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Soon-to-be medical student awarded $10K after spotting melanoma
A soon-to-be medical student and former oncology ward volunteer has received a $10,000 scholarship for her education recently after tipping off a Vancouver Canucks staff member about a cancerous mole on the back of his neck during a National Hockey League game in Seattle this past October.
Sitting immediately behind the visiting team’s bench, Nadia Popovici wrote a large-font message on her cell phone and tapped the protective glass to get the attention of Brian Hamilton, assistant equipment manager for the Canucks.
“The mole on the back of your neck is possibly cancerous. Please go see a doctor!” read the message.
Mr. Hamilton acted on the tip and was eventually diagnosed with a malignant stage II melanoma, according to a report in the Seattle Times.
As noted in a Medscape Q&A, “ABCDE” is the acronym that indicates the visible, physical characteristics suggestive of melanoma. ABCDE stands for asymmetry, irregular border, color variations (especially red, white, and blue tones in a brown or black lesion), diameter greater than 6 mm, and elevated surface. The lesions may itch, bleed, ulcerate, or develop satellites.
The Canucks returned to Seattle recently for another game against the Seattle Kraken, and the visiting team posted a note on social media from Mr. Hamilton seeking the identity of the good Samaritan.
“... the message you showed me on your cell phone will forever be etched into my brain and has made a true life-changing difference for me and my family,” wrote Mr. Hamilton.
Within hours, Ms. Popovici’s mother, whose family has season tickets to the Seattle team’s games, responded to the message.
Ms. Popovici and Mr. Hamilton met up again at the Jan. 1 game, where Ms. Popovici was rewarded with a $10,000 medical school scholarship in a surprise announcement, shared on Twitter and liked more than 42,000 times.
“She didn’t take me out of a burning car like the big stories, but she took me out of a slow fire. And the words out of the doctor’s mouth were, if I ignored that for 4-5 years, I wouldn’t be here,” Mr. Hamilton said at a news conference on Jan. 1.
Ms. Popovici says she has been accepted to several medical schools and will start school in the fall, according to a press release from the National Hockey League.
More money for medical school may be on the way for Ms. Popovici after a GoFundMe page was started. With a goal of $25,000, the fund had received just over $2,500 as of Jan. 4.
“The teams made a kind gesture of giving her 10K, but I think we can do better!” Josh Doxey, a sales manager from Lehi, Utah, wrote on the page he created for Ms. Popovici.
Mr. Doxey told this news organization, “I started the GoFundMe thinking it would be a nice gesture especially for someone going into health care after 2 crazy years of COVID ... I have gotten in touch with her and her mother, and have been chatting with both. They both seem incredibly kind, grateful, and humble.”
A version of this article first appeared on Medscape.com.
A soon-to-be medical student and former oncology ward volunteer has received a $10,000 scholarship for her education recently after tipping off a Vancouver Canucks staff member about a cancerous mole on the back of his neck during a National Hockey League game in Seattle this past October.
Sitting immediately behind the visiting team’s bench, Nadia Popovici wrote a large-font message on her cell phone and tapped the protective glass to get the attention of Brian Hamilton, assistant equipment manager for the Canucks.
“The mole on the back of your neck is possibly cancerous. Please go see a doctor!” read the message.
Mr. Hamilton acted on the tip and was eventually diagnosed with a malignant stage II melanoma, according to a report in the Seattle Times.
As noted in a Medscape Q&A, “ABCDE” is the acronym that indicates the visible, physical characteristics suggestive of melanoma. ABCDE stands for asymmetry, irregular border, color variations (especially red, white, and blue tones in a brown or black lesion), diameter greater than 6 mm, and elevated surface. The lesions may itch, bleed, ulcerate, or develop satellites.
The Canucks returned to Seattle recently for another game against the Seattle Kraken, and the visiting team posted a note on social media from Mr. Hamilton seeking the identity of the good Samaritan.
“... the message you showed me on your cell phone will forever be etched into my brain and has made a true life-changing difference for me and my family,” wrote Mr. Hamilton.
Within hours, Ms. Popovici’s mother, whose family has season tickets to the Seattle team’s games, responded to the message.
Ms. Popovici and Mr. Hamilton met up again at the Jan. 1 game, where Ms. Popovici was rewarded with a $10,000 medical school scholarship in a surprise announcement, shared on Twitter and liked more than 42,000 times.
“She didn’t take me out of a burning car like the big stories, but she took me out of a slow fire. And the words out of the doctor’s mouth were, if I ignored that for 4-5 years, I wouldn’t be here,” Mr. Hamilton said at a news conference on Jan. 1.
Ms. Popovici says she has been accepted to several medical schools and will start school in the fall, according to a press release from the National Hockey League.
More money for medical school may be on the way for Ms. Popovici after a GoFundMe page was started. With a goal of $25,000, the fund had received just over $2,500 as of Jan. 4.
“The teams made a kind gesture of giving her 10K, but I think we can do better!” Josh Doxey, a sales manager from Lehi, Utah, wrote on the page he created for Ms. Popovici.
Mr. Doxey told this news organization, “I started the GoFundMe thinking it would be a nice gesture especially for someone going into health care after 2 crazy years of COVID ... I have gotten in touch with her and her mother, and have been chatting with both. They both seem incredibly kind, grateful, and humble.”
A version of this article first appeared on Medscape.com.
A soon-to-be medical student and former oncology ward volunteer has received a $10,000 scholarship for her education recently after tipping off a Vancouver Canucks staff member about a cancerous mole on the back of his neck during a National Hockey League game in Seattle this past October.
Sitting immediately behind the visiting team’s bench, Nadia Popovici wrote a large-font message on her cell phone and tapped the protective glass to get the attention of Brian Hamilton, assistant equipment manager for the Canucks.
“The mole on the back of your neck is possibly cancerous. Please go see a doctor!” read the message.
Mr. Hamilton acted on the tip and was eventually diagnosed with a malignant stage II melanoma, according to a report in the Seattle Times.
As noted in a Medscape Q&A, “ABCDE” is the acronym that indicates the visible, physical characteristics suggestive of melanoma. ABCDE stands for asymmetry, irregular border, color variations (especially red, white, and blue tones in a brown or black lesion), diameter greater than 6 mm, and elevated surface. The lesions may itch, bleed, ulcerate, or develop satellites.
The Canucks returned to Seattle recently for another game against the Seattle Kraken, and the visiting team posted a note on social media from Mr. Hamilton seeking the identity of the good Samaritan.
“... the message you showed me on your cell phone will forever be etched into my brain and has made a true life-changing difference for me and my family,” wrote Mr. Hamilton.
Within hours, Ms. Popovici’s mother, whose family has season tickets to the Seattle team’s games, responded to the message.
Ms. Popovici and Mr. Hamilton met up again at the Jan. 1 game, where Ms. Popovici was rewarded with a $10,000 medical school scholarship in a surprise announcement, shared on Twitter and liked more than 42,000 times.
“She didn’t take me out of a burning car like the big stories, but she took me out of a slow fire. And the words out of the doctor’s mouth were, if I ignored that for 4-5 years, I wouldn’t be here,” Mr. Hamilton said at a news conference on Jan. 1.
Ms. Popovici says she has been accepted to several medical schools and will start school in the fall, according to a press release from the National Hockey League.
More money for medical school may be on the way for Ms. Popovici after a GoFundMe page was started. With a goal of $25,000, the fund had received just over $2,500 as of Jan. 4.
“The teams made a kind gesture of giving her 10K, but I think we can do better!” Josh Doxey, a sales manager from Lehi, Utah, wrote on the page he created for Ms. Popovici.
Mr. Doxey told this news organization, “I started the GoFundMe thinking it would be a nice gesture especially for someone going into health care after 2 crazy years of COVID ... I have gotten in touch with her and her mother, and have been chatting with both. They both seem incredibly kind, grateful, and humble.”
A version of this article first appeared on Medscape.com.
FDA approves time-saving combo for r/r multiple myeloma
The U.S. Food and Drug Administration who have had one to three prior lines of therapy.
Using the newly approved combination in this setting is a time-saver for patients and clinics, observed an investigator.
“The approval of subcutaneous daratumumab in combination with Kd will help clinicians address unmet patient needs by reducing the administration time from hours to just minutes and reducing the frequency of infusion-related reactions, as compared to the intravenous daratumumab formulation in combination with Kd,” said Ajai Chari, MD, of Mount Sinai Cancer Clinical Trials Office in New York City in a Janssen press statement.
Efficacy data for the new approval come from a single-arm cohort of PLEIADES, a multicohort, open-label trial. The cohort included 66 patients with relapsed or refractory multiple myeloma who had received one or more prior lines of therapy. Patients received daratumumab + hyaluronidase-fihj subcutaneously in combination with carfilzomib and dexamethasone.
The main efficacy outcome measure was overall response rate, which was 84.8%. At a median follow-up of 9.2 months, the median duration of response had not been reached.
The response rate with the new combination, which features a subcutaneous injection, was akin to those with the older combination, which features the more time-consuming IV administration and was FDA approved, according to the company press release.
The most common adverse reactions (≥20%) occurring in patients treated with Darzalex Faspro, Kyprolis, and dexamethasone were upper respiratory tract infections, fatigue, insomnia, hypertension, diarrhea, cough, dyspnea, headache, pyrexia, nausea, and edema peripheral.
A version of this article first appeared on Medscape.com .
The U.S. Food and Drug Administration who have had one to three prior lines of therapy.
Using the newly approved combination in this setting is a time-saver for patients and clinics, observed an investigator.
“The approval of subcutaneous daratumumab in combination with Kd will help clinicians address unmet patient needs by reducing the administration time from hours to just minutes and reducing the frequency of infusion-related reactions, as compared to the intravenous daratumumab formulation in combination with Kd,” said Ajai Chari, MD, of Mount Sinai Cancer Clinical Trials Office in New York City in a Janssen press statement.
Efficacy data for the new approval come from a single-arm cohort of PLEIADES, a multicohort, open-label trial. The cohort included 66 patients with relapsed or refractory multiple myeloma who had received one or more prior lines of therapy. Patients received daratumumab + hyaluronidase-fihj subcutaneously in combination with carfilzomib and dexamethasone.
The main efficacy outcome measure was overall response rate, which was 84.8%. At a median follow-up of 9.2 months, the median duration of response had not been reached.
The response rate with the new combination, which features a subcutaneous injection, was akin to those with the older combination, which features the more time-consuming IV administration and was FDA approved, according to the company press release.
The most common adverse reactions (≥20%) occurring in patients treated with Darzalex Faspro, Kyprolis, and dexamethasone were upper respiratory tract infections, fatigue, insomnia, hypertension, diarrhea, cough, dyspnea, headache, pyrexia, nausea, and edema peripheral.
A version of this article first appeared on Medscape.com .
The U.S. Food and Drug Administration who have had one to three prior lines of therapy.
Using the newly approved combination in this setting is a time-saver for patients and clinics, observed an investigator.
“The approval of subcutaneous daratumumab in combination with Kd will help clinicians address unmet patient needs by reducing the administration time from hours to just minutes and reducing the frequency of infusion-related reactions, as compared to the intravenous daratumumab formulation in combination with Kd,” said Ajai Chari, MD, of Mount Sinai Cancer Clinical Trials Office in New York City in a Janssen press statement.
Efficacy data for the new approval come from a single-arm cohort of PLEIADES, a multicohort, open-label trial. The cohort included 66 patients with relapsed or refractory multiple myeloma who had received one or more prior lines of therapy. Patients received daratumumab + hyaluronidase-fihj subcutaneously in combination with carfilzomib and dexamethasone.
The main efficacy outcome measure was overall response rate, which was 84.8%. At a median follow-up of 9.2 months, the median duration of response had not been reached.
The response rate with the new combination, which features a subcutaneous injection, was akin to those with the older combination, which features the more time-consuming IV administration and was FDA approved, according to the company press release.
The most common adverse reactions (≥20%) occurring in patients treated with Darzalex Faspro, Kyprolis, and dexamethasone were upper respiratory tract infections, fatigue, insomnia, hypertension, diarrhea, cough, dyspnea, headache, pyrexia, nausea, and edema peripheral.
A version of this article first appeared on Medscape.com .
What’s hot at the world’s premiere breast cancer meeting
Dr. Arteaga, the meeting’s codirector, said the first-ever hybrid symposium will take place virtually from Dec. 7 to 10 as well as in person. Online availability appears to be a boon to attendance, with a record 9,325 registrants for the 2020 symposium, held only virtually because of the COVID-19 pandemic.
The meeting will have an app available, which can be accessed by searching “San Antonio Breast Cancer Symposium” (Google Play for Android, Apple for iOS) and downloading, or by going to www.core-apps.com/dl/sabcs from a desktop computer.
