Mark L. Fuerst

Universal multigene panel testing of colorectal cancer patients can detect heritable mutations that would not have been discovered with guideline-based testing, according to new research.

A prospective study of universal genetic testing suggested that one in six colorectal cancer patients have an inherited genetic predisposition to the cancer. More than half of the patients with genetic mutations identified in this study would have been missed if the patients had undergone genetic testing based on current practice. In 11% of patients, the genetic findings led to a change in treatment, including the type of surgery or targeted cancer therapy.

These results were presented at the American College of Medical Genetics and Genomics annual meeting and published in Clinical Gastroenterology and Hepatology.

“This study shows the limitations of relying on current clinical practice guidelines for genetic evaluation, which prioritize age of cancer diagnosis and family cancer history,” said investigator Niloy Jewel Samadder, MD, of the Mayo Clinic in Phoenix.

“We were surprised that more than 50% of the patients with a genetic mutation would not have been identified had we relied on national practice guidelines or only used a small colon cancer-specific gene panel, as is commonly employed in clinical practice. The fact that more than 10% of patients actually had changes in the type of surgery or chemo/immunotherapy they received gives the strongest indicator of how genetics can revolutionize and individualize cancer care,” Dr. Samadder said.

He added that identifying a germline predisposition has multiple values, including understanding the reason patients and their family members develop specific cancers, preventing the development of new cancers in patients and family members by providing targeted prevention and screening for those at genetic risk, and improving survival in patients with a genetic driver of cancer via targeted therapy.
 

Study details

The researchers used a next-generation sequencing platform with more than 80 genes in colorectal cancer patients (not selected for age or family history) receiving care at Mayo Clinic Cancer Centers between April 1, 2018, and March 31, 2020.

The study included 361 patients with a median age of 57 years. Pathogenic germline variants were identified in 56 patients (15.5%), including 44 patients with moderate and high penetrance cancer susceptibility genes.

Younger age (under 50 years old) was associated with having a germline mutation, but “more importantly, gender, family cancer history, and stage of cancer were not,” Dr. Samadder said.

“The current clinical guidelines rely heavily on these characteristics to determine who should and should not be referred for genetic testing,” he continued. “Our study suggests that even older patients with colorectal cancer have a high rate of having pathogenic germline mutations [12%], so restricting genetic testing to only those under age 50 will miss a substantial portion of patients who might benefit from this test.”
 

Genetic testing for all

“Our findings support the broad use of genetic testing in all colorectal cancer patients, regardless of age, gender, ethnicity, family cancer history, or stage of cancer,” Dr. Samadder said.

“This study adds to a growing body of literature that provides evidence that cancer susceptibility due to variants in single genes is more common than previously appreciated,” said Marc S. Williams, MD, president of the American College of Medical Genetics and Genomics. “Current testing guidelines seem to be relatively insensitive and miss opportunities for testing of patients.”

Dr. Williams noted that 11% of patients in this study had a change in disease management related to a genetic testing result, which is “a relatively modest impact.”

“Another potential advantage of [universal] testing was the opportunity to test at-risk relatives,” Dr. Williams added. “However, only 16% of eligible individuals pursued testing. This is consistent with other studies and represents an opportunity for testing new ways to improve uptake of cascade screening.”

Dr. Williams said rigorous prospective studies enrolling large numbers of patients from diverse backgrounds are needed to inform the development and updating of genetic testing guidelines.

He disclosed no conflicts of interest. Dr. Samadder disclosed relationships with Janssen Research and Development, Recursion Pharmaceuticals, and Cancer Prevention Pharmaceuticals. The research was funded by the Mayo Clinic, Desert Mountain Members’ CARE Foundation, David and Twila Woods Foundation, and the Gerstner Foundation.

Universal multigene panel testing of colorectal cancer patients can detect heritable mutations that would not have been discovered with guideline-based testing, according to new research.

A prospective study of universal genetic testing suggested that one in six colorectal cancer patients have an inherited genetic predisposition to the cancer. More than half of the patients with genetic mutations identified in this study would have been missed if the patients had undergone genetic testing based on current practice. In 11% of patients, the genetic findings led to a change in treatment, including the type of surgery or targeted cancer therapy.

These results were presented at the American College of Medical Genetics and Genomics annual meeting and published in Clinical Gastroenterology and Hepatology.

“This study shows the limitations of relying on current clinical practice guidelines for genetic evaluation, which prioritize age of cancer diagnosis and family cancer history,” said investigator Niloy Jewel Samadder, MD, of the Mayo Clinic in Phoenix.

“We were surprised that more than 50% of the patients with a genetic mutation would not have been identified had we relied on national practice guidelines or only used a small colon cancer-specific gene panel, as is commonly employed in clinical practice. The fact that more than 10% of patients actually had changes in the type of surgery or chemo/immunotherapy they received gives the strongest indicator of how genetics can revolutionize and individualize cancer care,” Dr. Samadder said.

He added that identifying a germline predisposition has multiple values, including understanding the reason patients and their family members develop specific cancers, preventing the development of new cancers in patients and family members by providing targeted prevention and screening for those at genetic risk, and improving survival in patients with a genetic driver of cancer via targeted therapy.
 

Study details

The researchers used a next-generation sequencing platform with more than 80 genes in colorectal cancer patients (not selected for age or family history) receiving care at Mayo Clinic Cancer Centers between April 1, 2018, and March 31, 2020.

The study included 361 patients with a median age of 57 years. Pathogenic germline variants were identified in 56 patients (15.5%), including 44 patients with moderate and high penetrance cancer susceptibility genes.

