2.20-2.60]; P < .001 for interaction). In addition, women had a significantly greater risk of cardiovascular events versus men (HR, 1.32; 95% CI, 1.19-1.46] vs. 1.03; 95% CI, 0.9-1.13]; P < .001 for interaction).
Potential for confounding
Weighing in on the data, Daniel Solomon, MD, MPH, chief of clinical sciences, division of rheumatology, Brigham and Women’s Hospital, and professor of medicine, Harvard Medical School, Boston, noted that because it is extremely unlikely that anyone will ever conduct a large, head-to-head safety trial comparing different opioids, the results of this paper are important to consider.
“However, as the authors appropriately caution, this type of analysis is limited by the strong potential for residual confounding,” he said. “In other words, even though the authors used state-of-the-art methods to limit imbalances between the patients initiating tramadol versus codeine, there is strong reason to believe that imbalances that may account for the differences in adverse events exist.”
For example, he noted that if one looks at the distribution of comorbid conditions in the before-matching group, tramadol initiators demonstrate a higher frequency of chronic kidney disease, diabetes, and overall chronic comorbid diseases. “This suggests to me that prescribers apply selection criteria when choosing who to prescribe which opioid,” Dr. Solomon explained.
“While the authors’ use of propensity score matching limits confounding, it only can improve balance for measured confounders,” he said. “Other factors not measured in this type of data set – blood pressure, pain, physical activity, tobacco use, body mass index – may still demonstrate imbalances even after matching.”
But after these limitations are taken into consideration, the results remain concerning, Dr. Solomon emphasized, particularly the all-cause mortality excess of tramadol versus codeine users. “This study did not include cause of death, which would help the reader understand why users of tramadol were dying more frequently,” he added. “It also might help in understanding whether this is a true biologic effect or residual confounding.”
Perceived safety
In an accompanying editorial, Howard S. Kim, MD, MS, and colleagues from Northwestern University, Chicago, write that the greatest risk of tramadol may involve the perception that it is “inherently safer than other opioids.”
“In actuality, the mechanisms of action and variable metabolism of tramadol in a given population create considerable therapeutic uncertainty and introduce additional risk exposure,” they say, as demonstrated in the current study.
Therefore, when clinicians determine that an opioid is needed for pain relief, it may be a better option to select a pure opioid agonist that has a more predictable therapeutic effect and known adverse effect profile, such as morphine or hydrocodone. “This would allow clinicians and patients to more properly weigh the risks and benefits of initiating opioid therapy through shared decision-making and prompt the level of counseling on safe use, storage, and disposal practices that all opioids deserve,” write the editorialists.
The study was funded by the Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina. The research was supported by the National Institute for Health Research Oxford Biomedical Research Centre. Dr. Reyes has disclosed no relevant financial relationships. Dr. Solomon disclosed salary support from research contracts to his hospital from Amgen, AbbVie, Moderna, the Rheumatology Research Foundation, and National Institutes of Health; and royalties from UpToDate. Dr. Kim reported unrelated grant support from the Agency for Healthcare Research and Quality.
A version of this article first appeared on Medscape.com.
Tramadol is increasingly used to manage chronic noncancer pain, but as compared with opioids, it appears to be linked to a higher risk for adverse outcomes, according to new data.
Among a cohort of patients who received a prescription for either tramadol or codeine for orthopedic-related pain, tramadol was significantly associated with a higher risk of mortality, cardiovascular events, and fractures.
However, there was no significant difference in the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders between the two drugs.
“However, this is a retrospective cohort study, and despite it providing information that would otherwise be impossible to gather – such as from randomized controlled trials – clinicians should not solely base their decision on this study,” cautioned lead author Carlen Reyes, MD, PhD, of the Institut Universitari d’Investigació en Atenció Primària (IDIAP Jordi Gol), Barcelona.
Dr. Reyes noted that the intake of tramadol and codeine was analyzed using the number of “packages” that were dispensed, as an approximation of the real intake. “Logically we could think that the more packages dispensed of one drug, the more dose the patient is taking, but this is not always true given the availability of different doses commercialized of tramadol and different doses prescribed,” she said. “Given that we did not account for the real dose prescribed, we can only suspect an increased risk of these outcomes and reinforce the need for further prospective studies with more specific dose-response analysis comparing tramadol and codeine.”
The paper was published Oct. 19 in JAMA.
Tramadol has been considered to be a relatively safe opioid and was even strongly recommended by the American Academy of Orthopaedic Surgeons for patients experiencing symptomatic knee osteoarthritis. The authors point out that studies looking at opioid use from 2019 to 2020 show that tramadol was the most prescribed opioid in England, the Netherlands, and Spain.
In the United States, the age-adjusted rate of drug overdose deaths from synthetic opioids rose from 1.0 per 100 000 in 2013 to 11.4 in 2019. Most of these deaths were attributable to fentanyl but some were also related to tramadol.
But despite its wide use in managing chronic noncancer pain, results of recent studies suggest adverse outcomes as compared with other agents. Last year, one study found that older patients who received tramadol had a significant increase in the risk of hip fracture vs. those using NSAIDs or codeine. Another study, also published in 2020, showed that patients with osteoarthritis who were treated with tramadol had a 20%-50% higher risk of dying during the first year of treatment than did patients who were treated with NSAIDs.
In the current paper, Dr. Reyes and colleagues evaluated the association of tramadol with mortality and other adverse clinical outcomes in outpatient settings, compared with codeine.
They conducted a retrospective, population-based, propensity score–matched cohort study using a primary care database that routinely collects medical records and pharmacy dispensations for more than 80% of the population of Catalonia, Spain. The cohort included people 18 years or older who had been prescribed tramadol or codeine from 2007 to 2017 and were followed up to Dec. 31, 2017.
After propensity score matching, the final analysis included 368,960 participants: 184,480 in the tramadol arm and 184,480 in the codeine arm.
The mean age of patients was 52.7 years in the tramadol arm and 53.5 years in the codeine arm, and the prevalence of cancer was 3.2% and 3.3%, respectively. The most common diagnoses in this cohort were back pain (47.5% vs. 48.5%), neck/shoulder pain (28.6% vs. 29.5%), and osteoarthritis (15.3% vs. 15.5%). The most commonly used drugs were ibuprofen (34.4% vs. 34.3%) and paracetamol/acetaminophen (37.1% vs. 36.8%)
Higher risk of adverse outcomes
As compared with codeine, tramadol use was significantly associated with a higher risk of mortality (13.00 vs. 5.61 per 1,000 person-years; hazard ratio, 2.31; 95% confidence interval, 2.08-2.56); absolute rate differences (7.37 per 1,000 person-years; 95% CI, 6.09-8.78), cardiovascular events (10.03 vs. 8.67 per 1,000 person-years; HR, 1.15; 95% CI, 1.05-1.27; ARD, 1.36 per 1,000 person-years; 95% CI, 0.45-2.36), and fractures (12.26 vs. 8.13 per 1,000 person-years; HR, 1.50; 95% CI, 1.37-1.65; ARD, 4.10 per 1,000 person-years; 95% CI, 3.02-5.29).
A subgroup and sensitivity analysis showed that the increased mortality risk associated with tramadol was significantly higher in younger persons vs. older ones (HR, 3.14; 95% CI, 1.82-5.41 vs. 2.39; 95% CI, 2.20-2.60]; P < .001 for interaction). In addition, women had a significantly greater risk of cardiovascular events versus men (HR, 1.32; 95% CI, 1.19-1.46] vs. 1.03; 95% CI, 0.9-1.13]; P < .001 for interaction).
Potential for confounding
Weighing in on the data, Daniel Solomon, MD, MPH, chief of clinical sciences, division of rheumatology, Brigham and Women’s Hospital, and professor of medicine, Harvard Medical School, Boston, noted that because it is extremely unlikely that anyone will ever conduct a large, head-to-head safety trial comparing different opioids, the results of this paper are important to consider.
“However, as the authors appropriately caution, this type of analysis is limited by the strong potential for residual confounding,” he said. “In other words, even though the authors used state-of-the-art methods to limit imbalances between the patients initiating tramadol versus codeine, there is strong reason to believe that imbalances that may account for the differences in adverse events exist.”
For example, he noted that if one looks at the distribution of comorbid conditions in the before-matching group, tramadol initiators demonstrate a higher frequency of chronic kidney disease, diabetes, and overall chronic comorbid diseases. “This suggests to me that prescribers apply selection criteria when choosing who to prescribe which opioid,” Dr. Solomon explained.
“While the authors’ use of propensity score matching limits confounding, it only can improve balance for measured confounders,” he said. “Other factors not measured in this type of data set – blood pressure, pain, physical activity, tobacco use, body mass index – may still demonstrate imbalances even after matching.”
But after these limitations are taken into consideration, the results remain concerning, Dr. Solomon emphasized, particularly the all-cause mortality excess of tramadol versus codeine users. “This study did not include cause of death, which would help the reader understand why users of tramadol were dying more frequently,” he added. “It also might help in understanding whether this is a true biologic effect or residual confounding.”
Perceived safety
In an accompanying editorial, Howard S. Kim, MD, MS, and colleagues from Northwestern University, Chicago, write that the greatest risk of tramadol may involve the perception that it is “inherently safer than other opioids.”
“In actuality, the mechanisms of action and variable metabolism of tramadol in a given population create considerable therapeutic uncertainty and introduce additional risk exposure,” they say, as demonstrated in the current study.
Therefore, when clinicians determine that an opioid is needed for pain relief, it may be a better option to select a pure opioid agonist that has a more predictable therapeutic effect and known adverse effect profile, such as morphine or hydrocodone. “This would allow clinicians and patients to more properly weigh the risks and benefits of initiating opioid therapy through shared decision-making and prompt the level of counseling on safe use, storage, and disposal practices that all opioids deserve,” write the editorialists.
The study was funded by the Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina. The research was supported by the National Institute for Health Research Oxford Biomedical Research Centre. Dr. Reyes has disclosed no relevant financial relationships. Dr. Solomon disclosed salary support from research contracts to his hospital from Amgen, AbbVie, Moderna, the Rheumatology Research Foundation, and National Institutes of Health; and royalties from UpToDate. Dr. Kim reported unrelated grant support from the Agency for Healthcare Research and Quality.
A version of this article first appeared on Medscape.com.
Tramadol is increasingly used to manage chronic noncancer pain, but as compared with opioids, it appears to be linked to a higher risk for adverse outcomes, according to new data.
Among a cohort of patients who received a prescription for either tramadol or codeine for orthopedic-related pain, tramadol was significantly associated with a higher risk of mortality, cardiovascular events, and fractures.
However, there was no significant difference in the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders between the two drugs.
“However, this is a retrospective cohort study, and despite it providing information that would otherwise be impossible to gather – such as from randomized controlled trials – clinicians should not solely base their decision on this study,” cautioned lead author Carlen Reyes, MD, PhD, of the Institut Universitari d’Investigació en Atenció Primària (IDIAP Jordi Gol), Barcelona.
Dr. Reyes noted that the intake of tramadol and codeine was analyzed using the number of “packages” that were dispensed, as an approximation of the real intake. “Logically we could think that the more packages dispensed of one drug, the more dose the patient is taking, but this is not always true given the availability of different doses commercialized of tramadol and different doses prescribed,” she said. “Given that we did not account for the real dose prescribed, we can only suspect an increased risk of these outcomes and reinforce the need for further prospective studies with more specific dose-response analysis comparing tramadol and codeine.”
The paper was published Oct. 19 in JAMA.
Tramadol has been considered to be a relatively safe opioid and was even strongly recommended by the American Academy of Orthopaedic Surgeons for patients experiencing symptomatic knee osteoarthritis. The authors point out that studies looking at opioid use from 2019 to 2020 show that tramadol was the most prescribed opioid in England, the Netherlands, and Spain.
In the United States, the age-adjusted rate of drug overdose deaths from synthetic opioids rose from 1.0 per 100 000 in 2013 to 11.4 in 2019. Most of these deaths were attributable to fentanyl but some were also related to tramadol.
But despite its wide use in managing chronic noncancer pain, results of recent studies suggest adverse outcomes as compared with other agents. Last year, one study found that older patients who received tramadol had a significant increase in the risk of hip fracture vs. those using NSAIDs or codeine. Another study, also published in 2020, showed that patients with osteoarthritis who were treated with tramadol had a 20%-50% higher risk of dying during the first year of treatment than did patients who were treated with NSAIDs.
In the current paper, Dr. Reyes and colleagues evaluated the association of tramadol with mortality and other adverse clinical outcomes in outpatient settings, compared with codeine.
They conducted a retrospective, population-based, propensity score–matched cohort study using a primary care database that routinely collects medical records and pharmacy dispensations for more than 80% of the population of Catalonia, Spain. The cohort included people 18 years or older who had been prescribed tramadol or codeine from 2007 to 2017 and were followed up to Dec. 31, 2017.
After propensity score matching, the final analysis included 368,960 participants: 184,480 in the tramadol arm and 184,480 in the codeine arm.