Dr. Arteaga provided a sneak peek of the most exciting research being presented at the upcoming meeting.
On the horizon for advanced breast cancer
A “very important” study of an investigational oral agent employed in heavily pretreated postmenopausal women with estrogen receptor–positive (ER+) advanced breast cancer headlines the meeting.
This international, multicenter trial could have “practice-changing implications,” Dr. Arteaga said in an interview.
The phase 3 EMERALD trial (abstract GS2-02) pits elacestrant, a selective estrogen receptor degrader (SERD), against standard endocrine therapy (fulvestrant or an aromatase inhibitor) in patients with metastatic breast cancer whose disease has progressed after treatment with at least one endocrine therapy and a CDK4/6 inhibitor.
The trial is important because many patients with breast cancer have estrogen receptor mutations, which are a “major mechanism of [drug] resistance” and thus progression on earlier therapy, Dr. Arteaga said.
Elacestrant is in good company among a plethora of oral SERDs under investigation in advanced breast cancer; however, currently, fulvestrant – which requires an intramuscular injection in the buttocks every month – is the only approved SERD.
“There’s plenty of preclinical data that suggest that these drugs [SERDs] may have activity against these mutant forms of the receptor, which occur in up to 40% of patients with advanced ER+ breast cancer,” he explained.
Researchers will present data on two primary outcome measures from the phase 3 trial: progression-free survival (PFS) based on mutations of the estrogen receptor 1 gene (ESR1-mut) and PFS in all subjects regardless of ESR1 status.
In addition to the EMERALD trial, PADA-1 (abstract GS3-05) is another important randomized, phase 3 trial focused on treating estrogen receptor mutations in patients with metastatic disease, said Dr. Arteaga.
The trial has enrolled patients with ER+ metastatic breast cancer who received an aromatase inhibitor (letrozole, anastrozole, or exemestane) and the CDK4/6 inhibitor palbociclib as first-line therapy.
In step 1 of the trial, approximately 1,000 patients were screened for circulating blood ESR1 mutation detection at regular intervals while being treated with palbociclib and an aromatase inhibitor in a continuous scheme until tumor progression or ESR1 mutation detection.
In step 2, up to 200 patients with a rising circulating ESR1 mutation and no tumor progression were randomized 1:1 to no change in therapy until tumor progression or to receive palbociclib plus fulvestrant until tumor progression.
The trial examines the safety and efficacy of “a clinical conundrum that we face” in this setting: whether or not to switch treatment from an aromatase inhibitor to fulvestrant while continuing a CDK4/6 inhibitor at the sign of mutation detection, Dr. Arteaga explained.
Refining who gets the ‘kitchen sink’
Dr. Arteaga highlighted two trials focused on the immune checkpoint inhibitor pembrolizumab.
The phase 3 KEYNOTE-522 study led to the approval of neoadjuvant pembrolizumab plus chemotherapy for early-stage triple-negative breast cancer (TNBC) in July 2021. At this year’s SABCS, researchers will present new data from KEYNOTE-522 (abstract GS1-01), representing final results from the trial’s event-free survival (EFS) outcome.
Previously, investigators reported a statistically significant and clinically meaningful improvement in EFS. These data suggest “that deploying immunotherapy early before surgery ... may be curative in some patients,” Dr. Arteaga said. The new data will allow the “robustness and consistency” of the earlier findings to be assessed.
But, he added, this is a “tough” treatment, which includes five drugs. “It’s the kitchen sink, and not everybody needs the kitchen sink. It’s important to refine these findings. Some patients may not need pembrolizumab, but some do.”
The second trial exploring pembrolizumab – KEYNOTE-355 (abstract GS1-02) – mirrors KEYNOTE-522 but in patients with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1.
Previously, investigators reported that pembrolizumab combined with chemotherapy showed statistically significant improvements in overall survival and PFS compared to placebo plus chemotherapy. At the 2021 SABCS, researchers will provide final study results, including outcomes in subgroups of patients by additional combined positive score cutoffs.
Metformin trial: ‘This is it’
Dr. Arteaga highlighted CCTGMA.32 (abstract GS1-08), a phase 3 randomized, placebo-controlled adjuvant trial of the diabetes drug metformin versus placebo in early breast cancer. Results of the primary efficacy analysis of the trial will be presented at the meeting.
The Canadian-led study seeks to determine if metformin can decrease breast cancer cell growth and work with cancer therapies to prevent disease recurrence. The study design calls for patients to take twice-daily oral metformin or placebo pills for up to 5 years in the absence of disease progression.
The primary outcome of the 3,500-plus patient trial is invasive disease-free survival in hormone receptor (ER and PgR) negative and positive (ER and/or PgR) subgroups.
“Metformin has actually been associated with improved survival [in breast cancer] in patients on chemotherapy. But we don’t know exactly how,” he said. “There’s never been a head-to-head comparison in the adjuvant setting [before]. This is it.”
TKI for breast cancer with brain mets
The SABCS codirector spotlighted an updated overall survival analysis of the randomized phase 3 PHOEBE trial (abstract GS3-02).
Previous research confirmed the superiority of pyrotinib, a novel TKI targeting HER1, HER2, and HER4, over lapatinib when given in combination with capecitabine in HER2-positive metastatic breast cancer.
In the United States, the lapatinib-capecitabine combination is “mostly used” in patients with HER2 metastatic disease and brain metastases who also undergo stereotactic radiation, Dr. Arteaga said.
This use has continued despite groundbreaking results from the HER2CLIMB trial, featuring the TKI tucatinib, he said.
As reported last year, adding tucatinib to trastuzumab and capecitabine in patients with HER2-positive breast cancer and brain metastases increased median overall survival from 12 months to 18.1 months. The results were called the first of their kind at that time.
The pyrotinib study may matter to American clinicians because pyrotinib is used mostly in China, not the United States, and this analysis suggests that pyrotinib could be part of the armamentarium in the United States, alongside tucatinib.
TKIs are like Coke and Pepsi, Dr. Arteaga said: “Similar but not identical.” Therefore, it is worth taking a look at the new study, he said. “There may be some benefit in having more than one [TKI] in the therapeutic armamentarium.”
Dr. Arteaga receives or has received grant support from Pfizer and Lilly and serves or has served in a scientific advisory role with Novartis, Lilly, TAIHO Oncology, Daiichi Sankyo, Merck, AstraZeneca, OrigiMed, Immunomedics, ARVINAS, Sanofi, Athenex, and the Susan G. Komen Foundation. He also holds minor stock options from Provista.
A version of this article first appeared on Medscape.com.
Dr. Arteaga, the meeting’s codirector, said the first-ever hybrid symposium will take place virtually from Dec. 7 to 10 as well as in person. Online availability appears to be a boon to attendance, with a record 9,325 registrants for the 2020 symposium, held only virtually because of the COVID-19 pandemic.
The meeting will have an app available, which can be accessed by searching “San Antonio Breast Cancer Symposium” (Google Play for Android, Apple for iOS) and downloading, or by going to www.core-apps.com/dl/sabcs from a desktop computer.
Dr. Arteaga provided a sneak peek of the most exciting research being presented at the upcoming meeting.
On the horizon for advanced breast cancer
A “very important” study of an investigational oral agent employed in heavily pretreated postmenopausal women with estrogen receptor–positive (ER+) advanced breast cancer headlines the meeting.
This international, multicenter trial could have “practice-changing implications,” Dr. Arteaga said in an interview.
The phase 3 EMERALD trial (abstract GS2-02) pits elacestrant, a selective estrogen receptor degrader (SERD), against standard endocrine therapy (fulvestrant or an aromatase inhibitor) in patients with metastatic breast cancer whose disease has progressed after treatment with at least one endocrine therapy and a CDK4/6 inhibitor.
The trial is important because many patients with breast cancer have estrogen receptor mutations, which are a “major mechanism of [drug] resistance” and thus progression on earlier therapy, Dr. Arteaga said.
Elacestrant is in good company among a plethora of oral SERDs under investigation in advanced breast cancer; however, currently, fulvestrant – which requires an intramuscular injection in the buttocks every month – is the only approved SERD.
“There’s plenty of preclinical data that suggest that these drugs [SERDs] may have activity against these mutant forms of the receptor, which occur in up to 40% of patients with advanced ER+ breast cancer,” he explained.
Researchers will present data on two primary outcome measures from the phase 3 trial: progression-free survival (PFS) based on mutations of the estrogen receptor 1 gene (ESR1-mut) and PFS in all subjects regardless of ESR1 status.
In addition to the EMERALD trial, PADA-1 (abstract GS3-05) is another important randomized, phase 3 trial focused on treating estrogen receptor mutations in patients with metastatic disease, said Dr. Arteaga.
The trial has enrolled patients with ER+ metastatic breast cancer who received an aromatase inhibitor (letrozole, anastrozole, or exemestane) and the CDK4/6 inhibitor palbociclib as first-line therapy.
In step 1 of the trial, approximately 1,000 patients were screened for circulating blood ESR1 mutation detection at regular intervals while being treated with palbociclib and an aromatase inhibitor in a continuous scheme until tumor progression or ESR1 mutation detection.
In step 2, up to 200 patients with a rising circulating ESR1 mutation and no tumor progression were randomized 1:1 to no change in therapy until tumor progression or to receive palbociclib plus fulvestrant until tumor progression.
The trial examines the safety and efficacy of “a clinical conundrum that we face” in this setting: whether or not to switch treatment from an aromatase inhibitor to fulvestrant while continuing a CDK4/6 inhibitor at the sign of mutation detection, Dr. Arteaga explained.
Refining who gets the ‘kitchen sink’
Dr. Arteaga highlighted two trials focused on the immune checkpoint inhibitor pembrolizumab.
The phase 3 KEYNOTE-522 study led to the approval of neoadjuvant pembrolizumab plus chemotherapy for early-stage triple-negative breast cancer (TNBC) in July 2021. At this year’s SABCS, researchers will present new data from KEYNOTE-522 (abstract GS1-01), representing final results from the trial’s event-free survival (EFS) outcome.
Previously, investigators reported a statistically significant and clinically meaningful improvement in EFS. These data suggest “that deploying immunotherapy early before surgery ... may be curative in some patients,” Dr. Arteaga said. The new data will allow the “robustness and consistency” of the earlier findings to be assessed.
But, he added, this is a “tough” treatment, which includes five drugs. “It’s the kitchen sink, and not everybody needs the kitchen sink. It’s important to refine these findings. Some patients may not need pembrolizumab, but some do.”
The second trial exploring pembrolizumab – KEYNOTE-355 (abstract GS1-02) – mirrors KEYNOTE-522 but in patients with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1.
Previously, investigators reported that pembrolizumab combined with chemotherapy showed statistically significant improvements in overall survival and PFS compared to placebo plus chemotherapy. At the 2021 SABCS, researchers will provide final study results, including outcomes in subgroups of patients by additional combined positive score cutoffs.
Metformin trial: ‘This is it’
Dr. Arteaga highlighted CCTGMA.32 (abstract GS1-08), a phase 3 randomized, placebo-controlled adjuvant trial of the diabetes drug metformin versus placebo in early breast cancer. Results of the primary efficacy analysis of the trial will be presented at the meeting.
The Canadian-led study seeks to determine if metformin can decrease breast cancer cell growth and work with cancer therapies to prevent disease recurrence. The study design calls for patients to take twice-daily oral metformin or placebo pills for up to 5 years in the absence of disease progression.
The primary outcome of the 3,500-plus patient trial is invasive disease-free survival in hormone receptor (ER and PgR) negative and positive (ER and/or PgR) subgroups.
“Metformin has actually been associated with improved survival [in breast cancer] in patients on chemotherapy. But we don’t know exactly how,” he said. “There’s never been a head-to-head comparison in the adjuvant setting [before]. This is it.”
TKI for breast cancer with brain mets
The SABCS codirector spotlighted an updated overall survival analysis of the randomized phase 3 PHOEBE trial (abstract GS3-02).
Previous research confirmed the superiority of pyrotinib, a novel TKI targeting HER1, HER2, and HER4, over lapatinib when given in combination with capecitabine in HER2-positive metastatic breast cancer.
In the United States, the lapatinib-capecitabine combination is “mostly used” in patients with HER2 metastatic disease and brain metastases who also undergo stereotactic radiation, Dr. Arteaga said.
This use has continued despite groundbreaking results from the HER2CLIMB trial, featuring the TKI tucatinib, he said.
As reported last year, adding tucatinib to trastuzumab and capecitabine in patients with HER2-positive breast cancer and brain metastases increased median overall survival from 12 months to 18.1 months. The results were called the first of their kind at that time.
The pyrotinib study may matter to American clinicians because pyrotinib is used mostly in China, not the United States, and this analysis suggests that pyrotinib could be part of the armamentarium in the United States, alongside tucatinib.