Younger age (under 50 years old) was associated with having a germline mutation, but “more importantly, gender, family cancer history, and stage of cancer were not,” Dr. Samadder said.

“The current clinical guidelines rely heavily on these characteristics to determine who should and should not be referred for genetic testing,” he continued. “Our study suggests that even older patients with colorectal cancer have a high rate of having pathogenic germline mutations [12%], so restricting genetic testing to only those under age 50 will miss a substantial portion of patients who might benefit from this test.”
 

Genetic testing for all

“Our findings support the broad use of genetic testing in all colorectal cancer patients, regardless of age, gender, ethnicity, family cancer history, or stage of cancer,” Dr. Samadder said.

“This study adds to a growing body of literature that provides evidence that cancer susceptibility due to variants in single genes is more common than previously appreciated,” said Marc S. Williams, MD, president of the American College of Medical Genetics and Genomics. “Current testing guidelines seem to be relatively insensitive and miss opportunities for testing of patients.”

Dr. Williams noted that 11% of patients in this study had a change in disease management related to a genetic testing result, which is “a relatively modest impact.”

“Another potential advantage of [universal] testing was the opportunity to test at-risk relatives,” Dr. Williams added. “However, only 16% of eligible individuals pursued testing. This is consistent with other studies and represents an opportunity for testing new ways to improve uptake of cascade screening.”

Dr. Williams said rigorous prospective studies enrolling large numbers of patients from diverse backgrounds are needed to inform the development and updating of genetic testing guidelines.

He disclosed no conflicts of interest. Dr. Samadder disclosed relationships with Janssen Research and Development, Recursion Pharmaceuticals, and Cancer Prevention Pharmaceuticals. The research was funded by the Mayo Clinic, Desert Mountain Members’ CARE Foundation, David and Twila Woods Foundation, and the Gerstner Foundation.

Universal multigene panel testing of colorectal cancer patients can detect heritable mutations that would not have been discovered with guideline-based testing, according to new research.

A prospective study of universal genetic testing suggested that one in six colorectal cancer patients have an inherited genetic predisposition to the cancer. More than half of the patients with genetic mutations identified in this study would have been missed if the patients had undergone genetic testing based on current practice. In 11% of patients, the genetic findings led to a change in treatment, including the type of surgery or targeted cancer therapy.

These results were presented at the American College of Medical Genetics and Genomics annual meeting and published in Clinical Gastroenterology and Hepatology.

“This study shows the limitations of relying on current clinical practice guidelines for genetic evaluation, which prioritize age of cancer diagnosis and family cancer history,” said investigator Niloy Jewel Samadder, MD, of the Mayo Clinic in Phoenix.

“We were surprised that more than 50% of the patients with a genetic mutation would not have been identified had we relied on national practice guidelines or only used a small colon cancer-specific gene panel, as is commonly employed in clinical practice. The fact that more than 10% of patients actually had changes in the type of surgery or chemo/immunotherapy they received gives the strongest indicator of how genetics can revolutionize and individualize cancer care,” Dr. Samadder said.

He added that identifying a germline predisposition has multiple values, including understanding the reason patients and their family members develop specific cancers, preventing the development of new cancers in patients and family members by providing targeted prevention and screening for those at genetic risk, and improving survival in patients with a genetic driver of cancer via targeted therapy.
 

Study details

The researchers used a next-generation sequencing platform with more than 80 genes in colorectal cancer patients (not selected for age or family history) receiving care at Mayo Clinic Cancer Centers between April 1, 2018, and March 31, 2020.

The study included 361 patients with a median age of 57 years. Pathogenic germline variants were identified in 56 patients (15.5%), including 44 patients with moderate and high penetrance cancer susceptibility genes.

Younger age (under 50 years old) was associated with having a germline mutation, but “more importantly, gender, family cancer history, and stage of cancer were not,” Dr. Samadder said.

“The current clinical guidelines rely heavily on these characteristics to determine who should and should not be referred for genetic testing,” he continued. “Our study suggests that even older patients with colorectal cancer have a high rate of having pathogenic germline mutations [12%], so restricting genetic testing to only those under age 50 will miss a substantial portion of patients who might benefit from this test.”
 

Genetic testing for all

“Our findings support the broad use of genetic testing in all colorectal cancer patients, regardless of age, gender, ethnicity, family cancer history, or stage of cancer,” Dr. Samadder said.

“This study adds to a growing body of literature that provides evidence that cancer susceptibility due to variants in single genes is more common than previously appreciated,” said Marc S. Williams, MD, president of the American College of Medical Genetics and Genomics. “Current testing guidelines seem to be relatively insensitive and miss opportunities for testing of patients.”

Dr. Williams noted that 11% of patients in this study had a change in disease management related to a genetic testing result, which is “a relatively modest impact.”

“Another potential advantage of [universal] testing was the opportunity to test at-risk relatives,” Dr. Williams added. “However, only 16% of eligible individuals pursued testing. This is consistent with other studies and represents an opportunity for testing new ways to improve uptake of cascade screening.”

Dr. Williams said rigorous prospective studies enrolling large numbers of patients from diverse backgrounds are needed to inform the development and updating of genetic testing guidelines.

He disclosed no conflicts of interest. Dr. Samadder disclosed relationships with Janssen Research and Development, Recursion Pharmaceuticals, and Cancer Prevention Pharmaceuticals. The research was funded by the Mayo Clinic, Desert Mountain Members’ CARE Foundation, David and Twila Woods Foundation, and the Gerstner Foundation.

Single-nucleotide polymorphism (SNP) chips often fail to correctly identify rare variants, a large study suggests.