The mean age of patients was 52.7 years in the tramadol arm and 53.5 years in the codeine arm, and the prevalence of cancer was 3.2% and 3.3%, respectively. The most common diagnoses in this cohort were back pain (47.5% vs. 48.5%), neck/shoulder pain (28.6% vs. 29.5%), and osteoarthritis (15.3% vs. 15.5%). The most commonly used drugs were ibuprofen (34.4% vs. 34.3%) and paracetamol/acetaminophen (37.1% vs. 36.8%)
Higher risk of adverse outcomes
As compared with codeine, tramadol use was significantly associated with a higher risk of mortality (13.00 vs. 5.61 per 1,000 person-years; hazard ratio, 2.31; 95% confidence interval, 2.08-2.56); absolute rate differences (7.37 per 1,000 person-years; 95% CI, 6.09-8.78), cardiovascular events (10.03 vs. 8.67 per 1,000 person-years; HR, 1.15; 95% CI, 1.05-1.27; ARD, 1.36 per 1,000 person-years; 95% CI, 0.45-2.36), and fractures (12.26 vs. 8.13 per 1,000 person-years; HR, 1.50; 95% CI, 1.37-1.65; ARD, 4.10 per 1,000 person-years; 95% CI, 3.02-5.29).
A subgroup and sensitivity analysis showed that the increased mortality risk associated with tramadol was significantly higher in younger persons vs. older ones (HR, 3.14; 95% CI, 1.82-5.41 vs. 2.39; 95% CI, 2.20-2.60]; P < .001 for interaction). In addition, women had a significantly greater risk of cardiovascular events versus men (HR, 1.32; 95% CI, 1.19-1.46] vs. 1.03; 95% CI, 0.9-1.13]; P < .001 for interaction).
Potential for confounding
Weighing in on the data, Daniel Solomon, MD, MPH, chief of clinical sciences, division of rheumatology, Brigham and Women’s Hospital, and professor of medicine, Harvard Medical School, Boston, noted that because it is extremely unlikely that anyone will ever conduct a large, head-to-head safety trial comparing different opioids, the results of this paper are important to consider.
“However, as the authors appropriately caution, this type of analysis is limited by the strong potential for residual confounding,” he said. “In other words, even though the authors used state-of-the-art methods to limit imbalances between the patients initiating tramadol versus codeine, there is strong reason to believe that imbalances that may account for the differences in adverse events exist.”
For example, he noted that if one looks at the distribution of comorbid conditions in the before-matching group, tramadol initiators demonstrate a higher frequency of chronic kidney disease, diabetes, and overall chronic comorbid diseases. “This suggests to me that prescribers apply selection criteria when choosing who to prescribe which opioid,” Dr. Solomon explained.
“While the authors’ use of propensity score matching limits confounding, it only can improve balance for measured confounders,” he said. “Other factors not measured in this type of data set – blood pressure, pain, physical activity, tobacco use, body mass index – may still demonstrate imbalances even after matching.”
But after these limitations are taken into consideration, the results remain concerning, Dr. Solomon emphasized, particularly the all-cause mortality excess of tramadol versus codeine users. “This study did not include cause of death, which would help the reader understand why users of tramadol were dying more frequently,” he added. “It also might help in understanding whether this is a true biologic effect or residual confounding.”
Perceived safety
In an accompanying editorial, Howard S. Kim, MD, MS, and colleagues from Northwestern University, Chicago, write that the greatest risk of tramadol may involve the perception that it is “inherently safer than other opioids.”
“In actuality, the mechanisms of action and variable metabolism of tramadol in a given population create considerable therapeutic uncertainty and introduce additional risk exposure,” they say, as demonstrated in the current study.
Therefore, when clinicians determine that an opioid is needed for pain relief, it may be a better option to select a pure opioid agonist that has a more predictable therapeutic effect and known adverse effect profile, such as morphine or hydrocodone. “This would allow clinicians and patients to more properly weigh the risks and benefits of initiating opioid therapy through shared decision-making and prompt the level of counseling on safe use, storage, and disposal practices that all opioids deserve,” write the editorialists.
The study was funded by the Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina. The research was supported by the National Institute for Health Research Oxford Biomedical Research Centre. Dr. Reyes has disclosed no relevant financial relationships. Dr. Solomon disclosed salary support from research contracts to his hospital from Amgen, AbbVie, Moderna, the Rheumatology Research Foundation, and National Institutes of Health; and royalties from UpToDate. Dr. Kim reported unrelated grant support from the Agency for Healthcare Research and Quality.
A version of this article first appeared on Medscape.com.
No advantages to using ADM in implant-based breast reconstruction
A European study involving 155 women found that the use of acellular dermal matrix (ADM) did not lead to fewer reoperations, nor was it superior in terms of health-related quality of life or patient-reported cosmetic outcomes.
“We feel that women considering implant-based reconstructions for breast cancer should be informed about the lack of evidence supporting its advantage,” said lead author Fredrik Lohmander MD, department of breast and endocrine surgery, section of breast urgery, Karolinska University Hospital, Stockholm.
It is difficult to say generally whether ADM should be used in IBBR, he noted. “We can only conclude from our trial that there is no hard evidence that ADM is beneficial when performing breast reconstructions with implants,” he said in an interview. “In selected patients, ADM might be indicated.”
The study was conducted in Sweden and the United Kingdom. “Mostly because of high costs, ADM in implant-based breast reconstructions in Sweden is not frequently used,” Dr. Lohmander said. “It is slightly more common in the U.K., but much more common in the U.S.A.”
Although biological meshes have received regulatory approval by the U.S. Food and Drug Administration for reconstructive purposes, ADM has not been approved for use in breast reconstruction surgery, and its use in this setting is off label.
The study was published online October 1 in JAMA Network Open.
Any advantage to using mesh device?
Previous studies of ADMs suggested that the mesh device conferred several benefits, including superior cosmetic results, less need for tissue expanders, fewer elective reoperations, and less capsular contracture. The use of a mesh device also enlarges the subpectoral pocket, which allows for larger fixed-volume implants, the authors note.
However, these suggested advantages have not been universally accepted, and the authors note that there have been reports of associated harm, such as higher rates of infection and implant loss.
The new study included 135 women from five centers in Sweden and the United Kingdom. The patients had breast cancer and had planned to undergo mastectomy and immediate IBBR between 2014 and May 2017.
The primary endpoint was the number of repeat surgeries at 2 years.
At the 2-year follow-up, 31 patients (48%) in the ADM group had undergone at least one reoperation on the ipsilateral side, vs 35 (54%) in the control group (P = .54). Results were similar for the contralateral side: 34 (53%) vs 31 (48%).
Two patients in the ADM group and three patients in the control group underwent a risk-reducing mastectomy on the contralateral side. These five surgeries were included in the final analysis.
For nine patients (14%) in the ADM arm, the implant was removed. Four of the removals took place within 6 months after early surgical complications. In the control group, seven patients (11%) underwent implant removal; four were removed within 6 months, owing to early surgical complications.
The secondary endpoint was postoperative health-related quality of life, including perception of body image and satisfaction with cosmetic outcome. There were no significant differences between the two groups.
Some questions remain
Approached for comment on the study, Sameer A. Patel, MD, FACS, chief of plastic and reconstructive surgery at Fox Chase Cancer Center, Philadelphia, noted that the practice of using AMD for breast reconstruction is quite common in the United States, so these data are informative and add to the current understanding of the value of ADM in breast reconstruction. “The study hypothesized that the use of ADM would reduce the number of reoperations within the first 24 months, which it did not,” he said. “This is despite the fact that the ADM group had a significantly higher number of direct-to-implant reconstructions.”
Importantly, the study showed that patient-reported outcomes, as opposed to surgeon’s evaluation of outcomes, were also not different for the most part between the two groups, Dr. Patel pointed out. “The only exception of small favorable advantage in the ADM group was for fitting bras,” he said.
However, there were limitations to the study’s endpoint. “I would add that there are some purported advantages of using ADM, such as reduction in postoperative pain and reduction in length of hospital stay, which are not evaluated by this study,” Patel explained. “Also, I am not certain that they can conclude from this study that capsular contracture is not reduced, because it is not designed to evaluate that.”
But the biggest limitation is one that study authors point out in their discussion at the end of the article, he added. “The use of prepectoral reconstruction is rapidly replacing the dual plane reconstruction that this paper used in the ADM group,” Dr. Patel said. “The role of ADM in prepectoral reconstruction is somewhat different than in the dual plane reconstruction, and so these results may not necessarily be extrapolated to prepectoral reconstruction.”
The study was funded with grants from the Swedish Breast Cancer Association and Stockholm City Council. The trial was initiated by Karolinska University Hospital and Karolinska Institutet. Acelity (an Allergan company) supplied the study with acellular dermal matrix meshes. Dr. Lohmander and Dr. Patel have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A European study involving 155 women found that the use of acellular dermal matrix (ADM) did not lead to fewer reoperations, nor was it superior in terms of health-related quality of life or patient-reported cosmetic outcomes.
“We feel that women considering implant-based reconstructions for breast cancer should be informed about the lack of evidence supporting its advantage,” said lead author Fredrik Lohmander MD, department of breast and endocrine surgery, section of breast urgery, Karolinska University Hospital, Stockholm.
It is difficult to say generally whether ADM should be used in IBBR, he noted. “We can only conclude from our trial that there is no hard evidence that ADM is beneficial when performing breast reconstructions with implants,” he said in an interview. “In selected patients, ADM might be indicated.”
The study was conducted in Sweden and the United Kingdom. “Mostly because of high costs, ADM in implant-based breast reconstructions in Sweden is not frequently used,” Dr. Lohmander said. “It is slightly more common in the U.K., but much more common in the U.S.A.”
Although biological meshes have received regulatory approval by the U.S. Food and Drug Administration for reconstructive purposes, ADM has not been approved for use in breast reconstruction surgery, and its use in this setting is off label.
The study was published online October 1 in JAMA Network Open.
Any advantage to using mesh device?
Previous studies of ADMs suggested that the mesh device conferred several benefits, including superior cosmetic results, less need for tissue expanders, fewer elective reoperations, and less capsular contracture. The use of a mesh device also enlarges the subpectoral pocket, which allows for larger fixed-volume implants, the authors note.
However, these suggested advantages have not been universally accepted, and the authors note that there have been reports of associated harm, such as higher rates of infection and implant loss.
The new study included 135 women from five centers in Sweden and the United Kingdom. The patients had breast cancer and had planned to undergo mastectomy and immediate IBBR between 2014 and May 2017.
The primary endpoint was the number of repeat surgeries at 2 years.
At the 2-year follow-up, 31 patients (48%) in the ADM group had undergone at least one reoperation on the ipsilateral side, vs 35 (54%) in the control group (P = .54). Results were similar for the contralateral side: 34 (53%) vs 31 (48%).
Two patients in the ADM group and three patients in the control group underwent a risk-reducing mastectomy on the contralateral side. These five surgeries were included in the final analysis.
For nine patients (14%) in the ADM arm, the implant was removed. Four of the removals took place within 6 months after early surgical complications. In the control group, seven patients (11%) underwent implant removal; four were removed within 6 months, owing to early surgical complications.
The secondary endpoint was postoperative health-related quality of life, including perception of body image and satisfaction with cosmetic outcome. There were no significant differences between the two groups.
Some questions remain
Approached for comment on the study, Sameer A. Patel, MD, FACS, chief of plastic and reconstructive surgery at Fox Chase Cancer Center, Philadelphia, noted that the practice of using AMD for breast reconstruction is quite common in the United States, so these data are informative and add to the current understanding of the value of ADM in breast reconstruction. “The study hypothesized that the use of ADM would reduce the number of reoperations within the first 24 months, which it did not,” he said. “This is despite the fact that the ADM group had a significantly higher number of direct-to-implant reconstructions.”
Importantly, the study showed that patient-reported outcomes, as opposed to surgeon’s evaluation of outcomes, were also not different for the most part between the two groups, Dr. Patel pointed out. “The only exception of small favorable advantage in the ADM group was for fitting bras,” he said.
However, there were limitations to the study’s endpoint. “I would add that there are some purported advantages of using ADM, such as reduction in postoperative pain and reduction in length of hospital stay, which are not evaluated by this study,” Patel explained. “Also, I am not certain that they can conclude from this study that capsular contracture is not reduced, because it is not designed to evaluate that.”
But the biggest limitation is one that study authors point out in their discussion at the end of the article, he added. “The use of prepectoral reconstruction is rapidly replacing the dual plane reconstruction that this paper used in the ADM group,” Dr. Patel said. “The role of ADM in prepectoral reconstruction is somewhat different than in the dual plane reconstruction, and so these results may not necessarily be extrapolated to prepectoral reconstruction.”
The study was funded with grants from the Swedish Breast Cancer Association and Stockholm City Council. The trial was initiated by Karolinska University Hospital and Karolinska Institutet. Acelity (an Allergan company) supplied the study with acellular dermal matrix meshes. Dr. Lohmander and Dr. Patel have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A European study involving 155 women found that the use of acellular dermal matrix (ADM) did not lead to fewer reoperations, nor was it superior in terms of health-related quality of life or patient-reported cosmetic outcomes.
“We feel that women considering implant-based reconstructions for breast cancer should be informed about the lack of evidence supporting its advantage,” said lead author Fredrik Lohmander MD, department of breast and endocrine surgery, section of breast urgery, Karolinska University Hospital, Stockholm.
It is difficult to say generally whether ADM should be used in IBBR, he noted. “We can only conclude from our trial that there is no hard evidence that ADM is beneficial when performing breast reconstructions with implants,” he said in an interview. “In selected patients, ADM might be indicated.”