TKIs are like Coke and Pepsi, Dr. Arteaga said: “Similar but not identical.” Therefore, it is worth taking a look at the new study, he said. “There may be some benefit in having more than one [TKI] in the therapeutic armamentarium.”
Dr. Arteaga receives or has received grant support from Pfizer and Lilly and serves or has served in a scientific advisory role with Novartis, Lilly, TAIHO Oncology, Daiichi Sankyo, Merck, AstraZeneca, OrigiMed, Immunomedics, ARVINAS, Sanofi, Athenex, and the Susan G. Komen Foundation. He also holds minor stock options from Provista.
A version of this article first appeared on Medscape.com.
Dr. Arteaga, the meeting’s codirector, said the first-ever hybrid symposium will take place virtually from Dec. 7 to 10 as well as in person. Online availability appears to be a boon to attendance, with a record 9,325 registrants for the 2020 symposium, held only virtually because of the COVID-19 pandemic.
The meeting will have an app available, which can be accessed by searching “San Antonio Breast Cancer Symposium” (Google Play for Android, Apple for iOS) and downloading, or by going to www.core-apps.com/dl/sabcs from a desktop computer.
Dr. Arteaga provided a sneak peek of the most exciting research being presented at the upcoming meeting.
On the horizon for advanced breast cancer
A “very important” study of an investigational oral agent employed in heavily pretreated postmenopausal women with estrogen receptor–positive (ER+) advanced breast cancer headlines the meeting.
This international, multicenter trial could have “practice-changing implications,” Dr. Arteaga said in an interview.
The phase 3 EMERALD trial (abstract GS2-02) pits elacestrant, a selective estrogen receptor degrader (SERD), against standard endocrine therapy (fulvestrant or an aromatase inhibitor) in patients with metastatic breast cancer whose disease has progressed after treatment with at least one endocrine therapy and a CDK4/6 inhibitor.
The trial is important because many patients with breast cancer have estrogen receptor mutations, which are a “major mechanism of [drug] resistance” and thus progression on earlier therapy, Dr. Arteaga said.
Elacestrant is in good company among a plethora of oral SERDs under investigation in advanced breast cancer; however, currently, fulvestrant – which requires an intramuscular injection in the buttocks every month – is the only approved SERD.
“There’s plenty of preclinical data that suggest that these drugs [SERDs] may have activity against these mutant forms of the receptor, which occur in up to 40% of patients with advanced ER+ breast cancer,” he explained.
Researchers will present data on two primary outcome measures from the phase 3 trial: progression-free survival (PFS) based on mutations of the estrogen receptor 1 gene (ESR1-mut) and PFS in all subjects regardless of ESR1 status.
In addition to the EMERALD trial, PADA-1 (abstract GS3-05) is another important randomized, phase 3 trial focused on treating estrogen receptor mutations in patients with metastatic disease, said Dr. Arteaga.
The trial has enrolled patients with ER+ metastatic breast cancer who received an aromatase inhibitor (letrozole, anastrozole, or exemestane) and the CDK4/6 inhibitor palbociclib as first-line therapy.
In step 1 of the trial, approximately 1,000 patients were screened for circulating blood ESR1 mutation detection at regular intervals while being treated with palbociclib and an aromatase inhibitor in a continuous scheme until tumor progression or ESR1 mutation detection.
In step 2, up to 200 patients with a rising circulating ESR1 mutation and no tumor progression were randomized 1:1 to no change in therapy until tumor progression or to receive palbociclib plus fulvestrant until tumor progression.
The trial examines the safety and efficacy of “a clinical conundrum that we face” in this setting: whether or not to switch treatment from an aromatase inhibitor to fulvestrant while continuing a CDK4/6 inhibitor at the sign of mutation detection, Dr. Arteaga explained.
Refining who gets the ‘kitchen sink’
Dr. Arteaga highlighted two trials focused on the immune checkpoint inhibitor pembrolizumab.
The phase 3 KEYNOTE-522 study led to the approval of neoadjuvant pembrolizumab plus chemotherapy for early-stage triple-negative breast cancer (TNBC) in July 2021. At this year’s SABCS, researchers will present new data from KEYNOTE-522 (abstract GS1-01), representing final results from the trial’s event-free survival (EFS) outcome.
Previously, investigators reported a statistically significant and clinically meaningful improvement in EFS. These data suggest “that deploying immunotherapy early before surgery ... may be curative in some patients,” Dr. Arteaga said. The new data will allow the “robustness and consistency” of the earlier findings to be assessed.
But, he added, this is a “tough” treatment, which includes five drugs. “It’s the kitchen sink, and not everybody needs the kitchen sink. It’s important to refine these findings. Some patients may not need pembrolizumab, but some do.”
The second trial exploring pembrolizumab – KEYNOTE-355 (abstract GS1-02) – mirrors KEYNOTE-522 but in patients with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1.
Previously, investigators reported that pembrolizumab combined with chemotherapy showed statistically significant improvements in overall survival and PFS compared to placebo plus chemotherapy. At the 2021 SABCS, researchers will provide final study results, including outcomes in subgroups of patients by additional combined positive score cutoffs.
Metformin trial: ‘This is it’
Dr. Arteaga highlighted CCTGMA.32 (abstract GS1-08), a phase 3 randomized, placebo-controlled adjuvant trial of the diabetes drug metformin versus placebo in early breast cancer. Results of the primary efficacy analysis of the trial will be presented at the meeting.
The Canadian-led study seeks to determine if metformin can decrease breast cancer cell growth and work with cancer therapies to prevent disease recurrence. The study design calls for patients to take twice-daily oral metformin or placebo pills for up to 5 years in the absence of disease progression.
The primary outcome of the 3,500-plus patient trial is invasive disease-free survival in hormone receptor (ER and PgR) negative and positive (ER and/or PgR) subgroups.
“Metformin has actually been associated with improved survival [in breast cancer] in patients on chemotherapy. But we don’t know exactly how,” he said. “There’s never been a head-to-head comparison in the adjuvant setting [before]. This is it.”
TKI for breast cancer with brain mets
The SABCS codirector spotlighted an updated overall survival analysis of the randomized phase 3 PHOEBE trial (abstract GS3-02).
Previous research confirmed the superiority of pyrotinib, a novel TKI targeting HER1, HER2, and HER4, over lapatinib when given in combination with capecitabine in HER2-positive metastatic breast cancer.
In the United States, the lapatinib-capecitabine combination is “mostly used” in patients with HER2 metastatic disease and brain metastases who also undergo stereotactic radiation, Dr. Arteaga said.
This use has continued despite groundbreaking results from the HER2CLIMB trial, featuring the TKI tucatinib, he said.
As reported last year, adding tucatinib to trastuzumab and capecitabine in patients with HER2-positive breast cancer and brain metastases increased median overall survival from 12 months to 18.1 months. The results were called the first of their kind at that time.
The pyrotinib study may matter to American clinicians because pyrotinib is used mostly in China, not the United States, and this analysis suggests that pyrotinib could be part of the armamentarium in the United States, alongside tucatinib.
TKIs are like Coke and Pepsi, Dr. Arteaga said: “Similar but not identical.” Therefore, it is worth taking a look at the new study, he said. “There may be some benefit in having more than one [TKI] in the therapeutic armamentarium.”
Dr. Arteaga receives or has received grant support from Pfizer and Lilly and serves or has served in a scientific advisory role with Novartis, Lilly, TAIHO Oncology, Daiichi Sankyo, Merck, AstraZeneca, OrigiMed, Immunomedics, ARVINAS, Sanofi, Athenex, and the Susan G. Komen Foundation. He also holds minor stock options from Provista.
A version of this article first appeared on Medscape.com.
FROM SABCS 2021
After doc uproar, NCCN reverses prostate cancer guidance
After making a controversial change in September to a long-standing recommendation about the use of active surveillance in men with prostate cancer, the National Comprehensive Cancer Network (NCCN) has reversed course and reinstated its original advice, with a slight tweak.
The influential cancer organization, which is best known for its guidelines, now recommends that “most” men with low-risk prostate cancer be offered active surveillance as the lone “preferred” initial treatment option. This advice aligns closely with the group’s initial recommendation, published over a decade ago.
But controversy erupted in late September when the NCCN suddenly changed its tune on active surveillance, recommending that men with low-risk disease be managed with either active surveillance, radiation therapy, or surgery, with equal weight given to all three.
The new advice angered physicians who support the concept of active surveillance, which aims to avoid or delay treatment — and potentially life-changing side effects — until signs of disease progression.
The NCCN listened to the complaints.
On Nov. 30, the group largely reverted back to the original recommendation. In updated guidelines,
In an email sent to this news organization, Edward Schaeffer, MD, PhD, chair of the prostate cancer treatment panel, said that “the NCCN Prostate Cancer Panel recently convened” and “extensively revised the Principles of Active Surveillance and Observation.”
Dr. Schaeffer, who is from the Lurie Comprehensive Cancer Center of Northwestern University in Chicago, cited the heterogeneity across the low-risk disease group. Factors associated with an increased probability of near-term grade reclassification from low risk to higher risk include high PSA density, a high number of positive cores (≥ 3), high genomic risk (from tissue-based molecular tumor analysis), and/or a known BRCA2 germline mutation, he added.
Urologists cheered the NCCN’s reversal on Twitter.
“Big news! NCCN guidelines updated again — active surveillance is ‘preferred for most patients’ with low risk prostate cancer and life expectancy >=10 years,” tweeted Stacy Loeb of NYU Langone in New York City.
“Very exciting if true,” tweeted Matthew Cooperberg, MD, of University of California San Francisco, who was one of the most vocal critics of the NCCN’s change in September, calling that move a “step backward” that would likely lead to overtreatment.
A version of this article first appeared on Medscape.com.
After making a controversial change in September to a long-standing recommendation about the use of active surveillance in men with prostate cancer, the National Comprehensive Cancer Network (NCCN) has reversed course and reinstated its original advice, with a slight tweak.
The influential cancer organization, which is best known for its guidelines, now recommends that “most” men with low-risk prostate cancer be offered active surveillance as the lone “preferred” initial treatment option. This advice aligns closely with the group’s initial recommendation, published over a decade ago.
But controversy erupted in late September when the NCCN suddenly changed its tune on active surveillance, recommending that men with low-risk disease be managed with either active surveillance, radiation therapy, or surgery, with equal weight given to all three.
The new advice angered physicians who support the concept of active surveillance, which aims to avoid or delay treatment — and potentially life-changing side effects — until signs of disease progression.
The NCCN listened to the complaints.
On Nov. 30, the group largely reverted back to the original recommendation. In updated guidelines,
In an email sent to this news organization, Edward Schaeffer, MD, PhD, chair of the prostate cancer treatment panel, said that “the NCCN Prostate Cancer Panel recently convened” and “extensively revised the Principles of Active Surveillance and Observation.”
Dr. Schaeffer, who is from the Lurie Comprehensive Cancer Center of Northwestern University in Chicago, cited the heterogeneity across the low-risk disease group. Factors associated with an increased probability of near-term grade reclassification from low risk to higher risk include high PSA density, a high number of positive cores (≥ 3), high genomic risk (from tissue-based molecular tumor analysis), and/or a known BRCA2 germline mutation, he added.
Urologists cheered the NCCN’s reversal on Twitter.
“Big news! NCCN guidelines updated again — active surveillance is ‘preferred for most patients’ with low risk prostate cancer and life expectancy >=10 years,” tweeted Stacy Loeb of NYU Langone in New York City.
“Very exciting if true,” tweeted Matthew Cooperberg, MD, of University of California San Francisco, who was one of the most vocal critics of the NCCN’s change in September, calling that move a “step backward” that would likely lead to overtreatment.
A version of this article first appeared on Medscape.com.
After making a controversial change in September to a long-standing recommendation about the use of active surveillance in men with prostate cancer, the National Comprehensive Cancer Network (NCCN) has reversed course and reinstated its original advice, with a slight tweak.
The influential cancer organization, which is best known for its guidelines, now recommends that “most” men with low-risk prostate cancer be offered active surveillance as the lone “preferred” initial treatment option. This advice aligns closely with the group’s initial recommendation, published over a decade ago.
But controversy erupted in late September when the NCCN suddenly changed its tune on active surveillance, recommending that men with low-risk disease be managed with either active surveillance, radiation therapy, or surgery, with equal weight given to all three.
The new advice angered physicians who support the concept of active surveillance, which aims to avoid or delay treatment — and potentially life-changing side effects — until signs of disease progression.
The NCCN listened to the complaints.
On Nov. 30, the group largely reverted back to the original recommendation. In updated guidelines,
In an email sent to this news organization, Edward Schaeffer, MD, PhD, chair of the prostate cancer treatment panel, said that “the NCCN Prostate Cancer Panel recently convened” and “extensively revised the Principles of Active Surveillance and Observation.”