In fact, SNP chips are “extremely unreliable for genotyping very rare pathogenic variants,” and a positive result for such a variant “is more likely to be wrong than right,” researchers reported in the BMJ.

The authors explained that SNP chips are “DNA microarrays that test genetic variation at many hundreds of thousands of specific locations across the genome.” Although SNP chips have proven accurate in identifying common variants, past reports have suggested that SNP chips perform poorly for genotyping rare variants.

To gain more insight, Caroline Wright, PhD, of the University of Exeter (England) and colleagues conducted a large study.

The researchers analyzed data on 49,908 people from the UK Biobank who had SNP chip and next-generation sequencing results, as well as an additional 21 people who purchased consumer genetic tests and shared their data online via the Personal Genome Project.

The researchers compared the SNP chip and sequencing results. They also selected rare pathogenic variants in BRCA1 and BRCA2 for detailed analysis of clinically actionable variants in the UK Biobank, and they assessed BRCA-related cancers in participants using cancer registry data.
 

Largest evaluation of SNP chips

SNP chips performed well for common variants, the researchers found. Sensitivity, specificity, positive-predictive value, and negative-predictive value all exceeded 99% for 108,574 common variants.

For rare variants, SNP chips performed poorly, with a positive-predictive value of 16% for variants with a frequency below 0.001% in the UK Biobank.

“The study provides the largest evaluation of the performance of SNP chips for genotyping genetic variants at different frequencies in the population, particularly focusing on very rare variants,” Dr. Wright said. “The biggest surprise was how poorly the SNP chips we evaluated performed for rare variants.”

Dr. Wright noted that there is an inherent problem built into using SNP chip technology to genotype very rare variants.

“The SNP chip technology relies on clustering data from multiple individuals in order to determine what genotype each individual has at a specific position in their genome,” Dr. Wright explained. “Although this method works very well for common variants, the rarer the variant, the harder it is to distinguish from experimental noise.”
 

False positives and cancer: ‘Don’t trust the results’

The researchers found that, for rare BRCA variants (frequency below 0.01%), SNP chips had a sensitivity of 34.6%, specificity of 98.3%, negative-predictive value of 99.9%, and positive-predictive value of 4.2%.

Rates of BRCA-related cancers in patients with positive SNP chip results were similar to rates in age-matched control subjects because “the vast majority of variants were false positives,” the researchers noted.

“If these variants are incorrectly genotyped – that is, false positives detected – a woman could be offered screening or even prophylactic surgery inappropriately when she is more likely to be at population background risk [for BRCA-related cancers],” Dr. Wright said.

“For very-rare-disease–causing genetic variants, don’t trust the results from SNP chips; for example, those from direct-to-consumer genetic tests. Never use them to guide clinical action without diagnostic validation,” she added.

Heather Hampel, a genetic counselor and researcher at the Ohio State University Comprehensive Cancer Center in Columbus, agreed.

“Positive results on SNP-based tests need to be confirmed by medical-grade genetic testing using a sequencing technology,” she said. “Negative results on an SNP- based test cannot be considered to rule out mutations in BRCA1/2 or other cancer-susceptibility genes, so individuals with strong personal and family histories of cancer should be seen by a genetic counselor to consider medical-grade genetic testing using a sequencing technology.”

Practicing oncologists can trust patients’ prior germline genetic test results if the testing was performed in a cancer genetics clinic, which uses sequencing-based technologies, Ms. Hampel noted.

“If the test was performed before 2013, there are likely new genes that have been discovered for which their patient was not tested, and repeat testing may be warranted,” Ms. Hampel said. “A referral to a cancer genetic counselor would be appropriate.”

Ms. Hampel disclosed relationships with Genome Medical, GI OnDemand, Invitae Genetics, and Promega. Dr. Wright and her coauthors disclosed no conflicts of interest. The group’s research was conducted using the UK Biobank and the University of Exeter High-Performance Computing, with funding from the Wellcome Trust and the National Institute for Health Research.

Single-nucleotide polymorphism (SNP) chips often fail to correctly identify rare variants, a large study suggests.

In fact, SNP chips are “extremely unreliable for genotyping very rare pathogenic variants,” and a positive result for such a variant “is more likely to be wrong than right,” researchers reported in the BMJ.

The authors explained that SNP chips are “DNA microarrays that test genetic variation at many hundreds of thousands of specific locations across the genome.” Although SNP chips have proven accurate in identifying common variants, past reports have suggested that SNP chips perform poorly for genotyping rare variants.

To gain more insight, Caroline Wright, PhD, of the University of Exeter (England) and colleagues conducted a large study.

The researchers analyzed data on 49,908 people from the UK Biobank who had SNP chip and next-generation sequencing results, as well as an additional 21 people who purchased consumer genetic tests and shared their data online via the Personal Genome Project.

The researchers compared the SNP chip and sequencing results. They also selected rare pathogenic variants in BRCA1 and BRCA2 for detailed analysis of clinically actionable variants in the UK Biobank, and they assessed BRCA-related cancers in participants using cancer registry data.
 

Largest evaluation of SNP chips

SNP chips performed well for common variants, the researchers found. Sensitivity, specificity, positive-predictive value, and negative-predictive value all exceeded 99% for 108,574 common variants.

For rare variants, SNP chips performed poorly, with a positive-predictive value of 16% for variants with a frequency below 0.001% in the UK Biobank.

“The study provides the largest evaluation of the performance of SNP chips for genotyping genetic variants at different frequencies in the population, particularly focusing on very rare variants,” Dr. Wright said. “The biggest surprise was how poorly the SNP chips we evaluated performed for rare variants.”

Dr. Wright noted that there is an inherent problem built into using SNP chip technology to genotype very rare variants.