The study was conducted in Sweden and the United Kingdom. “Mostly because of high costs, ADM in implant-based breast reconstructions in Sweden is not frequently used,” Dr. Lohmander said. “It is slightly more common in the U.K., but much more common in the U.S.A.”
Although biological meshes have received regulatory approval by the U.S. Food and Drug Administration for reconstructive purposes, ADM has not been approved for use in breast reconstruction surgery, and its use in this setting is off label.
The study was published online October 1 in JAMA Network Open.
Any advantage to using mesh device?
Previous studies of ADMs suggested that the mesh device conferred several benefits, including superior cosmetic results, less need for tissue expanders, fewer elective reoperations, and less capsular contracture. The use of a mesh device also enlarges the subpectoral pocket, which allows for larger fixed-volume implants, the authors note.
However, these suggested advantages have not been universally accepted, and the authors note that there have been reports of associated harm, such as higher rates of infection and implant loss.
The new study included 135 women from five centers in Sweden and the United Kingdom. The patients had breast cancer and had planned to undergo mastectomy and immediate IBBR between 2014 and May 2017.
The primary endpoint was the number of repeat surgeries at 2 years.
At the 2-year follow-up, 31 patients (48%) in the ADM group had undergone at least one reoperation on the ipsilateral side, vs 35 (54%) in the control group (P = .54). Results were similar for the contralateral side: 34 (53%) vs 31 (48%).
Two patients in the ADM group and three patients in the control group underwent a risk-reducing mastectomy on the contralateral side. These five surgeries were included in the final analysis.
For nine patients (14%) in the ADM arm, the implant was removed. Four of the removals took place within 6 months after early surgical complications. In the control group, seven patients (11%) underwent implant removal; four were removed within 6 months, owing to early surgical complications.
The secondary endpoint was postoperative health-related quality of life, including perception of body image and satisfaction with cosmetic outcome. There were no significant differences between the two groups.
Some questions remain
Approached for comment on the study, Sameer A. Patel, MD, FACS, chief of plastic and reconstructive surgery at Fox Chase Cancer Center, Philadelphia, noted that the practice of using AMD for breast reconstruction is quite common in the United States, so these data are informative and add to the current understanding of the value of ADM in breast reconstruction. “The study hypothesized that the use of ADM would reduce the number of reoperations within the first 24 months, which it did not,” he said. “This is despite the fact that the ADM group had a significantly higher number of direct-to-implant reconstructions.”
Importantly, the study showed that patient-reported outcomes, as opposed to surgeon’s evaluation of outcomes, were also not different for the most part between the two groups, Dr. Patel pointed out. “The only exception of small favorable advantage in the ADM group was for fitting bras,” he said.
However, there were limitations to the study’s endpoint. “I would add that there are some purported advantages of using ADM, such as reduction in postoperative pain and reduction in length of hospital stay, which are not evaluated by this study,” Patel explained. “Also, I am not certain that they can conclude from this study that capsular contracture is not reduced, because it is not designed to evaluate that.”
But the biggest limitation is one that study authors point out in their discussion at the end of the article, he added. “The use of prepectoral reconstruction is rapidly replacing the dual plane reconstruction that this paper used in the ADM group,” Dr. Patel said. “The role of ADM in prepectoral reconstruction is somewhat different than in the dual plane reconstruction, and so these results may not necessarily be extrapolated to prepectoral reconstruction.”
The study was funded with grants from the Swedish Breast Cancer Association and Stockholm City Council. The trial was initiated by Karolinska University Hospital and Karolinska Institutet. Acelity (an Allergan company) supplied the study with acellular dermal matrix meshes. Dr. Lohmander and Dr. Patel have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Case report: Lung cancer shrinks in patient using CBD oil
A case report describes the dramatic shrinkage of a tumor to a quarter of its original size in a patient with non–small cell lung cancer (NSCLC) who had declined conventional treatment, continued smoking, and who later revealed that she was ingesting cannabidiol (CBD) oil.
The patient was an 80-year-old woman.
At diagnosis, the tumor measured 41 mm, and there was no evidence of local or further spread. Hence, it was suitable for a standard treatment regimen of surgery, chemotherapy, and radiotherapy, note the authors.
The patient declined conventional treatment. She underwent monitoring with regular CT scans every 3–6 months.
After 2.5 years, the CT scans showed that the tumor had shrunk to 10 mm.
It was taken orally about two to three times a day.
Details of the case were published on October 14 in BMJ Case Reports.
“We are aware of the limitations of this case report,” write the authors, led by Kah Ling Liew, MD, of Watford General Hospital, Watford, United Kingdom.
“Although there appears to be a relationship between the intake of ‘CBD oil’ and the observed tumour regression, we are unable to conclusively confirm that the tumour regression is due to the patient taking ‘CBD oil,’ ” they comment.
The team also notes that there are similar case reports in the medical literature.
Both points were emphasized by experts reacting to the publication via the UK Science Media Center.
“This is one of many such promising single case reports of medical cannabis self-treatment for various cancers,” said David Nutt, DM, FRCP, FRCPsych, the Edmond J. Safra Chair in Neuropsychopharmacology, Imperial College London, United Kingdom. “Such case reports are biologically credible given the adaptogenic nature of the endocannabinoid system.”
He noted that a “case report itself is not sufficient to give any form of proof that one thing caused the other -- we need trials for that. There are some controlled trials already started and more are required to properly explore the potential of medical cannabis in a range of cancers.”
Another expert, Edzard Ernst, MD, PhD, professor emeritus of complementary medicine, University of Exeter, United Kingdom, pointed out that in animal models, cannabinoids have reduced the size of prostate cancer tumors. “Previous case reports have yielded encouraging findings also in human cancers,” he noted. He too said that further study is needed.
“Case reports cannot be considered to be reliable evidence, and there are currently no data from rigorous clinical trials to suggest that cannabis products will alter the natural history of any cancer,”Dr. Ernst said.
Patient declined recommended treatment
The patient initially presented with a persistent cough that did not resolve with antibiotic therapy. She has a history of mild chronic obstructive pulmonary disease, osteoarthritis, and hypertension. She is a current smoker with a 68 pack-year history of smoking. She has no history of alcohol consumption and is taking several prescription medications.
After an initial CT scan, she underwent a CT-guided lung biopsy and was diagnosed with NSCLC (TNM stage T2bN0Mx). Further analysis of the tumor tissue showed that it was negative for ALK and EGFR mutations. PDL1 was expressed by <1% of the tumor cells. No distant metastases were detected.
A subsequent CT scan revealed that the main tumor in her right middle lobe had shrunk from 41 mm to 33 mm. There were new bilateral upper lobe nodules, one in the left apex, which measured 4 mm, and one in right apex, which measured 6 mm.
The patient was referred to cardiothoracic surgeons for a possible lobectomy, but the patient declined to have surgery. She was then referred to the oncologists. She underwent repeat CT and positron-emission tomography (PET) scans, which showed that her cancer had continued to shrink. On CT, there was an 11-mm reduction, and on PET, an 18-mm reduction. The left apical nodule had resolved, and the right upper lobe nodule was reduced in size.
The patient was offered stereotactic ablative radiotherapy, but she declined this treatment. Because she had refused all standard therapies, a decision was made to “watch and wait.” The patient underwent regular CT surveillance.
Over the course of 2.5 years, the tumor continued to regress. By February 2021, it had shrunk to 10 mm, which represents an overall reduction of 76% in maximum axial diameter. The average rate of reduction was 2.4% per month throughout the monitoring period.
“This case was brought to the attention of the local lung MDT [multidisciplinary team] in February 2019 when the serial imaging showed a reduction in tumor size despite having received no conventional treatment for her lung cancer,” write the authors.
The patient was contacted to discuss her results. She revealed that she was using CBD oil and that she had started taking it in August 2018. No changes had been made in her prescription medications, diet, and lifestyle, and she continued to smoke a pack of cigarettes every week.
“I was not very interested in traditional cancer treatments,” the patient said, “as I was worried about the risks of surgery, and I saw my late husband suffer through the side effects of radiotherapy. My relative suggested that I should try ‘cannabidiol (CBD) oil’ to treat my cancer, and I have been taking it regularly ever since. I am ‘over the moon’ with my cancer shrinking, which I believe was caused by the ‘CBD oil’. I am tolerating it very well and I intend to take this treatment indefinitely.”
The source of the CBD oil was outside the United Kingdom. The main active ingredients, according to her supplier, were Δ9-tetrahydrocannabinol (THC), at 19.5%, CBD, at 20.05%, and tetrahydrocannabinolic acid, at 23.8%.
“The product used by this patient reportedly contained high levels of THC (the intoxicating component of cannabis) and was sourced from outside the U.K.,” commented Tom Freeman, PhD, senior lecturer and director of the Addiction and Mental Health Group, University of Bath, United Kingdom. “This type of product is very different to most CBD oils, which predominantly contain CBD. Unlike prescribed medicines, CBD wellness products lack assurance of quality, safety, or efficacy and should not be used for medicinal purposes.”
The authors have disclosed no relevant financial relationships. Dr. Nutt chairs the scientific committee of the charity Drug Science, which receives unrestricted educational grants from some medical cannabis companies. Dr. Ernst and Dr. Freeman have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A case report describes the dramatic shrinkage of a tumor to a quarter of its original size in a patient with non–small cell lung cancer (NSCLC) who had declined conventional treatment, continued smoking, and who later revealed that she was ingesting cannabidiol (CBD) oil.
The patient was an 80-year-old woman.
At diagnosis, the tumor measured 41 mm, and there was no evidence of local or further spread. Hence, it was suitable for a standard treatment regimen of surgery, chemotherapy, and radiotherapy, note the authors.
The patient declined conventional treatment. She underwent monitoring with regular CT scans every 3–6 months.
After 2.5 years, the CT scans showed that the tumor had shrunk to 10 mm.
It was taken orally about two to three times a day.
Details of the case were published on October 14 in BMJ Case Reports.
“We are aware of the limitations of this case report,” write the authors, led by Kah Ling Liew, MD, of Watford General Hospital, Watford, United Kingdom.
“Although there appears to be a relationship between the intake of ‘CBD oil’ and the observed tumour regression, we are unable to conclusively confirm that the tumour regression is due to the patient taking ‘CBD oil,’ ” they comment.
The team also notes that there are similar case reports in the medical literature.
Both points were emphasized by experts reacting to the publication via the UK Science Media Center.
“This is one of many such promising single case reports of medical cannabis self-treatment for various cancers,” said David Nutt, DM, FRCP, FRCPsych, the Edmond J. Safra Chair in Neuropsychopharmacology, Imperial College London, United Kingdom. “Such case reports are biologically credible given the adaptogenic nature of the endocannabinoid system.”
He noted that a “case report itself is not sufficient to give any form of proof that one thing caused the other -- we need trials for that. There are some controlled trials already started and more are required to properly explore the potential of medical cannabis in a range of cancers.”
Another expert, Edzard Ernst, MD, PhD, professor emeritus of complementary medicine, University of Exeter, United Kingdom, pointed out that in animal models, cannabinoids have reduced the size of prostate cancer tumors. “Previous case reports have yielded encouraging findings also in human cancers,” he noted. He too said that further study is needed.
“Case reports cannot be considered to be reliable evidence, and there are currently no data from rigorous clinical trials to suggest that cannabis products will alter the natural history of any cancer,”Dr. Ernst said.
Patient declined recommended treatment
The patient initially presented with a persistent cough that did not resolve with antibiotic therapy. She has a history of mild chronic obstructive pulmonary disease, osteoarthritis, and hypertension. She is a current smoker with a 68 pack-year history of smoking. She has no history of alcohol consumption and is taking several prescription medications.
After an initial CT scan, she underwent a CT-guided lung biopsy and was diagnosed with NSCLC (TNM stage T2bN0Mx). Further analysis of the tumor tissue showed that it was negative for ALK and EGFR mutations. PDL1 was expressed by <1% of the tumor cells. No distant metastases were detected.
A subsequent CT scan revealed that the main tumor in her right middle lobe had shrunk from 41 mm to 33 mm. There were new bilateral upper lobe nodules, one in the left apex, which measured 4 mm, and one in right apex, which measured 6 mm.
The patient was referred to cardiothoracic surgeons for a possible lobectomy, but the patient declined to have surgery. She was then referred to the oncologists. She underwent repeat CT and positron-emission tomography (PET) scans, which showed that her cancer had continued to shrink. On CT, there was an 11-mm reduction, and on PET, an 18-mm reduction. The left apical nodule had resolved, and the right upper lobe nodule was reduced in size.
The patient was offered stereotactic ablative radiotherapy, but she declined this treatment. Because she had refused all standard therapies, a decision was made to “watch and wait.” The patient underwent regular CT surveillance.
Over the course of 2.5 years, the tumor continued to regress. By February 2021, it had shrunk to 10 mm, which represents an overall reduction of 76% in maximum axial diameter. The average rate of reduction was 2.4% per month throughout the monitoring period.
“This case was brought to the attention of the local lung MDT [multidisciplinary team] in February 2019 when the serial imaging showed a reduction in tumor size despite having received no conventional treatment for her lung cancer,” write the authors.
The patient was contacted to discuss her results. She revealed that she was using CBD oil and that she had started taking it in August 2018. No changes had been made in her prescription medications, diet, and lifestyle, and she continued to smoke a pack of cigarettes every week.