Dr. Schaeffer, who is from the Lurie Comprehensive Cancer Center of Northwestern University in Chicago, cited the heterogeneity across the low-risk disease group. Factors associated with an increased probability of near-term grade reclassification from low risk to higher risk include high PSA density, a high number of positive cores (≥ 3), high genomic risk (from tissue-based molecular tumor analysis), and/or a known BRCA2 germline mutation, he added.
Urologists cheered the NCCN’s reversal on Twitter.
“Big news! NCCN guidelines updated again — active surveillance is ‘preferred for most patients’ with low risk prostate cancer and life expectancy >=10 years,” tweeted Stacy Loeb of NYU Langone in New York City.
“Very exciting if true,” tweeted Matthew Cooperberg, MD, of University of California San Francisco, who was one of the most vocal critics of the NCCN’s change in September, calling that move a “step backward” that would likely lead to overtreatment.
A version of this article first appeared on Medscape.com.
FDA approves imaging drug for detecting ovarian cancer lesions
The new drug “is designed to improve the ability to locate additional ovarian cancerous tissue that is normally difficult to detect during surgery,” according to the agency.
Pafolacianine, administered via intravenous injection prior to surgery, is the first FDA-approved tumor-targeted fluorescent agent for ovarian cancer.
In a press statement, drug inventor Philip Low, PhD, of Purdue University in West Lafayette, Ind., said the agent causes ovarian cancer lesions to “light up like stars against a night sky.”
Improving detection of ovarian cancer lesions is critical given that ovarian cancer is one of the “deadliest of all female reproductive system cancers,” according to the American Cancer Society. The organization estimates that there will be more than 21,000 new cases and more than 13,000 deaths in 2021.
Currently, surgeons use preoperative imaging as well as visual inspection of tumors under normal light and examination by touch to identify ovarian cancer lesions.
Pafolacianine offers a new tool to enhance surgeons’ ability “to identify deadly ovarian tumors that may otherwise go undetected,” Alex Gorovets, MD, deputy director of the office of specialty medicine in the FDA’s Center for Drug Evaluation and Research, said in a press statement.
Ovarian cancer often causes the body to overproduce the folate receptor protein in cell membranes. Pafolacianine, employed with a near-infrared fluorescence imaging system cleared by the FDA for use alongside the drug, binds to and illuminates these proteins under fluorescent light, “boosting surgeons’ ability to identify the cancerous tissue,” the agency in a statement.
The safety and effectiveness of pafolacianine was evaluated in a randomized, multi-center, open-label study of women diagnosed with ovarian cancer or with high clinical suspicion of ovarian cancer. Of the 134 women undergoing surgery who received a dose of pafolacianine and were evaluated under both normal and fluorescent light, 26.9% had at least one cancerous lesion detected that was not observed by standard visual or tactile inspection.
The most common side effects of pafolacianine were infusion-related reactions, including nausea, vomiting, abdominal pain, flushing, dyspepsia, chest discomfort, itching, and hypersensitivity.
Pafolacianine may cause fetal harm when administered to a pregnant woman. The use of folate, folic acid, or folate-containing supplements should be avoided within 48 hours before administration of pafolacianine.
The FDA also cautioned about the possible risk of image interpretation errors, including false negatives and false positives, with the use of the new drug and near-infrared fluorescence imaging system.
The FDA previously granted pafolacianine orphan-drug, priority, and fast track designations.
A version of this article first appeared on Medscape.com.
The new drug “is designed to improve the ability to locate additional ovarian cancerous tissue that is normally difficult to detect during surgery,” according to the agency.
Pafolacianine, administered via intravenous injection prior to surgery, is the first FDA-approved tumor-targeted fluorescent agent for ovarian cancer.
In a press statement, drug inventor Philip Low, PhD, of Purdue University in West Lafayette, Ind., said the agent causes ovarian cancer lesions to “light up like stars against a night sky.”
Improving detection of ovarian cancer lesions is critical given that ovarian cancer is one of the “deadliest of all female reproductive system cancers,” according to the American Cancer Society. The organization estimates that there will be more than 21,000 new cases and more than 13,000 deaths in 2021.
Currently, surgeons use preoperative imaging as well as visual inspection of tumors under normal light and examination by touch to identify ovarian cancer lesions.
Pafolacianine offers a new tool to enhance surgeons’ ability “to identify deadly ovarian tumors that may otherwise go undetected,” Alex Gorovets, MD, deputy director of the office of specialty medicine in the FDA’s Center for Drug Evaluation and Research, said in a press statement.
Ovarian cancer often causes the body to overproduce the folate receptor protein in cell membranes. Pafolacianine, employed with a near-infrared fluorescence imaging system cleared by the FDA for use alongside the drug, binds to and illuminates these proteins under fluorescent light, “boosting surgeons’ ability to identify the cancerous tissue,” the agency in a statement.
The safety and effectiveness of pafolacianine was evaluated in a randomized, multi-center, open-label study of women diagnosed with ovarian cancer or with high clinical suspicion of ovarian cancer. Of the 134 women undergoing surgery who received a dose of pafolacianine and were evaluated under both normal and fluorescent light, 26.9% had at least one cancerous lesion detected that was not observed by standard visual or tactile inspection.
The most common side effects of pafolacianine were infusion-related reactions, including nausea, vomiting, abdominal pain, flushing, dyspepsia, chest discomfort, itching, and hypersensitivity.
Pafolacianine may cause fetal harm when administered to a pregnant woman. The use of folate, folic acid, or folate-containing supplements should be avoided within 48 hours before administration of pafolacianine.
The FDA also cautioned about the possible risk of image interpretation errors, including false negatives and false positives, with the use of the new drug and near-infrared fluorescence imaging system.
The FDA previously granted pafolacianine orphan-drug, priority, and fast track designations.
A version of this article first appeared on Medscape.com.
The new drug “is designed to improve the ability to locate additional ovarian cancerous tissue that is normally difficult to detect during surgery,” according to the agency.
Pafolacianine, administered via intravenous injection prior to surgery, is the first FDA-approved tumor-targeted fluorescent agent for ovarian cancer.
In a press statement, drug inventor Philip Low, PhD, of Purdue University in West Lafayette, Ind., said the agent causes ovarian cancer lesions to “light up like stars against a night sky.”
Improving detection of ovarian cancer lesions is critical given that ovarian cancer is one of the “deadliest of all female reproductive system cancers,” according to the American Cancer Society. The organization estimates that there will be more than 21,000 new cases and more than 13,000 deaths in 2021.
Currently, surgeons use preoperative imaging as well as visual inspection of tumors under normal light and examination by touch to identify ovarian cancer lesions.
Pafolacianine offers a new tool to enhance surgeons’ ability “to identify deadly ovarian tumors that may otherwise go undetected,” Alex Gorovets, MD, deputy director of the office of specialty medicine in the FDA’s Center for Drug Evaluation and Research, said in a press statement.
Ovarian cancer often causes the body to overproduce the folate receptor protein in cell membranes. Pafolacianine, employed with a near-infrared fluorescence imaging system cleared by the FDA for use alongside the drug, binds to and illuminates these proteins under fluorescent light, “boosting surgeons’ ability to identify the cancerous tissue,” the agency in a statement.
The safety and effectiveness of pafolacianine was evaluated in a randomized, multi-center, open-label study of women diagnosed with ovarian cancer or with high clinical suspicion of ovarian cancer. Of the 134 women undergoing surgery who received a dose of pafolacianine and were evaluated under both normal and fluorescent light, 26.9% had at least one cancerous lesion detected that was not observed by standard visual or tactile inspection.
The most common side effects of pafolacianine were infusion-related reactions, including nausea, vomiting, abdominal pain, flushing, dyspepsia, chest discomfort, itching, and hypersensitivity.
Pafolacianine may cause fetal harm when administered to a pregnant woman. The use of folate, folic acid, or folate-containing supplements should be avoided within 48 hours before administration of pafolacianine.
The FDA also cautioned about the possible risk of image interpretation errors, including false negatives and false positives, with the use of the new drug and near-infrared fluorescence imaging system.
The FDA previously granted pafolacianine orphan-drug, priority, and fast track designations.
A version of this article first appeared on Medscape.com.
EU panel endorses first-of-its-kind lung cancer drug
At its November meeting, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) endorsed the novel oral therapy sotorasib (Lumykras). The indication is use in the treatment of adults with advanced NSCLC with a KRAS G12C mutation who have progressed after at least one prior line of systemic therapy.
Sotorasib is an inhibitor of KRAS G12C, an oncogenic driver of tumorigenesis. The drug blocks tumor cell signaling and survival, inhibits cell growth, and selectively promotes apoptosis in tumors harboring KRAS G12C, according to the CHMP.
KRAS mutations are the most common mutations in NSCLC tumors, but for a long time appeared to be resistant to drug therapy.
The KRAS G12C mutation occurs in about 13% of NSCLC mutations.
When clinical data on sotorasib were presented at the 2020 World Conference on Lung Cancer, lung cancer experts greeted the results enthusiastically.
“This is a historic milestone in lung cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need,” Bob Li, MD, PhD, MPH, of Memorial Sloan Kettering Cancer Center in New York City, said at the time.
The drug was approved by the U.S. Food and Drug Administration in May based on a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy.
The FDA approval was based on an overall response rate of 36%, the study’s primary outcome. Of the patients who responded, 58% had a duration of response of 6 months or longer.
The EMA says its recommendation for approval is based on objective response rate and response duration data.
The most common side effects of sotorasib are diarrhea, nausea, fatigue, increased aspartate aminotransferase, and arthralgia said the CHMP.
A version of this article first appeared on Medscape.com.
At its November meeting, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) endorsed the novel oral therapy sotorasib (Lumykras). The indication is use in the treatment of adults with advanced NSCLC with a KRAS G12C mutation who have progressed after at least one prior line of systemic therapy.
Sotorasib is an inhibitor of KRAS G12C, an oncogenic driver of tumorigenesis. The drug blocks tumor cell signaling and survival, inhibits cell growth, and selectively promotes apoptosis in tumors harboring KRAS G12C, according to the CHMP.
KRAS mutations are the most common mutations in NSCLC tumors, but for a long time appeared to be resistant to drug therapy.
The KRAS G12C mutation occurs in about 13% of NSCLC mutations.
When clinical data on sotorasib were presented at the 2020 World Conference on Lung Cancer, lung cancer experts greeted the results enthusiastically.
“This is a historic milestone in lung cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need,” Bob Li, MD, PhD, MPH, of Memorial Sloan Kettering Cancer Center in New York City, said at the time.
The drug was approved by the U.S. Food and Drug Administration in May based on a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy.
The FDA approval was based on an overall response rate of 36%, the study’s primary outcome. Of the patients who responded, 58% had a duration of response of 6 months or longer.
The EMA says its recommendation for approval is based on objective response rate and response duration data.
The most common side effects of sotorasib are diarrhea, nausea, fatigue, increased aspartate aminotransferase, and arthralgia said the CHMP.
A version of this article first appeared on Medscape.com.
At its November meeting, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) endorsed the novel oral therapy sotorasib (Lumykras). The indication is use in the treatment of adults with advanced NSCLC with a KRAS G12C mutation who have progressed after at least one prior line of systemic therapy.
Sotorasib is an inhibitor of KRAS G12C, an oncogenic driver of tumorigenesis. The drug blocks tumor cell signaling and survival, inhibits cell growth, and selectively promotes apoptosis in tumors harboring KRAS G12C, according to the CHMP.
KRAS mutations are the most common mutations in NSCLC tumors, but for a long time appeared to be resistant to drug therapy.
The KRAS G12C mutation occurs in about 13% of NSCLC mutations.
When clinical data on sotorasib were presented at the 2020 World Conference on Lung Cancer, lung cancer experts greeted the results enthusiastically.
“This is a historic milestone in lung cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need,” Bob Li, MD, PhD, MPH, of Memorial Sloan Kettering Cancer Center in New York City, said at the time.
The drug was approved by the U.S. Food and Drug Administration in May based on a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy.
The FDA approval was based on an overall response rate of 36%, the study’s primary outcome. Of the patients who responded, 58% had a duration of response of 6 months or longer.
The EMA says its recommendation for approval is based on objective response rate and response duration data.
The most common side effects of sotorasib are diarrhea, nausea, fatigue, increased aspartate aminotransferase, and arthralgia said the CHMP.
A version of this article first appeared on Medscape.com.
Shock, disbelief as NCCN changes prostate cancer guidance
For over a decade, the influential National Comprehensive Cancer Network (NCCN) has been recommending that men with low-risk prostate cancer be offered active surveillance as the lone “preferred” initial treatment option.
But the NCCN has now reversed this long-standing recommendation in the latest revision of its prostate cancer guideline.