“The SNP chip technology relies on clustering data from multiple individuals in order to determine what genotype each individual has at a specific position in their genome,” Dr. Wright explained. “Although this method works very well for common variants, the rarer the variant, the harder it is to distinguish from experimental noise.”
 

False positives and cancer: ‘Don’t trust the results’

The researchers found that, for rare BRCA variants (frequency below 0.01%), SNP chips had a sensitivity of 34.6%, specificity of 98.3%, negative-predictive value of 99.9%, and positive-predictive value of 4.2%.

Rates of BRCA-related cancers in patients with positive SNP chip results were similar to rates in age-matched control subjects because “the vast majority of variants were false positives,” the researchers noted.

“If these variants are incorrectly genotyped – that is, false positives detected – a woman could be offered screening or even prophylactic surgery inappropriately when she is more likely to be at population background risk [for BRCA-related cancers],” Dr. Wright said.

“For very-rare-disease–causing genetic variants, don’t trust the results from SNP chips; for example, those from direct-to-consumer genetic tests. Never use them to guide clinical action without diagnostic validation,” she added.

Heather Hampel, a genetic counselor and researcher at the Ohio State University Comprehensive Cancer Center in Columbus, agreed.

“Positive results on SNP-based tests need to be confirmed by medical-grade genetic testing using a sequencing technology,” she said. “Negative results on an SNP- based test cannot be considered to rule out mutations in BRCA1/2 or other cancer-susceptibility genes, so individuals with strong personal and family histories of cancer should be seen by a genetic counselor to consider medical-grade genetic testing using a sequencing technology.”

Practicing oncologists can trust patients’ prior germline genetic test results if the testing was performed in a cancer genetics clinic, which uses sequencing-based technologies, Ms. Hampel noted.

“If the test was performed before 2013, there are likely new genes that have been discovered for which their patient was not tested, and repeat testing may be warranted,” Ms. Hampel said. “A referral to a cancer genetic counselor would be appropriate.”

Ms. Hampel disclosed relationships with Genome Medical, GI OnDemand, Invitae Genetics, and Promega. Dr. Wright and her coauthors disclosed no conflicts of interest. The group’s research was conducted using the UK Biobank and the University of Exeter High-Performance Computing, with funding from the Wellcome Trust and the National Institute for Health Research.

Single-nucleotide polymorphism (SNP) chips often fail to correctly identify rare variants, a large study suggests.

In fact, SNP chips are “extremely unreliable for genotyping very rare pathogenic variants,” and a positive result for such a variant “is more likely to be wrong than right,” researchers reported in the BMJ.

The authors explained that SNP chips are “DNA microarrays that test genetic variation at many hundreds of thousands of specific locations across the genome.” Although SNP chips have proven accurate in identifying common variants, past reports have suggested that SNP chips perform poorly for genotyping rare variants.

To gain more insight, Caroline Wright, PhD, of the University of Exeter (England) and colleagues conducted a large study.

The researchers analyzed data on 49,908 people from the UK Biobank who had SNP chip and next-generation sequencing results, as well as an additional 21 people who purchased consumer genetic tests and shared their data online via the Personal Genome Project.

The researchers compared the SNP chip and sequencing results. They also selected rare pathogenic variants in BRCA1 and BRCA2 for detailed analysis of clinically actionable variants in the UK Biobank, and they assessed BRCA-related cancers in participants using cancer registry data.
 

Largest evaluation of SNP chips

SNP chips performed well for common variants, the researchers found. Sensitivity, specificity, positive-predictive value, and negative-predictive value all exceeded 99% for 108,574 common variants.

For rare variants, SNP chips performed poorly, with a positive-predictive value of 16% for variants with a frequency below 0.001% in the UK Biobank.

“The study provides the largest evaluation of the performance of SNP chips for genotyping genetic variants at different frequencies in the population, particularly focusing on very rare variants,” Dr. Wright said. “The biggest surprise was how poorly the SNP chips we evaluated performed for rare variants.”

Dr. Wright noted that there is an inherent problem built into using SNP chip technology to genotype very rare variants.

“The SNP chip technology relies on clustering data from multiple individuals in order to determine what genotype each individual has at a specific position in their genome,” Dr. Wright explained. “Although this method works very well for common variants, the rarer the variant, the harder it is to distinguish from experimental noise.”
 

False positives and cancer: ‘Don’t trust the results’

The researchers found that, for rare BRCA variants (frequency below 0.01%), SNP chips had a sensitivity of 34.6%, specificity of 98.3%, negative-predictive value of 99.9%, and positive-predictive value of 4.2%.

Rates of BRCA-related cancers in patients with positive SNP chip results were similar to rates in age-matched control subjects because “the vast majority of variants were false positives,” the researchers noted.

“If these variants are incorrectly genotyped – that is, false positives detected – a woman could be offered screening or even prophylactic surgery inappropriately when she is more likely to be at population background risk [for BRCA-related cancers],” Dr. Wright said.

“For very-rare-disease–causing genetic variants, don’t trust the results from SNP chips; for example, those from direct-to-consumer genetic tests. Never use them to guide clinical action without diagnostic validation,” she added.

Heather Hampel, a genetic counselor and researcher at the Ohio State University Comprehensive Cancer Center in Columbus, agreed.

“Positive results on SNP-based tests need to be confirmed by medical-grade genetic testing using a sequencing technology,” she said. “Negative results on an SNP- based test cannot be considered to rule out mutations in BRCA1/2 or other cancer-susceptibility genes, so individuals with strong personal and family histories of cancer should be seen by a genetic counselor to consider medical-grade genetic testing using a sequencing technology.”