“I was not very interested in traditional cancer treatments,” the patient said, “as I was worried about the risks of surgery, and I saw my late husband suffer through the side effects of radiotherapy. My relative suggested that I should try ‘cannabidiol (CBD) oil’ to treat my cancer, and I have been taking it regularly ever since. I am ‘over the moon’ with my cancer shrinking, which I believe was caused by the ‘CBD oil’. I am tolerating it very well and I intend to take this treatment indefinitely.”
The source of the CBD oil was outside the United Kingdom. The main active ingredients, according to her supplier, were Δ9-tetrahydrocannabinol (THC), at 19.5%, CBD, at 20.05%, and tetrahydrocannabinolic acid, at 23.8%.
“The product used by this patient reportedly contained high levels of THC (the intoxicating component of cannabis) and was sourced from outside the U.K.,” commented Tom Freeman, PhD, senior lecturer and director of the Addiction and Mental Health Group, University of Bath, United Kingdom. “This type of product is very different to most CBD oils, which predominantly contain CBD. Unlike prescribed medicines, CBD wellness products lack assurance of quality, safety, or efficacy and should not be used for medicinal purposes.”
The authors have disclosed no relevant financial relationships. Dr. Nutt chairs the scientific committee of the charity Drug Science, which receives unrestricted educational grants from some medical cannabis companies. Dr. Ernst and Dr. Freeman have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A case report describes the dramatic shrinkage of a tumor to a quarter of its original size in a patient with non–small cell lung cancer (NSCLC) who had declined conventional treatment, continued smoking, and who later revealed that she was ingesting cannabidiol (CBD) oil.
The patient was an 80-year-old woman.
At diagnosis, the tumor measured 41 mm, and there was no evidence of local or further spread. Hence, it was suitable for a standard treatment regimen of surgery, chemotherapy, and radiotherapy, note the authors.
The patient declined conventional treatment. She underwent monitoring with regular CT scans every 3–6 months.
After 2.5 years, the CT scans showed that the tumor had shrunk to 10 mm.
It was taken orally about two to three times a day.
Details of the case were published on October 14 in BMJ Case Reports.
“We are aware of the limitations of this case report,” write the authors, led by Kah Ling Liew, MD, of Watford General Hospital, Watford, United Kingdom.
“Although there appears to be a relationship between the intake of ‘CBD oil’ and the observed tumour regression, we are unable to conclusively confirm that the tumour regression is due to the patient taking ‘CBD oil,’ ” they comment.
The team also notes that there are similar case reports in the medical literature.
Both points were emphasized by experts reacting to the publication via the UK Science Media Center.
“This is one of many such promising single case reports of medical cannabis self-treatment for various cancers,” said David Nutt, DM, FRCP, FRCPsych, the Edmond J. Safra Chair in Neuropsychopharmacology, Imperial College London, United Kingdom. “Such case reports are biologically credible given the adaptogenic nature of the endocannabinoid system.”
He noted that a “case report itself is not sufficient to give any form of proof that one thing caused the other -- we need trials for that. There are some controlled trials already started and more are required to properly explore the potential of medical cannabis in a range of cancers.”
Another expert, Edzard Ernst, MD, PhD, professor emeritus of complementary medicine, University of Exeter, United Kingdom, pointed out that in animal models, cannabinoids have reduced the size of prostate cancer tumors. “Previous case reports have yielded encouraging findings also in human cancers,” he noted. He too said that further study is needed.
“Case reports cannot be considered to be reliable evidence, and there are currently no data from rigorous clinical trials to suggest that cannabis products will alter the natural history of any cancer,”Dr. Ernst said.
Patient declined recommended treatment
The patient initially presented with a persistent cough that did not resolve with antibiotic therapy. She has a history of mild chronic obstructive pulmonary disease, osteoarthritis, and hypertension. She is a current smoker with a 68 pack-year history of smoking. She has no history of alcohol consumption and is taking several prescription medications.
After an initial CT scan, she underwent a CT-guided lung biopsy and was diagnosed with NSCLC (TNM stage T2bN0Mx). Further analysis of the tumor tissue showed that it was negative for ALK and EGFR mutations. PDL1 was expressed by <1% of the tumor cells. No distant metastases were detected.
A subsequent CT scan revealed that the main tumor in her right middle lobe had shrunk from 41 mm to 33 mm. There were new bilateral upper lobe nodules, one in the left apex, which measured 4 mm, and one in right apex, which measured 6 mm.
The patient was referred to cardiothoracic surgeons for a possible lobectomy, but the patient declined to have surgery. She was then referred to the oncologists. She underwent repeat CT and positron-emission tomography (PET) scans, which showed that her cancer had continued to shrink. On CT, there was an 11-mm reduction, and on PET, an 18-mm reduction. The left apical nodule had resolved, and the right upper lobe nodule was reduced in size.
The patient was offered stereotactic ablative radiotherapy, but she declined this treatment. Because she had refused all standard therapies, a decision was made to “watch and wait.” The patient underwent regular CT surveillance.
Over the course of 2.5 years, the tumor continued to regress. By February 2021, it had shrunk to 10 mm, which represents an overall reduction of 76% in maximum axial diameter. The average rate of reduction was 2.4% per month throughout the monitoring period.
“This case was brought to the attention of the local lung MDT [multidisciplinary team] in February 2019 when the serial imaging showed a reduction in tumor size despite having received no conventional treatment for her lung cancer,” write the authors.
The patient was contacted to discuss her results. She revealed that she was using CBD oil and that she had started taking it in August 2018. No changes had been made in her prescription medications, diet, and lifestyle, and she continued to smoke a pack of cigarettes every week.
“I was not very interested in traditional cancer treatments,” the patient said, “as I was worried about the risks of surgery, and I saw my late husband suffer through the side effects of radiotherapy. My relative suggested that I should try ‘cannabidiol (CBD) oil’ to treat my cancer, and I have been taking it regularly ever since. I am ‘over the moon’ with my cancer shrinking, which I believe was caused by the ‘CBD oil’. I am tolerating it very well and I intend to take this treatment indefinitely.”
The source of the CBD oil was outside the United Kingdom. The main active ingredients, according to her supplier, were Δ9-tetrahydrocannabinol (THC), at 19.5%, CBD, at 20.05%, and tetrahydrocannabinolic acid, at 23.8%.
“The product used by this patient reportedly contained high levels of THC (the intoxicating component of cannabis) and was sourced from outside the U.K.,” commented Tom Freeman, PhD, senior lecturer and director of the Addiction and Mental Health Group, University of Bath, United Kingdom. “This type of product is very different to most CBD oils, which predominantly contain CBD. Unlike prescribed medicines, CBD wellness products lack assurance of quality, safety, or efficacy and should not be used for medicinal purposes.”
The authors have disclosed no relevant financial relationships. Dr. Nutt chairs the scientific committee of the charity Drug Science, which receives unrestricted educational grants from some medical cannabis companies. Dr. Ernst and Dr. Freeman have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Failure to communicate ‘doc-to-doc’ blamed for patient’s death
alleging that his death would have been avoided had there been better communication between the surgical oncologist and the treatment team.
The patient was a 49-year-old man who was experiencing chronic pain in his right ear. He saw a local ear, nose, and throat specialist, who could find no apparent cause after conducting a physical exam.
A CT scan revealed a 1.4-cm mass in the right pharyngeal space. A 1.6-cm lymph node in the right retropharyngeal/parapharyngeal carotid space was affected.
The following week, the patient underwent a positron-emission tomography scan and was subsequently referred to a head and neck surgical oncologist.
The surgeon performed a right radical tonsillectomy and pharyngectomy. During the surgery, the patient experienced significant bleeding complications. The surgeon was able to remove the tonsillar mass but could not resect the affected lymph node, owing to its proximity to the carotid artery. The affected lymph node was not removed, and the patient was informed that the problem would be addressed at another time.
Pathology revealed stage III squamous cell carcinoma (T3N0M0) that was HPV/p16 positive.
According to the lawsuit, which was reported in Expert Witness Newsletter, a critical error occurred.
The surgical oncologist apparently did not clearly communicate the situation to the rest of the clinicians involved in the patient’s care. The patient was treated as if the entire cancer had been surgically resected. He never underwent follow-up surgery to address the enlarged lymph node.
Because the care team believed that the patient had undergone a complete surgical resection, follow-up treatment consisted of radiotherapy without concurrent chemotherapy.
The patient underwent radiotherapy to a dose of 60 Gy over 30 treatment days.
About 5 months later, the patient once again presented with ear pain on the right side and difficulty speaking. Imaging showed that there was recurrence of a mass in his right parapharyngeal carotid space. Biopsy results indicated recurrent/progressive squamous cell carcinoma. The patient underwent a second round of radiotherapy. This time, he received concurrent chemotherapy.
Four months later, the patient presented to the emergency department complaining of episodes of syncope. Imaging revealed that the mass in his right parapharyngeal carotid space had increased in size, causing carotid stenosis. The patient was hospitalized for 4 days and was treated with steroids. The day after his discharge, he died at home.
Carotid blowout syndrome due to negligence
An autopsy was performed, and the cause of death was determined to be an acute massive bleed secondary to perforation of the right artery, which was “encased by a partially necrotic poorly differentiated squamous cell carcinoma.” This is known as carotid blowout syndrome.
After his death, the patient’s family contacted an attorney, who hired several expert witnesses to review the case. The alleged negligence by the head and neck oncologist was described as follows:
- There was a failure to appropriately assess the patient’s neck anatomy, and the entire tumor was not surgically removed.
- Frank disease tissue was left behind, and the disease subsequently progressed.
- The surgery was never completed; the cancer progressed and ultimately took the patient’s life.
- There was a failure to communicate the fact that the cancer had not been completely resected.
The alleged negligence by the radiation oncologist was described as follows:
- There was a failure to realize that the tumor had not been completely resected.
- The patient was given a suboptimal radiation dose of 60 Gy, which would have been appropriate only had the tumor been completely resected.
- There was a failure to give a radiation dose of 70 Gy (ie, the appropriate dose for remaining tumor).
The medical oncologist was alleged to have been negligent because chemotherapy was not given when indicated.
Very high stakes
None of the treating physicians were named in the lawsuit. Only the medical center where the treatment was given was named. The center is affiliated with an Ivy League university.
The patient was an extremely wealthy man who had worked as an insurance executive and investor. His premature death resulted in the loss of a massive amount of earnings, and the plaintiffs asked for a sum of $34 million as compensation. Because doctors do not carry insurance sufficient to cover that amount and generally do not have personal assets of that amount, the plaintiff targeted the hospital.
“The plaintiff knows that the physicians will never be able to pay an 8-figure settlement, so instead they go after the hospital itself,” says the newsletter. “The physicians simply become pawns in a protracted legal game.”
The lawsuit was settled out of court in 2021 for an undisclosed amount.
A version of this article first appeared on Medscape.com.
alleging that his death would have been avoided had there been better communication between the surgical oncologist and the treatment team.
The patient was a 49-year-old man who was experiencing chronic pain in his right ear. He saw a local ear, nose, and throat specialist, who could find no apparent cause after conducting a physical exam.
A CT scan revealed a 1.4-cm mass in the right pharyngeal space. A 1.6-cm lymph node in the right retropharyngeal/parapharyngeal carotid space was affected.
The following week, the patient underwent a positron-emission tomography scan and was subsequently referred to a head and neck surgical oncologist.
The surgeon performed a right radical tonsillectomy and pharyngectomy. During the surgery, the patient experienced significant bleeding complications. The surgeon was able to remove the tonsillar mass but could not resect the affected lymph node, owing to its proximity to the carotid artery. The affected lymph node was not removed, and the patient was informed that the problem would be addressed at another time.
Pathology revealed stage III squamous cell carcinoma (T3N0M0) that was HPV/p16 positive.
According to the lawsuit, which was reported in Expert Witness Newsletter, a critical error occurred.
The surgical oncologist apparently did not clearly communicate the situation to the rest of the clinicians involved in the patient’s care. The patient was treated as if the entire cancer had been surgically resected. He never underwent follow-up surgery to address the enlarged lymph node.
Because the care team believed that the patient had undergone a complete surgical resection, follow-up treatment consisted of radiotherapy without concurrent chemotherapy.
The patient underwent radiotherapy to a dose of 60 Gy over 30 treatment days.
About 5 months later, the patient once again presented with ear pain on the right side and difficulty speaking. Imaging showed that there was recurrence of a mass in his right parapharyngeal carotid space. Biopsy results indicated recurrent/progressive squamous cell carcinoma. The patient underwent a second round of radiotherapy. This time, he received concurrent chemotherapy.
Four months later, the patient presented to the emergency department complaining of episodes of syncope. Imaging revealed that the mass in his right parapharyngeal carotid space had increased in size, causing carotid stenosis. The patient was hospitalized for 4 days and was treated with steroids. The day after his discharge, he died at home.
Carotid blowout syndrome due to negligence
An autopsy was performed, and the cause of death was determined to be an acute massive bleed secondary to perforation of the right artery, which was “encased by a partially necrotic poorly differentiated squamous cell carcinoma.” This is known as carotid blowout syndrome.
After his death, the patient’s family contacted an attorney, who hired several expert witnesses to review the case. The alleged negligence by the head and neck oncologist was described as follows:
- There was a failure to appropriately assess the patient’s neck anatomy, and the entire tumor was not surgically removed.