The organization now recommends that low-risk disease be managed with either active surveillance or radiation therapy or surgery, with equal weight given to all three of these initial options.
The complaints were voiced in unusually blunt and strong language for physicians.
“This is a terrible step back that impacts every urologist,” commented John Griffith, MD, of Hartford Healthcare, who practices in New Britain, Conn.
Dr. Griffith explained that he prints out the NCCN guidance with “every patient newly diagnosed” and that the preferred designation is a “huge help” in reassuring them about not treating low-risk disease initially.
In a Twitter thread, Benjamin Davies, MD, of the University of Pittsburgh, facetiously wondered if a time warp was at play: “To suggest for a millisecond that active surveillance isn’t the preferred method for low-risk men is bizarre thinking ... Is this 1980?”
“I’m baffled,” said Brian Chapin, MD, of MD Anderson Cancer Center, Houston, in another Twitter thread.
“This is ludicrous,” said Andrew Vickers, PhD, of Memorial Sloan Kettering Cancer Center in New York City in a tweet.
Alexander Kutikov, MD, of Fox Chase Cancer Center in Philadelphia, commented on Twitter that the change “seems off the rails…a bit stunned by this.”
Matthew Cooperberg, MD, of the University of California San Francisco, and Minhaj Siddiqui, MD, of the University of Maryland in Baltimore both called the move a “step backward.”
Many others also expressed disappointment in the NCCN, whose guidelines are hugely influential because of the role they play clinically as well as with payors and the legal system.
“A huge setback & frankly a disgrace for @NCCN and its processes,” commented Fox Chase’s Dr. Kutikov.
Stacy Loeb, MD, of NYU Langone Health in New York City, suggested the new guidance may stunt use of active surveillance in the United States. She tweeted: “The updated NCCN guideline certainly won’t help the lagging and heterogenous uptake of active surveillance in the U.S. We should be carefully expanding the pool for active surveillance, not narrowing it.”
The purpose of active surveillance is to avoid adverse events from treatment, which can be life-changing as they include incontinence and erectile dysfunction.
The rationale is that many men with low-risk prostate cancer may not need treatment for their disease, as the disease may be slow-growing and may never threaten their life. With active surveillance, men are instead monitored with blood tests, scans, and biopsies to watch for worsening disease, and treated only when there are signs of disease progression.
This active surveillance approach has grown in acceptance among American patients since 2010.
The concern now is that the change in guidance from the NCCN will lead to a reduction in active surveillance, and an increase in initial treatment with surgery and radiotherapy for low-risk disease, which is considered by many to be “overtreatment’ of this disease and may not be medically necessary.
For example, UCSF’s Dr. Cooperberg said he feared that the changed guidance “will be used by urologists and radiation oncologists to justify overtreatment of low-risk disease.”
Dr. Kutikov agreed but described that possibility differently, citing the risk of lawsuits. He observed that without the NCCN’s “medico-legal buffer” of active surveillance as the preferred initial treatment, there are “further incentives” for overtreatment.
The new NCCN guidance also conflicts with the American Urological Association’s guidelines and dissolves what was once a mostly united front from the two major organizations on active surveillance and low-risk disease.
The AUA Guideline reads: “Clinicians should recommend active surveillance as the preferable care option for most low-risk localized prostate cancer patients (Moderate Recommendation; Evidence Level: Grade B)
Patients protest change in wording
Not surprisingly, the revised NCCN guidance was criticized by multiple patient advocacy groups, including Active Surveillance Patients International (ASPI), which wrote a letter to the NCCN protesting the change.
In that letter, the ASPI writes that active surveillance is now chosen as the initial approach for low-risk prostate cancer in about 90% of cases in some European nations, and in about 50% of cases in the United States. It also warns that eliminating the word “preferred” from the NCCN guidelines represents a retreat, and “will have repercussions far beyond what we may first conceive.”
“Active surveillance should be the preferred choice to preserve quality of life for men with low-risk cancer,” the advocacy group states. “The PIVOT trials indicate for low-risk disease there is basically no advantage to intervention. Why would one risk the side effects if they knew that?”
Why now?
The NCCN’s move to alter its low-risk prostate cancer guidance is especially striking because, 11 years ago, the NCCN broke new ground in recommending active surveillance as the sole initial treatment option for low-risk men. (It was also the first guidelines group to recommend the same for very low-risk men.)
So why the change now? This news organization requested, but did not receive, comment from the NCCN and its chair of the prostate cancer panel, Edward Schaeffer, MD, of Northwestern University in Chicago.
However, on Twitter, Dr. Schaeffer hinted at what had turned the tables for the NCCN panel – the risk that, over time, some men with low-risk disease who are on active surveillance are reclassified on biopsy as having a higher risk.
He highlighted a 2020 study on that very subject from the University of California, San Francisco, published in the Journal of Urology. Those authors concluded that: “Given the heterogeneity of the disease, some tumors characterized as low risk may merit early treatment while others may be followed much less intensely over some time interval.”
Dr. Schaeffer tweeted: “I think this nicely sums up the low-risk space ...”
Experts reacting to Dr. Schaeffer’s tweet were not swayed.
Looking at additional measures such as genomic scores and PSA density, as advocated by Dr. Schaeffer via the posted 2020 study, is good for assessing individual risk, “but still, active surveillance is the preferred option for low risk,” said MD Anderson’s Dr. Chapin.
UCSF’s Dr. Cooperberg, who was a co-author on that 2020 Journal of Urology paper, commented that the university’s urology department had “spent the past quarter century arguing active surveillance is ‘preferred’ for almost all low risk [disease]!”
“Many on active surveillance need treatment someday, but that does not justify immediate overtreatment,” he concluded.
A version of this article first appeared on Medscape.com.
For over a decade, the influential National Comprehensive Cancer Network (NCCN) has been recommending that men with low-risk prostate cancer be offered active surveillance as the lone “preferred” initial treatment option.
But the NCCN has now reversed this long-standing recommendation in the latest revision of its prostate cancer guideline.
The organization now recommends that low-risk disease be managed with either active surveillance or radiation therapy or surgery, with equal weight given to all three of these initial options.
The complaints were voiced in unusually blunt and strong language for physicians.
“This is a terrible step back that impacts every urologist,” commented John Griffith, MD, of Hartford Healthcare, who practices in New Britain, Conn.
Dr. Griffith explained that he prints out the NCCN guidance with “every patient newly diagnosed” and that the preferred designation is a “huge help” in reassuring them about not treating low-risk disease initially.
In a Twitter thread, Benjamin Davies, MD, of the University of Pittsburgh, facetiously wondered if a time warp was at play: “To suggest for a millisecond that active surveillance isn’t the preferred method for low-risk men is bizarre thinking ... Is this 1980?”
“I’m baffled,” said Brian Chapin, MD, of MD Anderson Cancer Center, Houston, in another Twitter thread.
“This is ludicrous,” said Andrew Vickers, PhD, of Memorial Sloan Kettering Cancer Center in New York City in a tweet.
Alexander Kutikov, MD, of Fox Chase Cancer Center in Philadelphia, commented on Twitter that the change “seems off the rails…a bit stunned by this.”
Matthew Cooperberg, MD, of the University of California San Francisco, and Minhaj Siddiqui, MD, of the University of Maryland in Baltimore both called the move a “step backward.”
Many others also expressed disappointment in the NCCN, whose guidelines are hugely influential because of the role they play clinically as well as with payors and the legal system.
“A huge setback & frankly a disgrace for @NCCN and its processes,” commented Fox Chase’s Dr. Kutikov.
Stacy Loeb, MD, of NYU Langone Health in New York City, suggested the new guidance may stunt use of active surveillance in the United States. She tweeted: “The updated NCCN guideline certainly won’t help the lagging and heterogenous uptake of active surveillance in the U.S. We should be carefully expanding the pool for active surveillance, not narrowing it.”
The purpose of active surveillance is to avoid adverse events from treatment, which can be life-changing as they include incontinence and erectile dysfunction.
The rationale is that many men with low-risk prostate cancer may not need treatment for their disease, as the disease may be slow-growing and may never threaten their life. With active surveillance, men are instead monitored with blood tests, scans, and biopsies to watch for worsening disease, and treated only when there are signs of disease progression.
This active surveillance approach has grown in acceptance among American patients since 2010.
The concern now is that the change in guidance from the NCCN will lead to a reduction in active surveillance, and an increase in initial treatment with surgery and radiotherapy for low-risk disease, which is considered by many to be “overtreatment’ of this disease and may not be medically necessary.
For example, UCSF’s Dr. Cooperberg said he feared that the changed guidance “will be used by urologists and radiation oncologists to justify overtreatment of low-risk disease.”
Dr. Kutikov agreed but described that possibility differently, citing the risk of lawsuits. He observed that without the NCCN’s “medico-legal buffer” of active surveillance as the preferred initial treatment, there are “further incentives” for overtreatment.
The new NCCN guidance also conflicts with the American Urological Association’s guidelines and dissolves what was once a mostly united front from the two major organizations on active surveillance and low-risk disease.
The AUA Guideline reads: “Clinicians should recommend active surveillance as the preferable care option for most low-risk localized prostate cancer patients (Moderate Recommendation; Evidence Level: Grade B)
Patients protest change in wording
Not surprisingly, the revised NCCN guidance was criticized by multiple patient advocacy groups, including Active Surveillance Patients International (ASPI), which wrote a letter to the NCCN protesting the change.
In that letter, the ASPI writes that active surveillance is now chosen as the initial approach for low-risk prostate cancer in about 90% of cases in some European nations, and in about 50% of cases in the United States. It also warns that eliminating the word “preferred” from the NCCN guidelines represents a retreat, and “will have repercussions far beyond what we may first conceive.”
“Active surveillance should be the preferred choice to preserve quality of life for men with low-risk cancer,” the advocacy group states. “The PIVOT trials indicate for low-risk disease there is basically no advantage to intervention. Why would one risk the side effects if they knew that?”
Why now?
The NCCN’s move to alter its low-risk prostate cancer guidance is especially striking because, 11 years ago, the NCCN broke new ground in recommending active surveillance as the sole initial treatment option for low-risk men. (It was also the first guidelines group to recommend the same for very low-risk men.)
So why the change now? This news organization requested, but did not receive, comment from the NCCN and its chair of the prostate cancer panel, Edward Schaeffer, MD, of Northwestern University in Chicago.
However, on Twitter, Dr. Schaeffer hinted at what had turned the tables for the NCCN panel – the risk that, over time, some men with low-risk disease who are on active surveillance are reclassified on biopsy as having a higher risk.
He highlighted a 2020 study on that very subject from the University of California, San Francisco, published in the Journal of Urology. Those authors concluded that: “Given the heterogeneity of the disease, some tumors characterized as low risk may merit early treatment while others may be followed much less intensely over some time interval.”
Dr. Schaeffer tweeted: “I think this nicely sums up the low-risk space ...”
Experts reacting to Dr. Schaeffer’s tweet were not swayed.
Looking at additional measures such as genomic scores and PSA density, as advocated by Dr. Schaeffer via the posted 2020 study, is good for assessing individual risk, “but still, active surveillance is the preferred option for low risk,” said MD Anderson’s Dr. Chapin.
UCSF’s Dr. Cooperberg, who was a co-author on that 2020 Journal of Urology paper, commented that the university’s urology department had “spent the past quarter century arguing active surveillance is ‘preferred’ for almost all low risk [disease]!”
“Many on active surveillance need treatment someday, but that does not justify immediate overtreatment,” he concluded.
A version of this article first appeared on Medscape.com.
For over a decade, the influential National Comprehensive Cancer Network (NCCN) has been recommending that men with low-risk prostate cancer be offered active surveillance as the lone “preferred” initial treatment option.
But the NCCN has now reversed this long-standing recommendation in the latest revision of its prostate cancer guideline.
The organization now recommends that low-risk disease be managed with either active surveillance or radiation therapy or surgery, with equal weight given to all three of these initial options.
The complaints were voiced in unusually blunt and strong language for physicians.
“This is a terrible step back that impacts every urologist,” commented John Griffith, MD, of Hartford Healthcare, who practices in New Britain, Conn.
Dr. Griffith explained that he prints out the NCCN guidance with “every patient newly diagnosed” and that the preferred designation is a “huge help” in reassuring them about not treating low-risk disease initially.
In a Twitter thread, Benjamin Davies, MD, of the University of Pittsburgh, facetiously wondered if a time warp was at play: “To suggest for a millisecond that active surveillance isn’t the preferred method for low-risk men is bizarre thinking ... Is this 1980?”
“I’m baffled,” said Brian Chapin, MD, of MD Anderson Cancer Center, Houston, in another Twitter thread.
“This is ludicrous,” said Andrew Vickers, PhD, of Memorial Sloan Kettering Cancer Center in New York City in a tweet.