Practicing oncologists can trust patients’ prior germline genetic test results if the testing was performed in a cancer genetics clinic, which uses sequencing-based technologies, Ms. Hampel noted.

“If the test was performed before 2013, there are likely new genes that have been discovered for which their patient was not tested, and repeat testing may be warranted,” Ms. Hampel said. “A referral to a cancer genetic counselor would be appropriate.”

Ms. Hampel disclosed relationships with Genome Medical, GI OnDemand, Invitae Genetics, and Promega. Dr. Wright and her coauthors disclosed no conflicts of interest. The group’s research was conducted using the UK Biobank and the University of Exeter High-Performance Computing, with funding from the Wellcome Trust and the National Institute for Health Research.

New evidence-based recommendations provide guidance on when to give radiotherapy and chemotherapy to patients with nasopharyngeal carcinoma.

The guidelines, based on data from more than 100 studies, support offering intensity-modulated radiotherapy to all patients with stage II-IVA nasopharyngeal carcinoma. Recommendations for chemotherapy vary according to disease stage, tumor size, number of nodes, and contraindications.

The guidelines, released jointly by the Chinese Society of Clinical Oncology (CSCO) and the American Society of Clinical Oncology (ASCO), were published in the Journal of Clinical Oncology.

“For practicing oncologists in the United States, who often lack experience treating nasopharyngeal cancer, this guideline provides a useful, succinct summary of available evidence and expert recommendations. Nasopharyngeal cancer can be a technically and medically challenging disease to manage, and a multidisciplinary approach should be strongly encouraged,” said ASCO expert Randall J. Kimple, MD, PhD, of the University of Wisconsin–Madison.

“Much of the data guiding our treatment of these patients comes from endemic regions,” he continued. “How these data apply to patients in the U.S. remains a subject of ongoing study. Patients and providers should be encouraged to seek the opinion of a provider with expertise in the management of nasopharyngeal cancer.”

To compile “best practices” for treating nasopharyngeal carcinoma, the ASCO/CSCO expert panel conducted a literature search that included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2020. The panel identified 108 relevant studies and formulated their guidelines based on the evidence.
 

Recommendations

For all patients with stage II-IVA nasopharyngeal carcinoma, the guidelines recommend intensity-modulated radiation therapy with daily image guidance. The recommended dose is 70 Gy in 33-35 fractions over 7 weeks.

“This has been the standard approach at most institutions that treat a sufficient number of nasopharyngeal cancer patients each year,” Dr. Kimple said.

When adding chemotherapy to radiotherapy, two approaches are recommended. The first is induction chemotherapy followed by chemoradiation, and the second is chemoradiation followed by adjuvant chemotherapy.

“There are divergent opinions regarding the optimal approach in these patients, with slightly stronger data supporting the use of induction chemotherapy,” Dr. Kimple said. “For patients with earlier stage nasopharyngeal cancer (T1-2N1 or T2N0), chemotherapy can be offered, and is more strongly recommended for those with more advanced disease (T2N1, bulky disease, high EBV load).”

For patients receiving concurrent chemotherapy and radiotherapy, the recommended regimen is cisplatin given either weekly (40 mg/m²) or triweekly (100 mg/m²).

“The stated goal is to achieve a cumulative cisplatin dose in excess of 200 mg/m² regardless of the approach taken. Several options were provided for patients with a contraindication to cisplatin,” Dr. Kimple said.

Patients with contraindications can receive nedaplatin (100 mg/m² triweekly), carboplatin (area under curve, 5-6 triweekly), oxaliplatin (70 mg/m² weekly), or fluoropyrimidines (capecitabine, 5-fluorouracil, or tegafur).

For induction, the guidelines recommend platinum-based chemotherapy. Options include gemcitabine plus cisplatin, cisplatin plus 5-fluorouracil, cisplatin plus capecitabine, docetaxel plus cisplatin, and docetaxel plus cisplatin and 5-fluorouracil.

“[T]here is less strong evidence regarding the optimal induction chemotherapy approach for patients with nasopharyngeal cancer. Several possible regimens (doublet or triplet) are offered, with the use of platinum-based regimens being the common theme,” Dr. Kimple said.

For adjuvant chemotherapy, the guidelines recommend cisplatin plus 5-fluorouracil or carboplatin plus 5-fluorouracil.

The guidelines also suggest that clinicians take into account a patient’s other chronic conditions when formulating the treatment and follow-up plan.

“Patients with multiple chronic conditions pose a particular challenge to guideline-based care due to being commonly excluded from clinical trials,” Dr. Kimple said. “Shared decision-making plays a key role in the recommendations for patients with multiple chronic conditions. In addition, nasopharyngeal cancer patients often have long-term toxicity associated with their care, and, thus, the availability of expertise and resources in management of this disease is important.”

Dr. Kimple disclosed relationships with Galera Therapeutics, Mele Associates, and Guidepoint Global. The guideline authors disclosed relationships with a range of pharmaceutical companies, as listed in the article.

New evidence-based recommendations provide guidance on when to give radiotherapy and chemotherapy to patients with nasopharyngeal carcinoma.

The guidelines, based on data from more than 100 studies, support offering intensity-modulated radiotherapy to all patients with stage II-IVA nasopharyngeal carcinoma. Recommendations for chemotherapy vary according to disease stage, tumor size, number of nodes, and contraindications.

The guidelines, released jointly by the Chinese Society of Clinical Oncology (CSCO) and the American Society of Clinical Oncology (ASCO), were published in the Journal of Clinical Oncology.