- Frank disease tissue was left behind, and the disease subsequently progressed.
- The surgery was never completed; the cancer progressed and ultimately took the patient’s life.
- There was a failure to communicate the fact that the cancer had not been completely resected.
The alleged negligence by the radiation oncologist was described as follows:
- There was a failure to realize that the tumor had not been completely resected.
- The patient was given a suboptimal radiation dose of 60 Gy, which would have been appropriate only had the tumor been completely resected.
- There was a failure to give a radiation dose of 70 Gy (ie, the appropriate dose for remaining tumor).
The medical oncologist was alleged to have been negligent because chemotherapy was not given when indicated.
Very high stakes
None of the treating physicians were named in the lawsuit. Only the medical center where the treatment was given was named. The center is affiliated with an Ivy League university.
The patient was an extremely wealthy man who had worked as an insurance executive and investor. His premature death resulted in the loss of a massive amount of earnings, and the plaintiffs asked for a sum of $34 million as compensation. Because doctors do not carry insurance sufficient to cover that amount and generally do not have personal assets of that amount, the plaintiff targeted the hospital.
“The plaintiff knows that the physicians will never be able to pay an 8-figure settlement, so instead they go after the hospital itself,” says the newsletter. “The physicians simply become pawns in a protracted legal game.”
The lawsuit was settled out of court in 2021 for an undisclosed amount.
A version of this article first appeared on Medscape.com.
alleging that his death would have been avoided had there been better communication between the surgical oncologist and the treatment team.
The patient was a 49-year-old man who was experiencing chronic pain in his right ear. He saw a local ear, nose, and throat specialist, who could find no apparent cause after conducting a physical exam.
A CT scan revealed a 1.4-cm mass in the right pharyngeal space. A 1.6-cm lymph node in the right retropharyngeal/parapharyngeal carotid space was affected.
The following week, the patient underwent a positron-emission tomography scan and was subsequently referred to a head and neck surgical oncologist.
The surgeon performed a right radical tonsillectomy and pharyngectomy. During the surgery, the patient experienced significant bleeding complications. The surgeon was able to remove the tonsillar mass but could not resect the affected lymph node, owing to its proximity to the carotid artery. The affected lymph node was not removed, and the patient was informed that the problem would be addressed at another time.
Pathology revealed stage III squamous cell carcinoma (T3N0M0) that was HPV/p16 positive.
According to the lawsuit, which was reported in Expert Witness Newsletter, a critical error occurred.
The surgical oncologist apparently did not clearly communicate the situation to the rest of the clinicians involved in the patient’s care. The patient was treated as if the entire cancer had been surgically resected. He never underwent follow-up surgery to address the enlarged lymph node.
Because the care team believed that the patient had undergone a complete surgical resection, follow-up treatment consisted of radiotherapy without concurrent chemotherapy.
The patient underwent radiotherapy to a dose of 60 Gy over 30 treatment days.
About 5 months later, the patient once again presented with ear pain on the right side and difficulty speaking. Imaging showed that there was recurrence of a mass in his right parapharyngeal carotid space. Biopsy results indicated recurrent/progressive squamous cell carcinoma. The patient underwent a second round of radiotherapy. This time, he received concurrent chemotherapy.
Four months later, the patient presented to the emergency department complaining of episodes of syncope. Imaging revealed that the mass in his right parapharyngeal carotid space had increased in size, causing carotid stenosis. The patient was hospitalized for 4 days and was treated with steroids. The day after his discharge, he died at home.
Carotid blowout syndrome due to negligence
An autopsy was performed, and the cause of death was determined to be an acute massive bleed secondary to perforation of the right artery, which was “encased by a partially necrotic poorly differentiated squamous cell carcinoma.” This is known as carotid blowout syndrome.
After his death, the patient’s family contacted an attorney, who hired several expert witnesses to review the case. The alleged negligence by the head and neck oncologist was described as follows:
- There was a failure to appropriately assess the patient’s neck anatomy, and the entire tumor was not surgically removed.
- Frank disease tissue was left behind, and the disease subsequently progressed.
- The surgery was never completed; the cancer progressed and ultimately took the patient’s life.
- There was a failure to communicate the fact that the cancer had not been completely resected.
The alleged negligence by the radiation oncologist was described as follows:
- There was a failure to realize that the tumor had not been completely resected.
- The patient was given a suboptimal radiation dose of 60 Gy, which would have been appropriate only had the tumor been completely resected.
- There was a failure to give a radiation dose of 70 Gy (ie, the appropriate dose for remaining tumor).
The medical oncologist was alleged to have been negligent because chemotherapy was not given when indicated.
Very high stakes
None of the treating physicians were named in the lawsuit. Only the medical center where the treatment was given was named. The center is affiliated with an Ivy League university.
The patient was an extremely wealthy man who had worked as an insurance executive and investor. His premature death resulted in the loss of a massive amount of earnings, and the plaintiffs asked for a sum of $34 million as compensation. Because doctors do not carry insurance sufficient to cover that amount and generally do not have personal assets of that amount, the plaintiff targeted the hospital.
“The plaintiff knows that the physicians will never be able to pay an 8-figure settlement, so instead they go after the hospital itself,” says the newsletter. “The physicians simply become pawns in a protracted legal game.”
The lawsuit was settled out of court in 2021 for an undisclosed amount.
A version of this article first appeared on Medscape.com.
‘Regionalized’ care tied to better survival in tough cancer
The Kaiser Permanente Northern California (KPNC) Gastric-Esophageal Cancer Program was established in 2016 to consolidate the care of patients with gastric cancer and increase physician specialization and standardization.
In a retrospective study, Kaiser Permanente investigators compared the outcomes of the 942 patients diagnosed before the regional gastric cancer team was established with the outcomes of the 487 patients treated after it was implemented. Overall, the transformation appears to enhance the delivery of care and improves clinical and oncologic outcomes.
For example, among 394 patients who received curative-intent surgery, overall survival at 2 years increased from 72.7% before the program to 85.5% afterward.
“The regionalized gastric cancer program combines the benefits of community-based care, which is local and convenient, with the expertise of a specialized cancer center,” said coauthor Lisa Herrinton, PhD, a research scientist at the Kaiser Permanente division of research, in a statement.
She added that, in their integrated care system, “it is easy for the different physicians that treat cancer patients – including surgical oncologists, medical oncologists, and radiation oncologists, among others – to come together and collaborate and tie their work flows together.”
The study was published in the Journal of Clinical Oncology.
Gastric cancer accounts for about 27,600 cases diagnosed annually in the United States, but the overall 5-year survival is still only 32%. About half of the cases are locoregional (stage I-III) and potentially eligible for curative-intent surgery and adjuvant therapy, the authors pointed out in the study.
As compared with North America, the incidence rate is five to six times higher in East Asia, but they have developed better surveillance for early detection and treatment is highly effective, as the increased incidence allows oncologists and surgeons to achieve greater specialization. Laparoscopic gastrectomy and extended (D2) lymph node dissection are more commonly performed in East Asia as compared with the United States, and surgical outcomes appear to be better in East Asia.
Regionalizing care
The rationale for regionalizing care was that increasing and concentrating the volume of cases to a specific location would make it more possible to introduce new surgical procedures as well as allow medical oncologists to uniformly introduce and standardize the use of the newest chemotherapy regimens.
Prior to regionalization, gastric cancer surgery was performed at 19 medical centers in the Kaiser system. Now, curative-intent laparoscopic gastrectomy with Roux-en-Y gastrojejunostomy or esophagojejunostomy and side-to-side jejunojejunostomy is subsequently performed at only two centers by five surgeons.
“The two centers were selected based on how skilled the surgeons were at performing advanced minimally invasive oncologic surgery,” said lead author Swee H. Teh, MD, surgical director, gastric cancer surgery, Kaiser Permanente Northern California. “We also looked at the center’s retrospective gastrectomy outcomes and the strength of the leadership that would be collaborating with the regional multidisciplinary team.”
Dr. Teh said in an interview that it was imperative that their regional gastric cancer centers have surgeons highly skilled in advanced minimally invasive gastrointestinal surgery. “This is a newer technique and not one of our more senior surgeons had been trained in [it],” he said. “With this change, some surgeons were now no longer performing gastric cancer surgery.”
Not only were the centers selected based on the surgical skills of the surgeons already there, but they also took into account the locations and geographical membership distribution. “We have found that our patients’ traveling distance to receive surgical care has not changed significantly,” Dr. Teh said.
Improved outcomes
The cohort included 1,429 eligible patients all stages of gastric cancer; one-third were treated after regionalization, 650 had stage I-III disease, and 394 underwent curative-intent surgery.
Overall survival at 2 years was 32.8% pre- and 37.3% post regionalization (P = .20) for all stages of cancer; stage I-III cases with or without surgery, 55.6% and 61.1%, respectively (P = .25); and among all surgery patients, 72.7% and 85.5%, respectively (P < .03).
Among patients who underwent surgery, the use of neoadjuvant chemotherapy increased from 35% to 66% (P < .0001), as did laparoscopic gastrectomy from 18% to 92% (P < .0001), and D2 lymphadenectomy from 2% to 80% (P < .0001). In addition, dissection of 15 or more lymph nodes also rose from 61% to 95% (P < .0001). Post regionalization, the resection margin was more often negative, and the resection less often involved other organs.
The median length of hospitalization declined from 7 to 3 days (P < .001) after regionalization but all-cause readmissions and reoperation at 30 and 90 days were similar in both cohorts. The risk of bowel obstruction was less frequent post regionalization (P = .01 at both 30 and 90 days), as was risk of infection (P = .03 at 30 days and P = .01 at 90 days).
The risk of one or more serious adverse events was also lower (P < .01), and 30-day mortality did not change (pre 0.7% and post 0.0%, P = .34).
Generalizability may not be feasible
But although this was successful for Kaiser, the authors note that a key limitation of the study is generalizability – and that regionalization may not be feasible in many U.S. settings.
“There needs to be a standardized workflow that all stakeholders agree upon,” Dr. Teh explained. “For example, in our gastric cancer staging pathway, all patients who are considered candidates for surgery have four staging tests: CT scan, PET scan and endoscopic ultrasound [EUS], and staging laparoscopy.”
Another important aspect is that in order to make sure the workflow is smooth and timely, all subspecialties responsible for the staging modalities need to create a “special access.” What this means, he continued, is for example, that the radiology department must ensure that these patients will have their CT scan and PET scans promptly. “Similarly, the GI department must provide quick access to EUS, and the surgery department must quickly provide a staging laparoscopy,” Dr. Teh said. “We have been extremely successful in achieving this goal.”
Dr. Teh also noted that a skilled patient navigator and a team where each member brings high-level expertise and experience to the table are also necessary. And innovative technology is also needed.
“We use artificial intelligence to identify all newly diagnosed cases of gastric [cancer], and within 24 hours of a patient’s diagnosis, a notification is sent to entire team about this new patient,” he added. “We also use AI to extract data to create a dashboard that will track each patient’s progress and outcomes, so that the results are accessible to every member of the team. The innovative technology has also helped us build a comprehensive survivorship program.”
They also noted in their study that European and Canadian systems, as well as the Department of Veterans Affairs, could probably implement components of this, including enhanced recovery after surgery.
The study had no specific funding. Dr. Teh and Dr. Herrinton have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The Kaiser Permanente Northern California (KPNC) Gastric-Esophageal Cancer Program was established in 2016 to consolidate the care of patients with gastric cancer and increase physician specialization and standardization.
In a retrospective study, Kaiser Permanente investigators compared the outcomes of the 942 patients diagnosed before the regional gastric cancer team was established with the outcomes of the 487 patients treated after it was implemented. Overall, the transformation appears to enhance the delivery of care and improves clinical and oncologic outcomes.
For example, among 394 patients who received curative-intent surgery, overall survival at 2 years increased from 72.7% before the program to 85.5% afterward.
“The regionalized gastric cancer program combines the benefits of community-based care, which is local and convenient, with the expertise of a specialized cancer center,” said coauthor Lisa Herrinton, PhD, a research scientist at the Kaiser Permanente division of research, in a statement.
She added that, in their integrated care system, “it is easy for the different physicians that treat cancer patients – including surgical oncologists, medical oncologists, and radiation oncologists, among others – to come together and collaborate and tie their work flows together.”
The study was published in the Journal of Clinical Oncology.
Gastric cancer accounts for about 27,600 cases diagnosed annually in the United States, but the overall 5-year survival is still only 32%. About half of the cases are locoregional (stage I-III) and potentially eligible for curative-intent surgery and adjuvant therapy, the authors pointed out in the study.
As compared with North America, the incidence rate is five to six times higher in East Asia, but they have developed better surveillance for early detection and treatment is highly effective, as the increased incidence allows oncologists and surgeons to achieve greater specialization. Laparoscopic gastrectomy and extended (D2) lymph node dissection are more commonly performed in East Asia as compared with the United States, and surgical outcomes appear to be better in East Asia.
Regionalizing care
The rationale for regionalizing care was that increasing and concentrating the volume of cases to a specific location would make it more possible to introduce new surgical procedures as well as allow medical oncologists to uniformly introduce and standardize the use of the newest chemotherapy regimens.
Prior to regionalization, gastric cancer surgery was performed at 19 medical centers in the Kaiser system. Now, curative-intent laparoscopic gastrectomy with Roux-en-Y gastrojejunostomy or esophagojejunostomy and side-to-side jejunojejunostomy is subsequently performed at only two centers by five surgeons.