Alexander Kutikov, MD, of Fox Chase Cancer Center in Philadelphia, commented on Twitter that the change “seems off the rails…a bit stunned by this.”
Matthew Cooperberg, MD, of the University of California San Francisco, and Minhaj Siddiqui, MD, of the University of Maryland in Baltimore both called the move a “step backward.”
Many others also expressed disappointment in the NCCN, whose guidelines are hugely influential because of the role they play clinically as well as with payors and the legal system.
“A huge setback & frankly a disgrace for @NCCN and its processes,” commented Fox Chase’s Dr. Kutikov.
Stacy Loeb, MD, of NYU Langone Health in New York City, suggested the new guidance may stunt use of active surveillance in the United States. She tweeted: “The updated NCCN guideline certainly won’t help the lagging and heterogenous uptake of active surveillance in the U.S. We should be carefully expanding the pool for active surveillance, not narrowing it.”
The purpose of active surveillance is to avoid adverse events from treatment, which can be life-changing as they include incontinence and erectile dysfunction.
The rationale is that many men with low-risk prostate cancer may not need treatment for their disease, as the disease may be slow-growing and may never threaten their life. With active surveillance, men are instead monitored with blood tests, scans, and biopsies to watch for worsening disease, and treated only when there are signs of disease progression.
This active surveillance approach has grown in acceptance among American patients since 2010.
The concern now is that the change in guidance from the NCCN will lead to a reduction in active surveillance, and an increase in initial treatment with surgery and radiotherapy for low-risk disease, which is considered by many to be “overtreatment’ of this disease and may not be medically necessary.
For example, UCSF’s Dr. Cooperberg said he feared that the changed guidance “will be used by urologists and radiation oncologists to justify overtreatment of low-risk disease.”
Dr. Kutikov agreed but described that possibility differently, citing the risk of lawsuits. He observed that without the NCCN’s “medico-legal buffer” of active surveillance as the preferred initial treatment, there are “further incentives” for overtreatment.
The new NCCN guidance also conflicts with the American Urological Association’s guidelines and dissolves what was once a mostly united front from the two major organizations on active surveillance and low-risk disease.
The AUA Guideline reads: “Clinicians should recommend active surveillance as the preferable care option for most low-risk localized prostate cancer patients (Moderate Recommendation; Evidence Level: Grade B)
Patients protest change in wording
Not surprisingly, the revised NCCN guidance was criticized by multiple patient advocacy groups, including Active Surveillance Patients International (ASPI), which wrote a letter to the NCCN protesting the change.
In that letter, the ASPI writes that active surveillance is now chosen as the initial approach for low-risk prostate cancer in about 90% of cases in some European nations, and in about 50% of cases in the United States. It also warns that eliminating the word “preferred” from the NCCN guidelines represents a retreat, and “will have repercussions far beyond what we may first conceive.”
“Active surveillance should be the preferred choice to preserve quality of life for men with low-risk cancer,” the advocacy group states. “The PIVOT trials indicate for low-risk disease there is basically no advantage to intervention. Why would one risk the side effects if they knew that?”
Why now?
The NCCN’s move to alter its low-risk prostate cancer guidance is especially striking because, 11 years ago, the NCCN broke new ground in recommending active surveillance as the sole initial treatment option for low-risk men. (It was also the first guidelines group to recommend the same for very low-risk men.)
So why the change now? This news organization requested, but did not receive, comment from the NCCN and its chair of the prostate cancer panel, Edward Schaeffer, MD, of Northwestern University in Chicago.
However, on Twitter, Dr. Schaeffer hinted at what had turned the tables for the NCCN panel – the risk that, over time, some men with low-risk disease who are on active surveillance are reclassified on biopsy as having a higher risk.
He highlighted a 2020 study on that very subject from the University of California, San Francisco, published in the Journal of Urology. Those authors concluded that: “Given the heterogeneity of the disease, some tumors characterized as low risk may merit early treatment while others may be followed much less intensely over some time interval.”
Dr. Schaeffer tweeted: “I think this nicely sums up the low-risk space ...”
Experts reacting to Dr. Schaeffer’s tweet were not swayed.
Looking at additional measures such as genomic scores and PSA density, as advocated by Dr. Schaeffer via the posted 2020 study, is good for assessing individual risk, “but still, active surveillance is the preferred option for low risk,” said MD Anderson’s Dr. Chapin.
UCSF’s Dr. Cooperberg, who was a co-author on that 2020 Journal of Urology paper, commented that the university’s urology department had “spent the past quarter century arguing active surveillance is ‘preferred’ for almost all low risk [disease]!”
“Many on active surveillance need treatment someday, but that does not justify immediate overtreatment,” he concluded.
A version of this article first appeared on Medscape.com.
NCI mammography trial mostly a ‘waste,’ says expert
Funding for this trial is largely misspent money, it may produce misleading results, and it should be abandoned, he says.
Dr. Kopans has been an outspoken critic of the trial, describing it as a “huge waste of money” in comments made last year. Now he has set out his criticisms of the trial in an essay published in the October issue of Clinical Imaging, which outlines his objections and concerns for the first time in a peer-reviewed journal.
The Tomosynthesis Mammographic Imaging Screening Trial (TMIST) is comparing digital breast tomosynthesis (DBT), also known as 3-D mammography, with the older 2-D technology or full-field digital mammography (FFDM).
Dr. Kopans coined the term DBT and formerly held a now-expired patent on the first version of this technology.
“It could be argued that the imaging part of TMIST is a waste of valuable resources,” he writes in the essay.
The “imaging part” of the trial refers to the primary outcome measure and driving purpose of the trial, which is designed to learn which technology is better at finding – and reducing the rate of – potentially lethal “advanced” cancers.
These cancers include larger HER2-positive and triple-negative malignancies; those associated with positive nodes; and metastatic disease. These malignancies correlate with breast cancer mortality, TMIST’s principal investigator Etta Pisano, MD, of the American College of Radiology, has said in the past.
However, Dr. Kopans says that this surrogate endpoint is problematic. “TMIST will only investigate whether or not digital breast tomography results in a decline in advanced cancers, ignoring the fact that many women still die from cancers that are not advanced at the time of diagnosis,” he writes.
“Clearly reducing the rate of advanced cancers is not the only way that early detection saves lives. Lives are also saved by finding cancers at a smaller size within stages,” Dr. Kopans writes. He adds that DBT has been proven in observational cohort studies to find more smaller breast cancers than FFDM.
Dr. Kopans’ opinion that TMIST is largely a waste of resources is not shared by the National Cancer Institute. “We feel strongly that TMIST is a critical study,” an NCI spokesperson told this news organization.
Study power concerns
Another concern is that TMIST “may be underpowered,” Dr. Kopans writes. That concern arises in part from a recent review of TMIST by an advisory committee (that was prompted by low patient accrual rates), which proposed reducing the size of the trial. Dr. Kopans says this would result in “a reduction of the planned power of the trial.”
The NCI says that reducing the study size has been discussed but has not yet been implemented. “Any reduction in size would, of course, have appropriate statistical considerations in mind,” according to the NCI spokesperson.
Dr. Kopans’ concern about statistical power extends beyond downsizing the trial. An advanced cancer in TMIST is counted “if it occurs at any time while the participant is on study,” according to the NCI. Dr. Kopans says that is a problem.
“Since DBT cannot have any effect on advanced cancers in the prevalence year (they are already there), data from the first year (prevalence cancers are likely the largest number) will be unusable, and if used will, inappropriately, dilute the results,” he writes.
Dr. Kopans hopes that the investigators address the statistical power issues with the trial because, if not, “its results may be grossly misleading.”
American radiology practice
Dr. Kopans praises one aspect of TMIST – the trial’s effort to create a repository of blood and oral swab specimens, along with participant genetic data. The goal, say TMIST investigators, is to individualize or optimize screening strategies by tying molecular data to clinical outcomes in the trial.
However, apart from that one aspect, Dr. Kopans is highly critical of the trial.
It is now too late to compare the two technologies, he suggests, as DBT is already replacing FFDM for breast cancer screening in the U.S.
He notes that 76% of mammography facilities in the United States have 3-D devices (as of April 2021). That percentage has climbed steadily in recent years. “By the time the TMIST study is completed, DBT will, almost certainly, have become the ‘standard of care,’” he asserts, echoing others who have commented on the trial, including some participating physicians.
The money being spent on TMIST “should not be used for looking backwards,” says Dr. Kopans.
The NCI responded to that criticism. “TMIST is looking to clarify the best screening for women based on the science and is not solely about access. We are seeking to determine which technology is better and [are] providing access to the trial across the country in diverse practices and populations,” the NCI said in an email.
In his essay, Dr. Kopans says it is time to stop TMIST and put the money into other pressing breast cancer issues and questions. “... it makes no sense to continue this flawed trial whose results will be obsolete by the time they become available,” he writes.
Dr. Kopans reports consulting with DART Imaging in China, which is developing a digital breast tomosynthesis machine.
A version of this article first appeared on Medscape.com.
Funding for this trial is largely misspent money, it may produce misleading results, and it should be abandoned, he says.
Dr. Kopans has been an outspoken critic of the trial, describing it as a “huge waste of money” in comments made last year. Now he has set out his criticisms of the trial in an essay published in the October issue of Clinical Imaging, which outlines his objections and concerns for the first time in a peer-reviewed journal.
The Tomosynthesis Mammographic Imaging Screening Trial (TMIST) is comparing digital breast tomosynthesis (DBT), also known as 3-D mammography, with the older 2-D technology or full-field digital mammography (FFDM).
Dr. Kopans coined the term DBT and formerly held a now-expired patent on the first version of this technology.
“It could be argued that the imaging part of TMIST is a waste of valuable resources,” he writes in the essay.
The “imaging part” of the trial refers to the primary outcome measure and driving purpose of the trial, which is designed to learn which technology is better at finding – and reducing the rate of – potentially lethal “advanced” cancers.
These cancers include larger HER2-positive and triple-negative malignancies; those associated with positive nodes; and metastatic disease. These malignancies correlate with breast cancer mortality, TMIST’s principal investigator Etta Pisano, MD, of the American College of Radiology, has said in the past.
However, Dr. Kopans says that this surrogate endpoint is problematic. “TMIST will only investigate whether or not digital breast tomography results in a decline in advanced cancers, ignoring the fact that many women still die from cancers that are not advanced at the time of diagnosis,” he writes.
“Clearly reducing the rate of advanced cancers is not the only way that early detection saves lives. Lives are also saved by finding cancers at a smaller size within stages,” Dr. Kopans writes. He adds that DBT has been proven in observational cohort studies to find more smaller breast cancers than FFDM.
Dr. Kopans’ opinion that TMIST is largely a waste of resources is not shared by the National Cancer Institute. “We feel strongly that TMIST is a critical study,” an NCI spokesperson told this news organization.
Study power concerns
Another concern is that TMIST “may be underpowered,” Dr. Kopans writes. That concern arises in part from a recent review of TMIST by an advisory committee (that was prompted by low patient accrual rates), which proposed reducing the size of the trial. Dr. Kopans says this would result in “a reduction of the planned power of the trial.”
The NCI says that reducing the study size has been discussed but has not yet been implemented. “Any reduction in size would, of course, have appropriate statistical considerations in mind,” according to the NCI spokesperson.
Dr. Kopans’ concern about statistical power extends beyond downsizing the trial. An advanced cancer in TMIST is counted “if it occurs at any time while the participant is on study,” according to the NCI. Dr. Kopans says that is a problem.
“Since DBT cannot have any effect on advanced cancers in the prevalence year (they are already there), data from the first year (prevalence cancers are likely the largest number) will be unusable, and if used will, inappropriately, dilute the results,” he writes.
Dr. Kopans hopes that the investigators address the statistical power issues with the trial because, if not, “its results may be grossly misleading.”
American radiology practice
Dr. Kopans praises one aspect of TMIST – the trial’s effort to create a repository of blood and oral swab specimens, along with participant genetic data. The goal, say TMIST investigators, is to individualize or optimize screening strategies by tying molecular data to clinical outcomes in the trial.
However, apart from that one aspect, Dr. Kopans is highly critical of the trial.
It is now too late to compare the two technologies, he suggests, as DBT is already replacing FFDM for breast cancer screening in the U.S.
He notes that 76% of mammography facilities in the United States have 3-D devices (as of April 2021). That percentage has climbed steadily in recent years. “By the time the TMIST study is completed, DBT will, almost certainly, have become the ‘standard of care,’” he asserts, echoing others who have commented on the trial, including some participating physicians.
The money being spent on TMIST “should not be used for looking backwards,” says Dr. Kopans.
The NCI responded to that criticism. “TMIST is looking to clarify the best screening for women based on the science and is not solely about access. We are seeking to determine which technology is better and [are] providing access to the trial across the country in diverse practices and populations,” the NCI said in an email.