“For practicing oncologists in the United States, who often lack experience treating nasopharyngeal cancer, this guideline provides a useful, succinct summary of available evidence and expert recommendations. Nasopharyngeal cancer can be a technically and medically challenging disease to manage, and a multidisciplinary approach should be strongly encouraged,” said ASCO expert Randall J. Kimple, MD, PhD, of the University of Wisconsin–Madison.

“Much of the data guiding our treatment of these patients comes from endemic regions,” he continued. “How these data apply to patients in the U.S. remains a subject of ongoing study. Patients and providers should be encouraged to seek the opinion of a provider with expertise in the management of nasopharyngeal cancer.”

To compile “best practices” for treating nasopharyngeal carcinoma, the ASCO/CSCO expert panel conducted a literature search that included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2020. The panel identified 108 relevant studies and formulated their guidelines based on the evidence.
 

Recommendations

For all patients with stage II-IVA nasopharyngeal carcinoma, the guidelines recommend intensity-modulated radiation therapy with daily image guidance. The recommended dose is 70 Gy in 33-35 fractions over 7 weeks.

“This has been the standard approach at most institutions that treat a sufficient number of nasopharyngeal cancer patients each year,” Dr. Kimple said.

When adding chemotherapy to radiotherapy, two approaches are recommended. The first is induction chemotherapy followed by chemoradiation, and the second is chemoradiation followed by adjuvant chemotherapy.

“There are divergent opinions regarding the optimal approach in these patients, with slightly stronger data supporting the use of induction chemotherapy,” Dr. Kimple said. “For patients with earlier stage nasopharyngeal cancer (T1-2N1 or T2N0), chemotherapy can be offered, and is more strongly recommended for those with more advanced disease (T2N1, bulky disease, high EBV load).”

For patients receiving concurrent chemotherapy and radiotherapy, the recommended regimen is cisplatin given either weekly (40 mg/m²) or triweekly (100 mg/m²).

“The stated goal is to achieve a cumulative cisplatin dose in excess of 200 mg/m² regardless of the approach taken. Several options were provided for patients with a contraindication to cisplatin,” Dr. Kimple said.

Patients with contraindications can receive nedaplatin (100 mg/m² triweekly), carboplatin (area under curve, 5-6 triweekly), oxaliplatin (70 mg/m² weekly), or fluoropyrimidines (capecitabine, 5-fluorouracil, or tegafur).

For induction, the guidelines recommend platinum-based chemotherapy. Options include gemcitabine plus cisplatin, cisplatin plus 5-fluorouracil, cisplatin plus capecitabine, docetaxel plus cisplatin, and docetaxel plus cisplatin and 5-fluorouracil.

“[T]here is less strong evidence regarding the optimal induction chemotherapy approach for patients with nasopharyngeal cancer. Several possible regimens (doublet or triplet) are offered, with the use of platinum-based regimens being the common theme,” Dr. Kimple said.

For adjuvant chemotherapy, the guidelines recommend cisplatin plus 5-fluorouracil or carboplatin plus 5-fluorouracil.

The guidelines also suggest that clinicians take into account a patient’s other chronic conditions when formulating the treatment and follow-up plan.

“Patients with multiple chronic conditions pose a particular challenge to guideline-based care due to being commonly excluded from clinical trials,” Dr. Kimple said. “Shared decision-making plays a key role in the recommendations for patients with multiple chronic conditions. In addition, nasopharyngeal cancer patients often have long-term toxicity associated with their care, and, thus, the availability of expertise and resources in management of this disease is important.”

Dr. Kimple disclosed relationships with Galera Therapeutics, Mele Associates, and Guidepoint Global. The guideline authors disclosed relationships with a range of pharmaceutical companies, as listed in the article.

New evidence-based recommendations provide guidance on when to give radiotherapy and chemotherapy to patients with nasopharyngeal carcinoma.

The guidelines, based on data from more than 100 studies, support offering intensity-modulated radiotherapy to all patients with stage II-IVA nasopharyngeal carcinoma. Recommendations for chemotherapy vary according to disease stage, tumor size, number of nodes, and contraindications.

The guidelines, released jointly by the Chinese Society of Clinical Oncology (CSCO) and the American Society of Clinical Oncology (ASCO), were published in the Journal of Clinical Oncology.

“For practicing oncologists in the United States, who often lack experience treating nasopharyngeal cancer, this guideline provides a useful, succinct summary of available evidence and expert recommendations. Nasopharyngeal cancer can be a technically and medically challenging disease to manage, and a multidisciplinary approach should be strongly encouraged,” said ASCO expert Randall J. Kimple, MD, PhD, of the University of Wisconsin–Madison.

“Much of the data guiding our treatment of these patients comes from endemic regions,” he continued. “How these data apply to patients in the U.S. remains a subject of ongoing study. Patients and providers should be encouraged to seek the opinion of a provider with expertise in the management of nasopharyngeal cancer.”

To compile “best practices” for treating nasopharyngeal carcinoma, the ASCO/CSCO expert panel conducted a literature search that included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2020. The panel identified 108 relevant studies and formulated their guidelines based on the evidence.
 

Recommendations

For all patients with stage II-IVA nasopharyngeal carcinoma, the guidelines recommend intensity-modulated radiation therapy with daily image guidance. The recommended dose is 70 Gy in 33-35 fractions over 7 weeks.

“This has been the standard approach at most institutions that treat a sufficient number of nasopharyngeal cancer patients each year,” Dr. Kimple said.

When adding chemotherapy to radiotherapy, two approaches are recommended. The first is induction chemotherapy followed by chemoradiation, and the second is chemoradiation followed by adjuvant chemotherapy.