“The two centers were selected based on how skilled the surgeons were at performing advanced minimally invasive oncologic surgery,” said lead author Swee H. Teh, MD, surgical director, gastric cancer surgery, Kaiser Permanente Northern California. “We also looked at the center’s retrospective gastrectomy outcomes and the strength of the leadership that would be collaborating with the regional multidisciplinary team.”
Dr. Teh said in an interview that it was imperative that their regional gastric cancer centers have surgeons highly skilled in advanced minimally invasive gastrointestinal surgery. “This is a newer technique and not one of our more senior surgeons had been trained in [it],” he said. “With this change, some surgeons were now no longer performing gastric cancer surgery.”
Not only were the centers selected based on the surgical skills of the surgeons already there, but they also took into account the locations and geographical membership distribution. “We have found that our patients’ traveling distance to receive surgical care has not changed significantly,” Dr. Teh said.
Improved outcomes
The cohort included 1,429 eligible patients all stages of gastric cancer; one-third were treated after regionalization, 650 had stage I-III disease, and 394 underwent curative-intent surgery.
Overall survival at 2 years was 32.8% pre- and 37.3% post regionalization (P = .20) for all stages of cancer; stage I-III cases with or without surgery, 55.6% and 61.1%, respectively (P = .25); and among all surgery patients, 72.7% and 85.5%, respectively (P < .03).
Among patients who underwent surgery, the use of neoadjuvant chemotherapy increased from 35% to 66% (P < .0001), as did laparoscopic gastrectomy from 18% to 92% (P < .0001), and D2 lymphadenectomy from 2% to 80% (P < .0001). In addition, dissection of 15 or more lymph nodes also rose from 61% to 95% (P < .0001). Post regionalization, the resection margin was more often negative, and the resection less often involved other organs.
The median length of hospitalization declined from 7 to 3 days (P < .001) after regionalization but all-cause readmissions and reoperation at 30 and 90 days were similar in both cohorts. The risk of bowel obstruction was less frequent post regionalization (P = .01 at both 30 and 90 days), as was risk of infection (P = .03 at 30 days and P = .01 at 90 days).
The risk of one or more serious adverse events was also lower (P < .01), and 30-day mortality did not change (pre 0.7% and post 0.0%, P = .34).
Generalizability may not be feasible
But although this was successful for Kaiser, the authors note that a key limitation of the study is generalizability – and that regionalization may not be feasible in many U.S. settings.
“There needs to be a standardized workflow that all stakeholders agree upon,” Dr. Teh explained. “For example, in our gastric cancer staging pathway, all patients who are considered candidates for surgery have four staging tests: CT scan, PET scan and endoscopic ultrasound [EUS], and staging laparoscopy.”
Another important aspect is that in order to make sure the workflow is smooth and timely, all subspecialties responsible for the staging modalities need to create a “special access.” What this means, he continued, is for example, that the radiology department must ensure that these patients will have their CT scan and PET scans promptly. “Similarly, the GI department must provide quick access to EUS, and the surgery department must quickly provide a staging laparoscopy,” Dr. Teh said. “We have been extremely successful in achieving this goal.”
Dr. Teh also noted that a skilled patient navigator and a team where each member brings high-level expertise and experience to the table are also necessary. And innovative technology is also needed.
“We use artificial intelligence to identify all newly diagnosed cases of gastric [cancer], and within 24 hours of a patient’s diagnosis, a notification is sent to entire team about this new patient,” he added. “We also use AI to extract data to create a dashboard that will track each patient’s progress and outcomes, so that the results are accessible to every member of the team. The innovative technology has also helped us build a comprehensive survivorship program.”
They also noted in their study that European and Canadian systems, as well as the Department of Veterans Affairs, could probably implement components of this, including enhanced recovery after surgery.
The study had no specific funding. Dr. Teh and Dr. Herrinton have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The Kaiser Permanente Northern California (KPNC) Gastric-Esophageal Cancer Program was established in 2016 to consolidate the care of patients with gastric cancer and increase physician specialization and standardization.
In a retrospective study, Kaiser Permanente investigators compared the outcomes of the 942 patients diagnosed before the regional gastric cancer team was established with the outcomes of the 487 patients treated after it was implemented. Overall, the transformation appears to enhance the delivery of care and improves clinical and oncologic outcomes.
For example, among 394 patients who received curative-intent surgery, overall survival at 2 years increased from 72.7% before the program to 85.5% afterward.
“The regionalized gastric cancer program combines the benefits of community-based care, which is local and convenient, with the expertise of a specialized cancer center,” said coauthor Lisa Herrinton, PhD, a research scientist at the Kaiser Permanente division of research, in a statement.
She added that, in their integrated care system, “it is easy for the different physicians that treat cancer patients – including surgical oncologists, medical oncologists, and radiation oncologists, among others – to come together and collaborate and tie their work flows together.”
The study was published in the Journal of Clinical Oncology.
Gastric cancer accounts for about 27,600 cases diagnosed annually in the United States, but the overall 5-year survival is still only 32%. About half of the cases are locoregional (stage I-III) and potentially eligible for curative-intent surgery and adjuvant therapy, the authors pointed out in the study.
As compared with North America, the incidence rate is five to six times higher in East Asia, but they have developed better surveillance for early detection and treatment is highly effective, as the increased incidence allows oncologists and surgeons to achieve greater specialization. Laparoscopic gastrectomy and extended (D2) lymph node dissection are more commonly performed in East Asia as compared with the United States, and surgical outcomes appear to be better in East Asia.
Regionalizing care
The rationale for regionalizing care was that increasing and concentrating the volume of cases to a specific location would make it more possible to introduce new surgical procedures as well as allow medical oncologists to uniformly introduce and standardize the use of the newest chemotherapy regimens.
Prior to regionalization, gastric cancer surgery was performed at 19 medical centers in the Kaiser system. Now, curative-intent laparoscopic gastrectomy with Roux-en-Y gastrojejunostomy or esophagojejunostomy and side-to-side jejunojejunostomy is subsequently performed at only two centers by five surgeons.
“The two centers were selected based on how skilled the surgeons were at performing advanced minimally invasive oncologic surgery,” said lead author Swee H. Teh, MD, surgical director, gastric cancer surgery, Kaiser Permanente Northern California. “We also looked at the center’s retrospective gastrectomy outcomes and the strength of the leadership that would be collaborating with the regional multidisciplinary team.”
Dr. Teh said in an interview that it was imperative that their regional gastric cancer centers have surgeons highly skilled in advanced minimally invasive gastrointestinal surgery. “This is a newer technique and not one of our more senior surgeons had been trained in [it],” he said. “With this change, some surgeons were now no longer performing gastric cancer surgery.”
Not only were the centers selected based on the surgical skills of the surgeons already there, but they also took into account the locations and geographical membership distribution. “We have found that our patients’ traveling distance to receive surgical care has not changed significantly,” Dr. Teh said.
Improved outcomes
The cohort included 1,429 eligible patients all stages of gastric cancer; one-third were treated after regionalization, 650 had stage I-III disease, and 394 underwent curative-intent surgery.
Overall survival at 2 years was 32.8% pre- and 37.3% post regionalization (P = .20) for all stages of cancer; stage I-III cases with or without surgery, 55.6% and 61.1%, respectively (P = .25); and among all surgery patients, 72.7% and 85.5%, respectively (P < .03).
Among patients who underwent surgery, the use of neoadjuvant chemotherapy increased from 35% to 66% (P < .0001), as did laparoscopic gastrectomy from 18% to 92% (P < .0001), and D2 lymphadenectomy from 2% to 80% (P < .0001). In addition, dissection of 15 or more lymph nodes also rose from 61% to 95% (P < .0001). Post regionalization, the resection margin was more often negative, and the resection less often involved other organs.
The median length of hospitalization declined from 7 to 3 days (P < .001) after regionalization but all-cause readmissions and reoperation at 30 and 90 days were similar in both cohorts. The risk of bowel obstruction was less frequent post regionalization (P = .01 at both 30 and 90 days), as was risk of infection (P = .03 at 30 days and P = .01 at 90 days).
The risk of one or more serious adverse events was also lower (P < .01), and 30-day mortality did not change (pre 0.7% and post 0.0%, P = .34).
Generalizability may not be feasible
But although this was successful for Kaiser, the authors note that a key limitation of the study is generalizability – and that regionalization may not be feasible in many U.S. settings.
“There needs to be a standardized workflow that all stakeholders agree upon,” Dr. Teh explained. “For example, in our gastric cancer staging pathway, all patients who are considered candidates for surgery have four staging tests: CT scan, PET scan and endoscopic ultrasound [EUS], and staging laparoscopy.”
Another important aspect is that in order to make sure the workflow is smooth and timely, all subspecialties responsible for the staging modalities need to create a “special access.” What this means, he continued, is for example, that the radiology department must ensure that these patients will have their CT scan and PET scans promptly. “Similarly, the GI department must provide quick access to EUS, and the surgery department must quickly provide a staging laparoscopy,” Dr. Teh said. “We have been extremely successful in achieving this goal.”
Dr. Teh also noted that a skilled patient navigator and a team where each member brings high-level expertise and experience to the table are also necessary. And innovative technology is also needed.
“We use artificial intelligence to identify all newly diagnosed cases of gastric [cancer], and within 24 hours of a patient’s diagnosis, a notification is sent to entire team about this new patient,” he added. “We also use AI to extract data to create a dashboard that will track each patient’s progress and outcomes, so that the results are accessible to every member of the team. The innovative technology has also helped us build a comprehensive survivorship program.”
They also noted in their study that European and Canadian systems, as well as the Department of Veterans Affairs, could probably implement components of this, including enhanced recovery after surgery.
The study had no specific funding. Dr. Teh and Dr. Herrinton have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FDA approval for tisotumab vedotin in advanced cervical cancer
There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.
In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”
“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.
Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
Details of clinical trial data
The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.
The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.
All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.
The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.
The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.
Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.
Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.
The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
Confirmatory trial underway
Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.
The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.
A version of this article first appeared on Medscape.com.
There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.
In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”
“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.
Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
Details of clinical trial data
The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.
The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.
All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.
The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.
The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.
Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.
Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.
The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
Confirmatory trial underway
Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.
The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.
A version of this article first appeared on Medscape.com.
There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.
In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”
“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.
Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
Details of clinical trial data
The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.
The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.
All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.
The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.
The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.
Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.
Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.
The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
Confirmatory trial underway
Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.
The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.
A version of this article first appeared on Medscape.com.
Severe skin reactions with enfortumab vedotin
The cases came to light during routine surveillance, say staff from the division of pharmacovigilance of the Food and Drug Administration in a research letter published online Sept. 8, 2021, in JAMA Dermatology.
Eight cases of serious skin reactions characterized as SJS/TEN were identified from the FDA’s Adverse Event Reporting System (FAERS). In five of these cases, the diagnosis of SJS/TEN was confirmed by a dermatologist and/or biopsy findings.
The median time to onset of SJS/TEN was 11 days (range, 9-21 days) from the start of treatment.
In the eight cases, serious outcomes were reported. In four cases, deaths that were attributed to SJS/TEN occurred. “Other serious outcomes included admission to the burn unit in four cases,” the researchers wrote.
First-in-class agent
Enfortumab vedotin is a first-in-class agent directed against cell adhesion molecule nectin-4, which is located on the surface of cells and is highly expressed in bladder cancer. The product is an antibody conjugate, in which the antibody directs the product to these cells and then releases the cytoxic monomethyl auristantin E. It is administered intravenously.
The product was granted accelerated approval by the FDA in December 2019. This approval was based on response data from the EV-201 study, a phase 2 clinical trial that involved 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy.
The results were presented in June 2019 at the annual meeting of the American Society of Clinical Oncology. The overall response rate was 44%; 12% of patients achieved a complete response, and 32% had a partial response. The median duration of response was 7.6 months.
At the meeting, Daniel P. Petrylak, MD, professor of medicine (medical oncology) and urology at Yale Cancer Center, New Haven, Conn., noted that there is a “high unmet need” among patients with advanced and metastatic urothelial cancer. There has been a flurry of new drug approvals for this disease. Five immune checkpoint inhibitor drugs have been approved in recent years. Most patients (75%-80%) experience disease progression after receiving immunotherapy.
Enfortumab vedotin is the “first novel therapeutic to demonstrate substantial clinical activity” in patients whose disease has progressed after platinum chemotherapy and immunotherapies, commented Dr. Petrylak.
At the time, maculopapular rash of grade 3 or higher was reported in 4% of the cohort. That was the only serious dermatologic adverse event noted.
Clinically significant findings
The cases of severe skin reactions now being reported come from postmarketing surveillance, noted the authors, led by Michelle Nadeau Nguyen, PharmD, BCOP, BCPS. They reviewed data from FAERS, PubMed, and Embase from Dec. 18, 2019, the date the product was approved, to Oct. 7, 2020.
Other than the eight cases reported to FAERS, no additional cases were identified from PubMed or Embase.
The authors noted that, because cases of SJS/TEN are rare but serious, these well-documented postmarketing reports are clinically significant. “Moreover, we find the rapid accumulation of cases over an approximate 12-month marketing period a concerning observation,” they wrote.
The rate at which these reactions were reported is higher than would be expected, they commented.