In his essay, Dr. Kopans says it is time to stop TMIST and put the money into other pressing breast cancer issues and questions. “... it makes no sense to continue this flawed trial whose results will be obsolete by the time they become available,” he writes.
Dr. Kopans reports consulting with DART Imaging in China, which is developing a digital breast tomosynthesis machine.
A version of this article first appeared on Medscape.com.
Funding for this trial is largely misspent money, it may produce misleading results, and it should be abandoned, he says.
Dr. Kopans has been an outspoken critic of the trial, describing it as a “huge waste of money” in comments made last year. Now he has set out his criticisms of the trial in an essay published in the October issue of Clinical Imaging, which outlines his objections and concerns for the first time in a peer-reviewed journal.
The Tomosynthesis Mammographic Imaging Screening Trial (TMIST) is comparing digital breast tomosynthesis (DBT), also known as 3-D mammography, with the older 2-D technology or full-field digital mammography (FFDM).
Dr. Kopans coined the term DBT and formerly held a now-expired patent on the first version of this technology.
“It could be argued that the imaging part of TMIST is a waste of valuable resources,” he writes in the essay.
The “imaging part” of the trial refers to the primary outcome measure and driving purpose of the trial, which is designed to learn which technology is better at finding – and reducing the rate of – potentially lethal “advanced” cancers.
These cancers include larger HER2-positive and triple-negative malignancies; those associated with positive nodes; and metastatic disease. These malignancies correlate with breast cancer mortality, TMIST’s principal investigator Etta Pisano, MD, of the American College of Radiology, has said in the past.
However, Dr. Kopans says that this surrogate endpoint is problematic. “TMIST will only investigate whether or not digital breast tomography results in a decline in advanced cancers, ignoring the fact that many women still die from cancers that are not advanced at the time of diagnosis,” he writes.
“Clearly reducing the rate of advanced cancers is not the only way that early detection saves lives. Lives are also saved by finding cancers at a smaller size within stages,” Dr. Kopans writes. He adds that DBT has been proven in observational cohort studies to find more smaller breast cancers than FFDM.
Dr. Kopans’ opinion that TMIST is largely a waste of resources is not shared by the National Cancer Institute. “We feel strongly that TMIST is a critical study,” an NCI spokesperson told this news organization.
Study power concerns
Another concern is that TMIST “may be underpowered,” Dr. Kopans writes. That concern arises in part from a recent review of TMIST by an advisory committee (that was prompted by low patient accrual rates), which proposed reducing the size of the trial. Dr. Kopans says this would result in “a reduction of the planned power of the trial.”
The NCI says that reducing the study size has been discussed but has not yet been implemented. “Any reduction in size would, of course, have appropriate statistical considerations in mind,” according to the NCI spokesperson.
Dr. Kopans’ concern about statistical power extends beyond downsizing the trial. An advanced cancer in TMIST is counted “if it occurs at any time while the participant is on study,” according to the NCI. Dr. Kopans says that is a problem.
“Since DBT cannot have any effect on advanced cancers in the prevalence year (they are already there), data from the first year (prevalence cancers are likely the largest number) will be unusable, and if used will, inappropriately, dilute the results,” he writes.
Dr. Kopans hopes that the investigators address the statistical power issues with the trial because, if not, “its results may be grossly misleading.”
American radiology practice
Dr. Kopans praises one aspect of TMIST – the trial’s effort to create a repository of blood and oral swab specimens, along with participant genetic data. The goal, say TMIST investigators, is to individualize or optimize screening strategies by tying molecular data to clinical outcomes in the trial.
However, apart from that one aspect, Dr. Kopans is highly critical of the trial.
It is now too late to compare the two technologies, he suggests, as DBT is already replacing FFDM for breast cancer screening in the U.S.
He notes that 76% of mammography facilities in the United States have 3-D devices (as of April 2021). That percentage has climbed steadily in recent years. “By the time the TMIST study is completed, DBT will, almost certainly, have become the ‘standard of care,’” he asserts, echoing others who have commented on the trial, including some participating physicians.
The money being spent on TMIST “should not be used for looking backwards,” says Dr. Kopans.
The NCI responded to that criticism. “TMIST is looking to clarify the best screening for women based on the science and is not solely about access. We are seeking to determine which technology is better and [are] providing access to the trial across the country in diverse practices and populations,” the NCI said in an email.
In his essay, Dr. Kopans says it is time to stop TMIST and put the money into other pressing breast cancer issues and questions. “... it makes no sense to continue this flawed trial whose results will be obsolete by the time they become available,” he writes.
Dr. Kopans reports consulting with DART Imaging in China, which is developing a digital breast tomosynthesis machine.
A version of this article first appeared on Medscape.com.
Does eating nuts lead to better breast cancer outcomes?
In the first study of its kind, , compared with those who said they had not eaten nuts.
There was also an improvement in overall survival, but this was not statistically significant.
The finding comes from a study of more than 3,000 patients conducted in China, published online in the International Journal of Cancer. Patients were queried about nut consumption on only one occasion, 5 years after their breast cancer diagnosis.
The investigators report a dose-response pattern between nut eating and the risk of both breast cancer recurrence and overall mortality, with those consuming the largest amounts having the lowest risks.
“Nuts are important components of healthy diets. Promoting this modifiable lifestyle factor should be emphasized in breast cancer survivor guidelines,” conclude Xiao-Ou Shu, MD, PhD, of Vanderbilt University, Nashville, Tenn., and colleagues in the study.
“The association for disease-free survival is quite strong and robust,” Dr. Shu told this news organization.
However, as with all observational studies, this report shows an association and not causation.
“Based upon this study alone, the evidence is weak,” said Wendy Chen, MD, MPH, a breast oncologist at Dana-Farber Cancer Institute in Boston, who was approached for comment.
The people who consumed nuts generally had more education, higher income, lower body mass index, earlier-stage cancers, and more physically active lives – all factors associated with better breast cancer survival, she observed. “The authors tried to control for these factors,” Dr. Chen acknowledged. But it’s hard to know whether nut consumption was “truly” the difference maker, she said.
Furthermore, the study population is also “a bit unusual” because people had to survive 5 years after diagnosis to be included in the analysis – and thus is not representative of breast cancer survivors, she noted.
Erin Van Blarigan, PhD, an epidemiologist at the University of California, San Francisco, described the overall evidence of the beneficial relationship between nut eating and breast cancer – including this study – as “limited.” She previously led a study that observed benefits of nut intake for patients with colon cancer.
Dr. Van Blarigan also noted that nut intake in this study was “very low” – with the median intake less than one serving per week.
She also offered some general advice about eating nuts.
“Nuts are an energy-dense food, so portion sizes should be kept small,” she said, explaining a portion should be about 1 ounce or 1/4 cup of nuts or 1-2 tablespoons of nut butter.
A little may go a long way, she suggested, as research to date “suggests only small amounts may be needed to gain potential benefits.”
The level of nut consumption was low in the Chinese study population (median = 17.3 grams/week) compared with the 42.5 grams/week recommended by the American Heart Association, the study authors acknowledge.
“Nuts, particularly tree nuts, are expensive in China. Traditionally, nut consumption level has been low among Chinese, particularly in the old generation,” commented Dr. Shu.
Study authors did an adjusted analysis
The new study was conducted among 3,449 participants of the Shanghai Breast Cancer Survival Study.
Nut consumption (including peanuts and tree nuts such as walnuts) was assessed with a food questionnaire at 5 years post-diagnosis.
An analysis was conducted at 10 years post-diagnosis (and 5 years after the diet questionnaire). At this 10-year mark, there were 252 breast cancer-specific deaths. Among 3,274 survivors without previous recurrence at the dietary assessment, 209 went on to develop breast cancer-specific events – either recurrence, metastasis, or breast cancer mortality.
Nut consumers had higher overall survival (93.7% vs. 89%; P = .003) and disease-free survival (94.1% vs. 86.2%; P <.001) rates than nonconsumers.
However, the two groups had many differences, as noted by the authors and outside experts.
The consumers had a younger age at diagnosis, lower BMI, higher total energy intake, higher diet quality score, and higher soy food intake. In addition, nut consumers were more likely to have a higher education, personal income, and physical activity level (≥7.5 metabolic equivalent of task-hour/week) as well as to have received immunotherapy.
So the investigators adjusted for many of those variables and found that nut consumption was associated with significantly better disease-free survival (hazard ratio, 0.52; 95% confidence interval, 0.35-0.75), but a nonsignificantly improved overall survival (HR, 0.90; 95% CI, 0.66-1.23), as noted above.
Analyses by amount of nut intake showed a dose-response relationship for both overall survival (P trend = .022) and disease-free survival (P trend = .003).
The authors say that “there has been no strong evidence to support individual food items in favor of breast cancer survival,” citing a 2018 report entitled “Diet, Nutrition, Physical Activity and Breast Cancer Survivors” from the World Cancer Research Fund/American Institute for Cancer Research.
The new study provides evidence that nuts may be such a food, they say, while also calling for studies to confirm their findings.
Study limitations include that fact that the statuses of recurrence and metastasis were self-reported. Misclassification, particularly regarding the event date, is likely, the team says.
The study authors and Dr. Van Blarigan and Dr. Chen have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In the first study of its kind, , compared with those who said they had not eaten nuts.
There was also an improvement in overall survival, but this was not statistically significant.
The finding comes from a study of more than 3,000 patients conducted in China, published online in the International Journal of Cancer. Patients were queried about nut consumption on only one occasion, 5 years after their breast cancer diagnosis.
The investigators report a dose-response pattern between nut eating and the risk of both breast cancer recurrence and overall mortality, with those consuming the largest amounts having the lowest risks.
“Nuts are important components of healthy diets. Promoting this modifiable lifestyle factor should be emphasized in breast cancer survivor guidelines,” conclude Xiao-Ou Shu, MD, PhD, of Vanderbilt University, Nashville, Tenn., and colleagues in the study.
“The association for disease-free survival is quite strong and robust,” Dr. Shu told this news organization.
However, as with all observational studies, this report shows an association and not causation.
“Based upon this study alone, the evidence is weak,” said Wendy Chen, MD, MPH, a breast oncologist at Dana-Farber Cancer Institute in Boston, who was approached for comment.
The people who consumed nuts generally had more education, higher income, lower body mass index, earlier-stage cancers, and more physically active lives – all factors associated with better breast cancer survival, she observed. “The authors tried to control for these factors,” Dr. Chen acknowledged. But it’s hard to know whether nut consumption was “truly” the difference maker, she said.
Furthermore, the study population is also “a bit unusual” because people had to survive 5 years after diagnosis to be included in the analysis – and thus is not representative of breast cancer survivors, she noted.
Erin Van Blarigan, PhD, an epidemiologist at the University of California, San Francisco, described the overall evidence of the beneficial relationship between nut eating and breast cancer – including this study – as “limited.” She previously led a study that observed benefits of nut intake for patients with colon cancer.
Dr. Van Blarigan also noted that nut intake in this study was “very low” – with the median intake less than one serving per week.
She also offered some general advice about eating nuts.
“Nuts are an energy-dense food, so portion sizes should be kept small,” she said, explaining a portion should be about 1 ounce or 1/4 cup of nuts or 1-2 tablespoons of nut butter.
A little may go a long way, she suggested, as research to date “suggests only small amounts may be needed to gain potential benefits.”
The level of nut consumption was low in the Chinese study population (median = 17.3 grams/week) compared with the 42.5 grams/week recommended by the American Heart Association, the study authors acknowledge.
“Nuts, particularly tree nuts, are expensive in China. Traditionally, nut consumption level has been low among Chinese, particularly in the old generation,” commented Dr. Shu.
Study authors did an adjusted analysis
The new study was conducted among 3,449 participants of the Shanghai Breast Cancer Survival Study.
Nut consumption (including peanuts and tree nuts such as walnuts) was assessed with a food questionnaire at 5 years post-diagnosis.
An analysis was conducted at 10 years post-diagnosis (and 5 years after the diet questionnaire). At this 10-year mark, there were 252 breast cancer-specific deaths. Among 3,274 survivors without previous recurrence at the dietary assessment, 209 went on to develop breast cancer-specific events – either recurrence, metastasis, or breast cancer mortality.
Nut consumers had higher overall survival (93.7% vs. 89%; P = .003) and disease-free survival (94.1% vs. 86.2%; P <.001) rates than nonconsumers.
However, the two groups had many differences, as noted by the authors and outside experts.
The consumers had a younger age at diagnosis, lower BMI, higher total energy intake, higher diet quality score, and higher soy food intake. In addition, nut consumers were more likely to have a higher education, personal income, and physical activity level (≥7.5 metabolic equivalent of task-hour/week) as well as to have received immunotherapy.