“There are divergent opinions regarding the optimal approach in these patients, with slightly stronger data supporting the use of induction chemotherapy,” Dr. Kimple said. “For patients with earlier stage nasopharyngeal cancer (T1-2N1 or T2N0), chemotherapy can be offered, and is more strongly recommended for those with more advanced disease (T2N1, bulky disease, high EBV load).”

For patients receiving concurrent chemotherapy and radiotherapy, the recommended regimen is cisplatin given either weekly (40 mg/m²) or triweekly (100 mg/m²).

“The stated goal is to achieve a cumulative cisplatin dose in excess of 200 mg/m² regardless of the approach taken. Several options were provided for patients with a contraindication to cisplatin,” Dr. Kimple said.

Patients with contraindications can receive nedaplatin (100 mg/m² triweekly), carboplatin (area under curve, 5-6 triweekly), oxaliplatin (70 mg/m² weekly), or fluoropyrimidines (capecitabine, 5-fluorouracil, or tegafur).

For induction, the guidelines recommend platinum-based chemotherapy. Options include gemcitabine plus cisplatin, cisplatin plus 5-fluorouracil, cisplatin plus capecitabine, docetaxel plus cisplatin, and docetaxel plus cisplatin and 5-fluorouracil.

“[T]here is less strong evidence regarding the optimal induction chemotherapy approach for patients with nasopharyngeal cancer. Several possible regimens (doublet or triplet) are offered, with the use of platinum-based regimens being the common theme,” Dr. Kimple said.

For adjuvant chemotherapy, the guidelines recommend cisplatin plus 5-fluorouracil or carboplatin plus 5-fluorouracil.

The guidelines also suggest that clinicians take into account a patient’s other chronic conditions when formulating the treatment and follow-up plan.

“Patients with multiple chronic conditions pose a particular challenge to guideline-based care due to being commonly excluded from clinical trials,” Dr. Kimple said. “Shared decision-making plays a key role in the recommendations for patients with multiple chronic conditions. In addition, nasopharyngeal cancer patients often have long-term toxicity associated with their care, and, thus, the availability of expertise and resources in management of this disease is important.”

Dr. Kimple disclosed relationships with Galera Therapeutics, Mele Associates, and Guidepoint Global. The guideline authors disclosed relationships with a range of pharmaceutical companies, as listed in the article.

New guidelines from the American Society of Clinical Oncology were released to address the treatment of advanced hepatocellular carcinoma (HCC).

An unprecedented number of new agents have been approved for systemic therapy of HCC in recent years, which led to a call for a revision of guidelines.

Prior to this influx of new therapies, there were no new treatments approved for HCC since the approval of sorafenib in 2005. In particular, the new guidelines include a recommendation for the use of a combination of the immunotherapy atezolizumab and the antiangiogenic agent bevacizumab for the first-line treatment of HCC.

To develop an evidence-based clinical practice guideline for advanced HCC, ASCO convened an expert panel. The panel conducted a systematic review of phase 3 randomized controlled trials (2007-2020) on systemic therapy for advanced HCC and developed recommendations based on the findings.

Nine phase 3 randomized controlled trials met the inclusion criteria.

The resulting ASCO guidelines were published in the Journal of Clinical Oncology
 

Highlights

“The major highlight of the guidelines is a recommendation for the combination of atezolizumab and bevacizumab for first-line therapy of most patients with advanced HCC. This combination was the first combination treatment using immunotherapy approved in this space,” said coauthor Muhammad Shaalan Beg, MD, of UT Southwestern Medical Center, Dallas.

“Multiple drug approvals for HCC mark a significant advancement in this disease which is historically considered recalcitrant. However, clinicians may have trouble selecting the right drug for the right patient at the right time in their disease course. The ASCO guidelines are geared towards providing clear guidance on how to incorporate these agents for patients with advanced HCC.”

The new guidelines state that where there are contraindications to atezolizumab/bevacizumab, tyrosine kinase inhibitors (TKIs) sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC. Following first-line treatment with atezolizumab/bevacizumab, and until better data are available, second-line therapy with a TKI may be recommended for appropriate candidates. Following first-line therapy with sorafenib or lenvatinib, second-line therapy options for appropriate candidates include cabozantinib, regorafenib for patients who previously tolerated sorafenib, or ramucirumab (for patients with alpha-fetoprotein ≥ 400 ng/mL), or atezolizumab/bevacizumab where patients did not have access to this option as first-line therapy.
 

Future directions

The guidelines also look to future directions in advanced HCC. “We will look at sequencing immuno-oncology and TKI agents. We await the results of key trials using immuno-oncology/TKI combinations and dual immuno-oncology combinations,” said Dr. Beg. “Molecular targeted treatments remind clinicians and researchers of the need for adequate tissue-based diagnosis of HCC.”

The guidelines note that clinicians need to take into account health disparities and cost considerations with HCC therapies. “HCC is a disease that disproportionately affects economically disadvantaged groups and underrepresented minority groups. The combination of atezolizumab/bevacizumab, approved for first-line therapy, may be a very high-cost treatment. Treatment will be limited to those with adequate health coverage/insurance. These factors can further increase the disparities in outcomes of HCC,” said Dr. Beg. He noted that risk factors of HCC include hepatitis C, alcohol-related liver disease, and cirrhosis.

“Health systems, insurance agencies, and clinicians need to pay particular attention to allow access of these drugs to patients. Early diagnosis and initiation of treatment are keys so that patients can be treated when their liver function is appropriate to enable good cancer outcomes,” added Dr. Beg.
 