The annual incidence of locally advanced urothelial cancer, the disease most likely to be treated with this drug, is around 12,494-40,000 cases per year in the United States. The expected incidence rate of SJS/TEN is about 1-7 cases per 1,000,000 patients. The team calculated from the reports that, among patients who received enfortumab vedotin, the rate was 20 cases per 1,000,000 patients.
This reporting rate is likely to be underestimated, inasmuch as underreporting is known to be a limitation of spontaneous reporting systems such as FAERS, the authors noted.
The mechanism for toxic skin effects with enfortumab vedotin is as yet unknown, but it may be related to the inhibitory effects of the drug on nectin-4 expression, they suggest. Nectin-4 is expressed by epithelial tissues, including skin.
Dr. Nguyen and colleagues noted that, on approval, the U.S. prescribing information for the drug noted that skin reactions were seen in 55% of patients in clinical trials.
The prescribing information was recently revised to include SJS/TEN and to recommend permanent discontinuance of the drug if cases of SJS/TEN are suspected.
“This revision is intended to increase clinicians’ awareness of the risk for SJS/TEN and mitigate serious outcomes by improving the likelihood of early identification and intervention,” they added.
The authors also encouraged continued reporting of adverse events with enfortumab vedotin to the FDA via the MedWatch portal.
The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The cases came to light during routine surveillance, say staff from the division of pharmacovigilance of the Food and Drug Administration in a research letter published online Sept. 8, 2021, in JAMA Dermatology.
Eight cases of serious skin reactions characterized as SJS/TEN were identified from the FDA’s Adverse Event Reporting System (FAERS). In five of these cases, the diagnosis of SJS/TEN was confirmed by a dermatologist and/or biopsy findings.
The median time to onset of SJS/TEN was 11 days (range, 9-21 days) from the start of treatment.
In the eight cases, serious outcomes were reported. In four cases, deaths that were attributed to SJS/TEN occurred. “Other serious outcomes included admission to the burn unit in four cases,” the researchers wrote.
First-in-class agent
Enfortumab vedotin is a first-in-class agent directed against cell adhesion molecule nectin-4, which is located on the surface of cells and is highly expressed in bladder cancer. The product is an antibody conjugate, in which the antibody directs the product to these cells and then releases the cytoxic monomethyl auristantin E. It is administered intravenously.
The product was granted accelerated approval by the FDA in December 2019. This approval was based on response data from the EV-201 study, a phase 2 clinical trial that involved 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy.
The results were presented in June 2019 at the annual meeting of the American Society of Clinical Oncology. The overall response rate was 44%; 12% of patients achieved a complete response, and 32% had a partial response. The median duration of response was 7.6 months.
At the meeting, Daniel P. Petrylak, MD, professor of medicine (medical oncology) and urology at Yale Cancer Center, New Haven, Conn., noted that there is a “high unmet need” among patients with advanced and metastatic urothelial cancer. There has been a flurry of new drug approvals for this disease. Five immune checkpoint inhibitor drugs have been approved in recent years. Most patients (75%-80%) experience disease progression after receiving immunotherapy.
Enfortumab vedotin is the “first novel therapeutic to demonstrate substantial clinical activity” in patients whose disease has progressed after platinum chemotherapy and immunotherapies, commented Dr. Petrylak.
At the time, maculopapular rash of grade 3 or higher was reported in 4% of the cohort. That was the only serious dermatologic adverse event noted.
Clinically significant findings
The cases of severe skin reactions now being reported come from postmarketing surveillance, noted the authors, led by Michelle Nadeau Nguyen, PharmD, BCOP, BCPS. They reviewed data from FAERS, PubMed, and Embase from Dec. 18, 2019, the date the product was approved, to Oct. 7, 2020.
Other than the eight cases reported to FAERS, no additional cases were identified from PubMed or Embase.
The authors noted that, because cases of SJS/TEN are rare but serious, these well-documented postmarketing reports are clinically significant. “Moreover, we find the rapid accumulation of cases over an approximate 12-month marketing period a concerning observation,” they wrote.
The rate at which these reactions were reported is higher than would be expected, they commented.
The annual incidence of locally advanced urothelial cancer, the disease most likely to be treated with this drug, is around 12,494-40,000 cases per year in the United States. The expected incidence rate of SJS/TEN is about 1-7 cases per 1,000,000 patients. The team calculated from the reports that, among patients who received enfortumab vedotin, the rate was 20 cases per 1,000,000 patients.
This reporting rate is likely to be underestimated, inasmuch as underreporting is known to be a limitation of spontaneous reporting systems such as FAERS, the authors noted.
The mechanism for toxic skin effects with enfortumab vedotin is as yet unknown, but it may be related to the inhibitory effects of the drug on nectin-4 expression, they suggest. Nectin-4 is expressed by epithelial tissues, including skin.
Dr. Nguyen and colleagues noted that, on approval, the U.S. prescribing information for the drug noted that skin reactions were seen in 55% of patients in clinical trials.
The prescribing information was recently revised to include SJS/TEN and to recommend permanent discontinuance of the drug if cases of SJS/TEN are suspected.
“This revision is intended to increase clinicians’ awareness of the risk for SJS/TEN and mitigate serious outcomes by improving the likelihood of early identification and intervention,” they added.
The authors also encouraged continued reporting of adverse events with enfortumab vedotin to the FDA via the MedWatch portal.
The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The cases came to light during routine surveillance, say staff from the division of pharmacovigilance of the Food and Drug Administration in a research letter published online Sept. 8, 2021, in JAMA Dermatology.
Eight cases of serious skin reactions characterized as SJS/TEN were identified from the FDA’s Adverse Event Reporting System (FAERS). In five of these cases, the diagnosis of SJS/TEN was confirmed by a dermatologist and/or biopsy findings.
The median time to onset of SJS/TEN was 11 days (range, 9-21 days) from the start of treatment.
In the eight cases, serious outcomes were reported. In four cases, deaths that were attributed to SJS/TEN occurred. “Other serious outcomes included admission to the burn unit in four cases,” the researchers wrote.
First-in-class agent
Enfortumab vedotin is a first-in-class agent directed against cell adhesion molecule nectin-4, which is located on the surface of cells and is highly expressed in bladder cancer. The product is an antibody conjugate, in which the antibody directs the product to these cells and then releases the cytoxic monomethyl auristantin E. It is administered intravenously.
The product was granted accelerated approval by the FDA in December 2019. This approval was based on response data from the EV-201 study, a phase 2 clinical trial that involved 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy.
The results were presented in June 2019 at the annual meeting of the American Society of Clinical Oncology. The overall response rate was 44%; 12% of patients achieved a complete response, and 32% had a partial response. The median duration of response was 7.6 months.
At the meeting, Daniel P. Petrylak, MD, professor of medicine (medical oncology) and urology at Yale Cancer Center, New Haven, Conn., noted that there is a “high unmet need” among patients with advanced and metastatic urothelial cancer. There has been a flurry of new drug approvals for this disease. Five immune checkpoint inhibitor drugs have been approved in recent years. Most patients (75%-80%) experience disease progression after receiving immunotherapy.
Enfortumab vedotin is the “first novel therapeutic to demonstrate substantial clinical activity” in patients whose disease has progressed after platinum chemotherapy and immunotherapies, commented Dr. Petrylak.
At the time, maculopapular rash of grade 3 or higher was reported in 4% of the cohort. That was the only serious dermatologic adverse event noted.
Clinically significant findings
The cases of severe skin reactions now being reported come from postmarketing surveillance, noted the authors, led by Michelle Nadeau Nguyen, PharmD, BCOP, BCPS. They reviewed data from FAERS, PubMed, and Embase from Dec. 18, 2019, the date the product was approved, to Oct. 7, 2020.
Other than the eight cases reported to FAERS, no additional cases were identified from PubMed or Embase.
The authors noted that, because cases of SJS/TEN are rare but serious, these well-documented postmarketing reports are clinically significant. “Moreover, we find the rapid accumulation of cases over an approximate 12-month marketing period a concerning observation,” they wrote.
The rate at which these reactions were reported is higher than would be expected, they commented.
The annual incidence of locally advanced urothelial cancer, the disease most likely to be treated with this drug, is around 12,494-40,000 cases per year in the United States. The expected incidence rate of SJS/TEN is about 1-7 cases per 1,000,000 patients. The team calculated from the reports that, among patients who received enfortumab vedotin, the rate was 20 cases per 1,000,000 patients.
This reporting rate is likely to be underestimated, inasmuch as underreporting is known to be a limitation of spontaneous reporting systems such as FAERS, the authors noted.
The mechanism for toxic skin effects with enfortumab vedotin is as yet unknown, but it may be related to the inhibitory effects of the drug on nectin-4 expression, they suggest. Nectin-4 is expressed by epithelial tissues, including skin.
Dr. Nguyen and colleagues noted that, on approval, the U.S. prescribing information for the drug noted that skin reactions were seen in 55% of patients in clinical trials.
The prescribing information was recently revised to include SJS/TEN and to recommend permanent discontinuance of the drug if cases of SJS/TEN are suspected.
“This revision is intended to increase clinicians’ awareness of the risk for SJS/TEN and mitigate serious outcomes by improving the likelihood of early identification and intervention,” they added.
The authors also encouraged continued reporting of adverse events with enfortumab vedotin to the FDA via the MedWatch portal.
The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CMS’s proposed 22% cut to radiation oncology is ‘tone deaf’
The changes, proposed by the Centers for Medicare & Medicaid Services to their Radiation Oncology (RO) Model, have been challenged primarily by the American Society for Radiation Oncology (ASTRO), but by other groups as well.
These excessive reductions will jeopardize access to lifesaving radiation therapy services for Medicare beneficiaries at a time when the U.S. health care system needs “all doors open” to treat patients with cancer, says ASTRO.
The proposed cuts are scheduled to take effect Jan. 1 and will be mandatory for the 30% of providers that will be randomly selected to participate.
The timing could not be worse, says the Community Oncology Alliance. “How can payment be ratcheted down on a vital aspect of cancer in the middle of a pandemic?” said Ted Okon, MBA, executive director of COA. “What was CMS thinking? These are extreme circumstances, and this is so ill-timed and so tone deaf that it just takes my breath away.”
He pointed out that with hospitals being overrun with COVID-19 patients, community practices have to keep their doors open to treat patients. “This is an extended public health emergency, and a variant can reignite the surge,” said Mr. Okon. “CMS should be asking practices what they can do to help them – and not trying to make drastic cuts.”
Mr. Okon is also concerned that as a result of the pandemic, “we are going to be seeing more advanced cancers, which are more difficult and expensive to treat, and radiation therapy is going to come into play,” he said. “These are serious and unintended consequences, and CMS needs to come out of their [Washington] D.C. bubble and see what’s really going on.”
The timing of the rollout is particularly precarious, given the financial upheaval caused by the COVID-19 pandemic, agrees Constantine Mantz, MD, ASTRO’s Health Policy Council vice-chair.
“Medicare’s proposed cuts, unfortunately, compound the enormous financial challenges imposed by the COVID-19 pandemic on physicians and their practices,” said Dr. Mantz. “Radiation oncology is particularly at risk given its dependence on expensive treatment equipment to deliver cancer care.”
The high costs of maintaining this equipment remain the same whether the equipment is used or not. “This means that fewer patients being seen during the pandemic combined with these steep reimbursement cuts in the near future risk the continued viability of many centers and their ability to provide lifesaving cancer treatment,” he said.
ASTRO calls on Congress to intervene
ASTRO has asked President Biden and Congress to intervene immediately on not only the Radiation Oncology model but the severe cuts that were proposed for the 2022 Medicare Physician Fee Schedule.
“The RO Model, which was last updated in the 2022 Medicare Hospital Outpatient Prospective Payment System Proposed Rule, would cut payments for radiation therapy services by 3.75% for physicians and 4.75% for facilities,” said Dr. Mantz. “This cut would be in addition to an 8.75% cut to radiation oncology in the 2022 Medicare Physician Fee Schedule Proposed Rule.”
As a result, the physicians and facilities that are required to participate in the RO Model are facing steep declines in Medicare reimbursement. “This amounts to well over 10% for their patients covered by Medicare next year,” Dr. Mantz told this news organization.
The radiation oncology model
The goal of the RO Model is to test a change in the way radiation therapy services are paid – from the current “fee-for-service” payments” to prospective, site-neutral, modality-agnostic, episode-based payments that incentivize physicians to deliver higher-value care. It requires mandatory participation of practices.
The Center for Medicare and Medicaid Innovation published a final rule in September 2020 that established the RO Model, which was to begin on Jan. 1, 2021. However, because of the ongoing COVID-19 pandemic, the start of the RO Model was delayed until July 1, 2021, and subsequently, the Consolidated Appropriations Act, 2021, included a provision that prohibits implementation of the RO Model before Jan. 1, 2022.
Further changes to the RO model were proposed last month, which included some slight revisions to the discount factor. But ASTRO points out that these revisions did not address numerous concerns raised by both the radiation oncology community and a broad coalition of medical provider groups, patients, hospitals, health systems, and bipartisan members of Congress.
The new model would provide an alternative to the traditional fee-for-service payments. Instead, the payments are prospective and episode-based, and based on the cancer diagnosis. It would cover radiation therapy that is administered during a 90-day episode, and would meet the included cancer type criteria described in the final rule.
The RO model would use “site-neutral payment” by establishing a common, adjusted national base payment amount for the episode, regardless of the setting where it is administered.