So the investigators adjusted for many of those variables and found that nut consumption was associated with significantly better disease-free survival (hazard ratio, 0.52; 95% confidence interval, 0.35-0.75), but a nonsignificantly improved overall survival (HR, 0.90; 95% CI, 0.66-1.23), as noted above.
Analyses by amount of nut intake showed a dose-response relationship for both overall survival (P trend = .022) and disease-free survival (P trend = .003).
The authors say that “there has been no strong evidence to support individual food items in favor of breast cancer survival,” citing a 2018 report entitled “Diet, Nutrition, Physical Activity and Breast Cancer Survivors” from the World Cancer Research Fund/American Institute for Cancer Research.
The new study provides evidence that nuts may be such a food, they say, while also calling for studies to confirm their findings.
Study limitations include that fact that the statuses of recurrence and metastasis were self-reported. Misclassification, particularly regarding the event date, is likely, the team says.
The study authors and Dr. Van Blarigan and Dr. Chen have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In the first study of its kind, , compared with those who said they had not eaten nuts.
There was also an improvement in overall survival, but this was not statistically significant.
The finding comes from a study of more than 3,000 patients conducted in China, published online in the International Journal of Cancer. Patients were queried about nut consumption on only one occasion, 5 years after their breast cancer diagnosis.
The investigators report a dose-response pattern between nut eating and the risk of both breast cancer recurrence and overall mortality, with those consuming the largest amounts having the lowest risks.
“Nuts are important components of healthy diets. Promoting this modifiable lifestyle factor should be emphasized in breast cancer survivor guidelines,” conclude Xiao-Ou Shu, MD, PhD, of Vanderbilt University, Nashville, Tenn., and colleagues in the study.
“The association for disease-free survival is quite strong and robust,” Dr. Shu told this news organization.
However, as with all observational studies, this report shows an association and not causation.
“Based upon this study alone, the evidence is weak,” said Wendy Chen, MD, MPH, a breast oncologist at Dana-Farber Cancer Institute in Boston, who was approached for comment.
The people who consumed nuts generally had more education, higher income, lower body mass index, earlier-stage cancers, and more physically active lives – all factors associated with better breast cancer survival, she observed. “The authors tried to control for these factors,” Dr. Chen acknowledged. But it’s hard to know whether nut consumption was “truly” the difference maker, she said.
Furthermore, the study population is also “a bit unusual” because people had to survive 5 years after diagnosis to be included in the analysis – and thus is not representative of breast cancer survivors, she noted.
Erin Van Blarigan, PhD, an epidemiologist at the University of California, San Francisco, described the overall evidence of the beneficial relationship between nut eating and breast cancer – including this study – as “limited.” She previously led a study that observed benefits of nut intake for patients with colon cancer.
Dr. Van Blarigan also noted that nut intake in this study was “very low” – with the median intake less than one serving per week.
She also offered some general advice about eating nuts.
“Nuts are an energy-dense food, so portion sizes should be kept small,” she said, explaining a portion should be about 1 ounce or 1/4 cup of nuts or 1-2 tablespoons of nut butter.
A little may go a long way, she suggested, as research to date “suggests only small amounts may be needed to gain potential benefits.”
The level of nut consumption was low in the Chinese study population (median = 17.3 grams/week) compared with the 42.5 grams/week recommended by the American Heart Association, the study authors acknowledge.
“Nuts, particularly tree nuts, are expensive in China. Traditionally, nut consumption level has been low among Chinese, particularly in the old generation,” commented Dr. Shu.
Study authors did an adjusted analysis
The new study was conducted among 3,449 participants of the Shanghai Breast Cancer Survival Study.
Nut consumption (including peanuts and tree nuts such as walnuts) was assessed with a food questionnaire at 5 years post-diagnosis.
An analysis was conducted at 10 years post-diagnosis (and 5 years after the diet questionnaire). At this 10-year mark, there were 252 breast cancer-specific deaths. Among 3,274 survivors without previous recurrence at the dietary assessment, 209 went on to develop breast cancer-specific events – either recurrence, metastasis, or breast cancer mortality.
Nut consumers had higher overall survival (93.7% vs. 89%; P = .003) and disease-free survival (94.1% vs. 86.2%; P <.001) rates than nonconsumers.
However, the two groups had many differences, as noted by the authors and outside experts.
The consumers had a younger age at diagnosis, lower BMI, higher total energy intake, higher diet quality score, and higher soy food intake. In addition, nut consumers were more likely to have a higher education, personal income, and physical activity level (≥7.5 metabolic equivalent of task-hour/week) as well as to have received immunotherapy.
So the investigators adjusted for many of those variables and found that nut consumption was associated with significantly better disease-free survival (hazard ratio, 0.52; 95% confidence interval, 0.35-0.75), but a nonsignificantly improved overall survival (HR, 0.90; 95% CI, 0.66-1.23), as noted above.
Analyses by amount of nut intake showed a dose-response relationship for both overall survival (P trend = .022) and disease-free survival (P trend = .003).
The authors say that “there has been no strong evidence to support individual food items in favor of breast cancer survival,” citing a 2018 report entitled “Diet, Nutrition, Physical Activity and Breast Cancer Survivors” from the World Cancer Research Fund/American Institute for Cancer Research.
The new study provides evidence that nuts may be such a food, they say, while also calling for studies to confirm their findings.
Study limitations include that fact that the statuses of recurrence and metastasis were self-reported. Misclassification, particularly regarding the event date, is likely, the team says.
The study authors and Dr. Van Blarigan and Dr. Chen have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FDA approves first CAR T-cell for adult ALL: For patients with R/R B-cell disease
The therapy is the first chimeric antigen receptor (CAR) T-cell treatment approved for adults with ALL.
This is a “meaningful advance,” because “roughly half of all adults with B-ALL will relapse on currently available therapies,” said Bijal Shah, MD, of Moffitt Cancer Center, Tampa, Fla., in a press statement from the manufacturer, Kite.
“A single infusion of Tecartus has demonstrated durable responses, suggesting the potential for long-term remission and a new approach to care,” he added.
“Roughly half of all cases actually occur in adults, and unlike pediatric ALL, adult ALL has historically had a poor prognosis,” said Lee Greenberger, PhD, chief scientific officer at the Leukemia & Lymphoma Society, in the statement. The median overall survival (OS) is only about 8 months in this setting with current treatments, according to the company.
The new FDA approval, which is the fourth indication for brexucabtagene autoleucel, is based on results from ZUMA-3, a multicenter, single-arm study of 71 patients, with 54 efficacy-evaluable patients.
Efficacy was established on the basis of complete remission (CR) rate within 3 months after infusion and the duration of CR (DOCR). Twenty-eight (51.9%) of evaluable patients achieved CR, with a median follow-up for responders of 7.1 months. The median DOCR was not reached.
The median time to CR was 56 days. All 54 efficacy-evaluable patients had potential follow-up for 10 or more months with a median actual follow-up time of 12.3 months.
Among the 54 patients, the median time from leukapheresis to product delivery was 16 days and the median time from leukapheresis to infusion was 29 days.
Of the 17 study patients who did reach efficacy evaluation, 6 did not receive the agent because of manufacturing failure, 8 were not treated because of adverse events following leukapheresis, 2 underwent leukapheresis and received lymphodepleting chemotherapy but were not treated with the drug, and 1 treated patient was not evaluable for efficacy, per the prescribing information.
Among all patients treated with brexucabtagene autoleucel at its target dose, grade 3 or higher cytokine release syndrome (CRS) and neurologic events occurred in 26% and 35% of patients, respectively, and were generally well managed, according to the company.
The most common adverse reactions (≥20%) among ALL patients are fever, CRS, hypotension, encephalopathy, tachycardia, nausea, chills, headache, fatigue, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with pathogen unspecified, constipation, decreased appetite, and vomiting.
The prescribing information includes a boxed warning about the risks of CRS and neurologic toxicities; the drug is approved with a Risk Evaluation and Mitigation Strategy (REMS) because of these risks.
A version of this article first appeared on Medscape.com.
The therapy is the first chimeric antigen receptor (CAR) T-cell treatment approved for adults with ALL.
This is a “meaningful advance,” because “roughly half of all adults with B-ALL will relapse on currently available therapies,” said Bijal Shah, MD, of Moffitt Cancer Center, Tampa, Fla., in a press statement from the manufacturer, Kite.
“A single infusion of Tecartus has demonstrated durable responses, suggesting the potential for long-term remission and a new approach to care,” he added.
“Roughly half of all cases actually occur in adults, and unlike pediatric ALL, adult ALL has historically had a poor prognosis,” said Lee Greenberger, PhD, chief scientific officer at the Leukemia & Lymphoma Society, in the statement. The median overall survival (OS) is only about 8 months in this setting with current treatments, according to the company.
The new FDA approval, which is the fourth indication for brexucabtagene autoleucel, is based on results from ZUMA-3, a multicenter, single-arm study of 71 patients, with 54 efficacy-evaluable patients.
Efficacy was established on the basis of complete remission (CR) rate within 3 months after infusion and the duration of CR (DOCR). Twenty-eight (51.9%) of evaluable patients achieved CR, with a median follow-up for responders of 7.1 months. The median DOCR was not reached.
The median time to CR was 56 days. All 54 efficacy-evaluable patients had potential follow-up for 10 or more months with a median actual follow-up time of 12.3 months.
Among the 54 patients, the median time from leukapheresis to product delivery was 16 days and the median time from leukapheresis to infusion was 29 days.
Of the 17 study patients who did reach efficacy evaluation, 6 did not receive the agent because of manufacturing failure, 8 were not treated because of adverse events following leukapheresis, 2 underwent leukapheresis and received lymphodepleting chemotherapy but were not treated with the drug, and 1 treated patient was not evaluable for efficacy, per the prescribing information.
Among all patients treated with brexucabtagene autoleucel at its target dose, grade 3 or higher cytokine release syndrome (CRS) and neurologic events occurred in 26% and 35% of patients, respectively, and were generally well managed, according to the company.
The most common adverse reactions (≥20%) among ALL patients are fever, CRS, hypotension, encephalopathy, tachycardia, nausea, chills, headache, fatigue, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with pathogen unspecified, constipation, decreased appetite, and vomiting.
The prescribing information includes a boxed warning about the risks of CRS and neurologic toxicities; the drug is approved with a Risk Evaluation and Mitigation Strategy (REMS) because of these risks.
A version of this article first appeared on Medscape.com.
The therapy is the first chimeric antigen receptor (CAR) T-cell treatment approved for adults with ALL.
This is a “meaningful advance,” because “roughly half of all adults with B-ALL will relapse on currently available therapies,” said Bijal Shah, MD, of Moffitt Cancer Center, Tampa, Fla., in a press statement from the manufacturer, Kite.
“A single infusion of Tecartus has demonstrated durable responses, suggesting the potential for long-term remission and a new approach to care,” he added.
“Roughly half of all cases actually occur in adults, and unlike pediatric ALL, adult ALL has historically had a poor prognosis,” said Lee Greenberger, PhD, chief scientific officer at the Leukemia & Lymphoma Society, in the statement. The median overall survival (OS) is only about 8 months in this setting with current treatments, according to the company.
The new FDA approval, which is the fourth indication for brexucabtagene autoleucel, is based on results from ZUMA-3, a multicenter, single-arm study of 71 patients, with 54 efficacy-evaluable patients.
Efficacy was established on the basis of complete remission (CR) rate within 3 months after infusion and the duration of CR (DOCR). Twenty-eight (51.9%) of evaluable patients achieved CR, with a median follow-up for responders of 7.1 months. The median DOCR was not reached.
The median time to CR was 56 days. All 54 efficacy-evaluable patients had potential follow-up for 10 or more months with a median actual follow-up time of 12.3 months.
Among the 54 patients, the median time from leukapheresis to product delivery was 16 days and the median time from leukapheresis to infusion was 29 days.
Of the 17 study patients who did reach efficacy evaluation, 6 did not receive the agent because of manufacturing failure, 8 were not treated because of adverse events following leukapheresis, 2 underwent leukapheresis and received lymphodepleting chemotherapy but were not treated with the drug, and 1 treated patient was not evaluable for efficacy, per the prescribing information.
Among all patients treated with brexucabtagene autoleucel at its target dose, grade 3 or higher cytokine release syndrome (CRS) and neurologic events occurred in 26% and 35% of patients, respectively, and were generally well managed, according to the company.
The most common adverse reactions (≥20%) among ALL patients are fever, CRS, hypotension, encephalopathy, tachycardia, nausea, chills, headache, fatigue, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with pathogen unspecified, constipation, decreased appetite, and vomiting.
The prescribing information includes a boxed warning about the risks of CRS and neurologic toxicities; the drug is approved with a Risk Evaluation and Mitigation Strategy (REMS) because of these risks.
A version of this article first appeared on Medscape.com.