The episode payments would be divided into professional and technical components to allow the current claims systems for the Physician Fee Schedule (PFS) and the Outpatient Prospective Payment System (OPPS) to be used to adjudicate claims as well as to maintain consistency with existing business relationships.
Another aspect is that the model links “payment” to “quality” using reporting and performance on quality measures, clinical data reporting, and patient experience as factors when determining payment to RO participants. Finally, providers will be randomly selected and participation is mandatory.
Mr. Okon feels that the idea of a mandatory model is wrong. “They are going to be taking 30% of practices to participate in an experiment,” he said. “Mandatory means that you can’t get enough people to participate so it is mandated to force them into it.”
Dr. Mantz also noted that the model is going to have a widespread impact on a wide range of issues. “Sharply reduced reimbursement for radiation therapy services under the RO Model is expected to delay, if not prevent, the equipment upgrades and other improvements that are necessary for practices to continue to provide high-quality, high-value cancer care.
“These problematic barriers to access advanced treatment technology also come at a critical time for radiation oncology, in that we already are seeing more difficult-to-treat cancers and caring for patients with more advanced-stage diseases due to delayed diagnoses during the peak of the pandemic last year.”
In addition, the RO model, in its current inception, is expected to further widen existing gaps in access to cancer care, disproportionately harming patients from marginalized groups, such as poor patients and medically underserved patients.
“For example, ASTRO analyses have demonstrated that patients in rural areas currently face significantly reduced access to stereotactic radiotherapy and lifesaving brachytherapy treatments, compared to patients in urban areas,” said Dr. Mantz. “It’s difficult to imagine that these serious health inequities could even begin to be addressed with the aggregate payment cuts imposed by the RO model.”
A version of this article first appeared on Medscape.com.
The changes, proposed by the Centers for Medicare & Medicaid Services to their Radiation Oncology (RO) Model, have been challenged primarily by the American Society for Radiation Oncology (ASTRO), but by other groups as well.
These excessive reductions will jeopardize access to lifesaving radiation therapy services for Medicare beneficiaries at a time when the U.S. health care system needs “all doors open” to treat patients with cancer, says ASTRO.
The proposed cuts are scheduled to take effect Jan. 1 and will be mandatory for the 30% of providers that will be randomly selected to participate.
The timing could not be worse, says the Community Oncology Alliance. “How can payment be ratcheted down on a vital aspect of cancer in the middle of a pandemic?” said Ted Okon, MBA, executive director of COA. “What was CMS thinking? These are extreme circumstances, and this is so ill-timed and so tone deaf that it just takes my breath away.”
He pointed out that with hospitals being overrun with COVID-19 patients, community practices have to keep their doors open to treat patients. “This is an extended public health emergency, and a variant can reignite the surge,” said Mr. Okon. “CMS should be asking practices what they can do to help them – and not trying to make drastic cuts.”
Mr. Okon is also concerned that as a result of the pandemic, “we are going to be seeing more advanced cancers, which are more difficult and expensive to treat, and radiation therapy is going to come into play,” he said. “These are serious and unintended consequences, and CMS needs to come out of their [Washington] D.C. bubble and see what’s really going on.”
The timing of the rollout is particularly precarious, given the financial upheaval caused by the COVID-19 pandemic, agrees Constantine Mantz, MD, ASTRO’s Health Policy Council vice-chair.
“Medicare’s proposed cuts, unfortunately, compound the enormous financial challenges imposed by the COVID-19 pandemic on physicians and their practices,” said Dr. Mantz. “Radiation oncology is particularly at risk given its dependence on expensive treatment equipment to deliver cancer care.”
The high costs of maintaining this equipment remain the same whether the equipment is used or not. “This means that fewer patients being seen during the pandemic combined with these steep reimbursement cuts in the near future risk the continued viability of many centers and their ability to provide lifesaving cancer treatment,” he said.
ASTRO calls on Congress to intervene
ASTRO has asked President Biden and Congress to intervene immediately on not only the Radiation Oncology model but the severe cuts that were proposed for the 2022 Medicare Physician Fee Schedule.
“The RO Model, which was last updated in the 2022 Medicare Hospital Outpatient Prospective Payment System Proposed Rule, would cut payments for radiation therapy services by 3.75% for physicians and 4.75% for facilities,” said Dr. Mantz. “This cut would be in addition to an 8.75% cut to radiation oncology in the 2022 Medicare Physician Fee Schedule Proposed Rule.”
As a result, the physicians and facilities that are required to participate in the RO Model are facing steep declines in Medicare reimbursement. “This amounts to well over 10% for their patients covered by Medicare next year,” Dr. Mantz told this news organization.
The radiation oncology model
The goal of the RO Model is to test a change in the way radiation therapy services are paid – from the current “fee-for-service” payments” to prospective, site-neutral, modality-agnostic, episode-based payments that incentivize physicians to deliver higher-value care. It requires mandatory participation of practices.
The Center for Medicare and Medicaid Innovation published a final rule in September 2020 that established the RO Model, which was to begin on Jan. 1, 2021. However, because of the ongoing COVID-19 pandemic, the start of the RO Model was delayed until July 1, 2021, and subsequently, the Consolidated Appropriations Act, 2021, included a provision that prohibits implementation of the RO Model before Jan. 1, 2022.
Further changes to the RO model were proposed last month, which included some slight revisions to the discount factor. But ASTRO points out that these revisions did not address numerous concerns raised by both the radiation oncology community and a broad coalition of medical provider groups, patients, hospitals, health systems, and bipartisan members of Congress.
The new model would provide an alternative to the traditional fee-for-service payments. Instead, the payments are prospective and episode-based, and based on the cancer diagnosis. It would cover radiation therapy that is administered during a 90-day episode, and would meet the included cancer type criteria described in the final rule.
The RO model would use “site-neutral payment” by establishing a common, adjusted national base payment amount for the episode, regardless of the setting where it is administered.
The episode payments would be divided into professional and technical components to allow the current claims systems for the Physician Fee Schedule (PFS) and the Outpatient Prospective Payment System (OPPS) to be used to adjudicate claims as well as to maintain consistency with existing business relationships.
Another aspect is that the model links “payment” to “quality” using reporting and performance on quality measures, clinical data reporting, and patient experience as factors when determining payment to RO participants. Finally, providers will be randomly selected and participation is mandatory.
Mr. Okon feels that the idea of a mandatory model is wrong. “They are going to be taking 30% of practices to participate in an experiment,” he said. “Mandatory means that you can’t get enough people to participate so it is mandated to force them into it.”
Dr. Mantz also noted that the model is going to have a widespread impact on a wide range of issues. “Sharply reduced reimbursement for radiation therapy services under the RO Model is expected to delay, if not prevent, the equipment upgrades and other improvements that are necessary for practices to continue to provide high-quality, high-value cancer care.
“These problematic barriers to access advanced treatment technology also come at a critical time for radiation oncology, in that we already are seeing more difficult-to-treat cancers and caring for patients with more advanced-stage diseases due to delayed diagnoses during the peak of the pandemic last year.”
In addition, the RO model, in its current inception, is expected to further widen existing gaps in access to cancer care, disproportionately harming patients from marginalized groups, such as poor patients and medically underserved patients.
“For example, ASTRO analyses have demonstrated that patients in rural areas currently face significantly reduced access to stereotactic radiotherapy and lifesaving brachytherapy treatments, compared to patients in urban areas,” said Dr. Mantz. “It’s difficult to imagine that these serious health inequities could even begin to be addressed with the aggregate payment cuts imposed by the RO model.”
A version of this article first appeared on Medscape.com.
The changes, proposed by the Centers for Medicare & Medicaid Services to their Radiation Oncology (RO) Model, have been challenged primarily by the American Society for Radiation Oncology (ASTRO), but by other groups as well.
These excessive reductions will jeopardize access to lifesaving radiation therapy services for Medicare beneficiaries at a time when the U.S. health care system needs “all doors open” to treat patients with cancer, says ASTRO.
The proposed cuts are scheduled to take effect Jan. 1 and will be mandatory for the 30% of providers that will be randomly selected to participate.
The timing could not be worse, says the Community Oncology Alliance. “How can payment be ratcheted down on a vital aspect of cancer in the middle of a pandemic?” said Ted Okon, MBA, executive director of COA. “What was CMS thinking? These are extreme circumstances, and this is so ill-timed and so tone deaf that it just takes my breath away.”
He pointed out that with hospitals being overrun with COVID-19 patients, community practices have to keep their doors open to treat patients. “This is an extended public health emergency, and a variant can reignite the surge,” said Mr. Okon. “CMS should be asking practices what they can do to help them – and not trying to make drastic cuts.”
Mr. Okon is also concerned that as a result of the pandemic, “we are going to be seeing more advanced cancers, which are more difficult and expensive to treat, and radiation therapy is going to come into play,” he said. “These are serious and unintended consequences, and CMS needs to come out of their [Washington] D.C. bubble and see what’s really going on.”
The timing of the rollout is particularly precarious, given the financial upheaval caused by the COVID-19 pandemic, agrees Constantine Mantz, MD, ASTRO’s Health Policy Council vice-chair.
“Medicare’s proposed cuts, unfortunately, compound the enormous financial challenges imposed by the COVID-19 pandemic on physicians and their practices,” said Dr. Mantz. “Radiation oncology is particularly at risk given its dependence on expensive treatment equipment to deliver cancer care.”
The high costs of maintaining this equipment remain the same whether the equipment is used or not. “This means that fewer patients being seen during the pandemic combined with these steep reimbursement cuts in the near future risk the continued viability of many centers and their ability to provide lifesaving cancer treatment,” he said.
ASTRO calls on Congress to intervene
ASTRO has asked President Biden and Congress to intervene immediately on not only the Radiation Oncology model but the severe cuts that were proposed for the 2022 Medicare Physician Fee Schedule.
“The RO Model, which was last updated in the 2022 Medicare Hospital Outpatient Prospective Payment System Proposed Rule, would cut payments for radiation therapy services by 3.75% for physicians and 4.75% for facilities,” said Dr. Mantz. “This cut would be in addition to an 8.75% cut to radiation oncology in the 2022 Medicare Physician Fee Schedule Proposed Rule.”
As a result, the physicians and facilities that are required to participate in the RO Model are facing steep declines in Medicare reimbursement. “This amounts to well over 10% for their patients covered by Medicare next year,” Dr. Mantz told this news organization.
The radiation oncology model
The goal of the RO Model is to test a change in the way radiation therapy services are paid – from the current “fee-for-service” payments” to prospective, site-neutral, modality-agnostic, episode-based payments that incentivize physicians to deliver higher-value care. It requires mandatory participation of practices.
The Center for Medicare and Medicaid Innovation published a final rule in September 2020 that established the RO Model, which was to begin on Jan. 1, 2021. However, because of the ongoing COVID-19 pandemic, the start of the RO Model was delayed until July 1, 2021, and subsequently, the Consolidated Appropriations Act, 2021, included a provision that prohibits implementation of the RO Model before Jan. 1, 2022.
Further changes to the RO model were proposed last month, which included some slight revisions to the discount factor. But ASTRO points out that these revisions did not address numerous concerns raised by both the radiation oncology community and a broad coalition of medical provider groups, patients, hospitals, health systems, and bipartisan members of Congress.
The new model would provide an alternative to the traditional fee-for-service payments. Instead, the payments are prospective and episode-based, and based on the cancer diagnosis. It would cover radiation therapy that is administered during a 90-day episode, and would meet the included cancer type criteria described in the final rule.
The RO model would use “site-neutral payment” by establishing a common, adjusted national base payment amount for the episode, regardless of the setting where it is administered.
The episode payments would be divided into professional and technical components to allow the current claims systems for the Physician Fee Schedule (PFS) and the Outpatient Prospective Payment System (OPPS) to be used to adjudicate claims as well as to maintain consistency with existing business relationships.
Another aspect is that the model links “payment” to “quality” using reporting and performance on quality measures, clinical data reporting, and patient experience as factors when determining payment to RO participants. Finally, providers will be randomly selected and participation is mandatory.
Mr. Okon feels that the idea of a mandatory model is wrong. “They are going to be taking 30% of practices to participate in an experiment,” he said. “Mandatory means that you can’t get enough people to participate so it is mandated to force them into it.”
Dr. Mantz also noted that the model is going to have a widespread impact on a wide range of issues. “Sharply reduced reimbursement for radiation therapy services under the RO Model is expected to delay, if not prevent, the equipment upgrades and other improvements that are necessary for practices to continue to provide high-quality, high-value cancer care.
“These problematic barriers to access advanced treatment technology also come at a critical time for radiation oncology, in that we already are seeing more difficult-to-treat cancers and caring for patients with more advanced-stage diseases due to delayed diagnoses during the peak of the pandemic last year.”
In addition, the RO model, in its current inception, is expected to further widen existing gaps in access to cancer care, disproportionately harming patients from marginalized groups, such as poor patients and medically underserved patients.
“For example, ASTRO analyses have demonstrated that patients in rural areas currently face significantly reduced access to stereotactic radiotherapy and lifesaving brachytherapy treatments, compared to patients in urban areas,” said Dr. Mantz. “It’s difficult to imagine that these serious health inequities could even begin to be addressed with the aggregate payment cuts imposed by the RO model.”
A version of this article first appeared on Medscape.com.