Ongoing trials

Daneng Li, MD, of City of Hope, in Duarte, Calif., commented: “Patients who are eligible for the combination of atezolizumab and bevacizumab should be treated in the first line. This is the new standard of care as first-line treatment for advanced HCC. If there are contraindications, then either sorafenib or lenvatinib are an option for first-line treatment. This is very consistent with what practicing clinicians are starting to recognize.” He noted that there are no large phase 3 second-line trials of a TKI after lenvatinib or a frontline combination of atezolizumab/bevacizumab.

“The new guidelines are consistent with the recent rapid advances in the landscape for the treatment of advanced HCC. They can help community practitioners who might not see as many cases of advanced HCC keep up to date,” said Dr. Li.

“Research is rapidly progressing. Currently there are at least four major first-line combination trials with dual immuno-oncoIogy therapies or immuno-oncology plus a TKI. If any of those trials are positive, the guidelines will need to be revised immediately.”

Dr. Li added: “With multiple options available, we may be able to select the ideal combination for the individual patient. We now have good options for a disease that traditionally had a poor prognosis. I believe we are at a point of making more breakthroughs. Innovative combinations really allow these patients to live longer and better lives.”

Dr. Beg reported consulting and advising for Ipsen, Boston Biomedical, Array BioPharma, and AstraZeneca/MedImmune, and receiving research funding from numerous sources in industry. Dr. Li reported grant/research support to his institution from Boston Immunotherapeutics and consulting with Ipsen, Eisai, Exelixis, Roche-Genentech, and Merck.

New guidelines from the American Society of Clinical Oncology were released to address the treatment of advanced hepatocellular carcinoma (HCC).

An unprecedented number of new agents have been approved for systemic therapy of HCC in recent years, which led to a call for a revision of guidelines.

Prior to this influx of new therapies, there were no new treatments approved for HCC since the approval of sorafenib in 2005. In particular, the new guidelines include a recommendation for the use of a combination of the immunotherapy atezolizumab and the antiangiogenic agent bevacizumab for the first-line treatment of HCC.

To develop an evidence-based clinical practice guideline for advanced HCC, ASCO convened an expert panel. The panel conducted a systematic review of phase 3 randomized controlled trials (2007-2020) on systemic therapy for advanced HCC and developed recommendations based on the findings.

Nine phase 3 randomized controlled trials met the inclusion criteria.

The resulting ASCO guidelines were published in the Journal of Clinical Oncology
 

Highlights

“The major highlight of the guidelines is a recommendation for the combination of atezolizumab and bevacizumab for first-line therapy of most patients with advanced HCC. This combination was the first combination treatment using immunotherapy approved in this space,” said coauthor Muhammad Shaalan Beg, MD, of UT Southwestern Medical Center, Dallas.

“Multiple drug approvals for HCC mark a significant advancement in this disease which is historically considered recalcitrant. However, clinicians may have trouble selecting the right drug for the right patient at the right time in their disease course. The ASCO guidelines are geared towards providing clear guidance on how to incorporate these agents for patients with advanced HCC.”

The new guidelines state that where there are contraindications to atezolizumab/bevacizumab, tyrosine kinase inhibitors (TKIs) sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC. Following first-line treatment with atezolizumab/bevacizumab, and until better data are available, second-line therapy with a TKI may be recommended for appropriate candidates. Following first-line therapy with sorafenib or lenvatinib, second-line therapy options for appropriate candidates include cabozantinib, regorafenib for patients who previously tolerated sorafenib, or ramucirumab (for patients with alpha-fetoprotein ≥ 400 ng/mL), or atezolizumab/bevacizumab where patients did not have access to this option as first-line therapy.
 

Future directions

The guidelines also look to future directions in advanced HCC. “We will look at sequencing immuno-oncology and TKI agents. We await the results of key trials using immuno-oncology/TKI combinations and dual immuno-oncology combinations,” said Dr. Beg. “Molecular targeted treatments remind clinicians and researchers of the need for adequate tissue-based diagnosis of HCC.”

The guidelines note that clinicians need to take into account health disparities and cost considerations with HCC therapies. “HCC is a disease that disproportionately affects economically disadvantaged groups and underrepresented minority groups. The combination of atezolizumab/bevacizumab, approved for first-line therapy, may be a very high-cost treatment. Treatment will be limited to those with adequate health coverage/insurance. These factors can further increase the disparities in outcomes of HCC,” said Dr. Beg. He noted that risk factors of HCC include hepatitis C, alcohol-related liver disease, and cirrhosis.

“Health systems, insurance agencies, and clinicians need to pay particular attention to allow access of these drugs to patients. Early diagnosis and initiation of treatment are keys so that patients can be treated when their liver function is appropriate to enable good cancer outcomes,” added Dr. Beg.
 

Ongoing trials

Daneng Li, MD, of City of Hope, in Duarte, Calif., commented: “Patients who are eligible for the combination of atezolizumab and bevacizumab should be treated in the first line. This is the new standard of care as first-line treatment for advanced HCC. If there are contraindications, then either sorafenib or lenvatinib are an option for first-line treatment. This is very consistent with what practicing clinicians are starting to recognize.” He noted that there are no large phase 3 second-line trials of a TKI after lenvatinib or a frontline combination of atezolizumab/bevacizumab.

“The new guidelines are consistent with the recent rapid advances in the landscape for the treatment of advanced HCC. They can help community practitioners who might not see as many cases of advanced HCC keep up to date,” said Dr. Li.

“Research is rapidly progressing. Currently there are at least four major first-line combination trials with dual immuno-oncoIogy therapies or immuno-oncology plus a TKI. If any of those trials are positive, the guidelines will need to be revised immediately.”

Dr. Li added: “With multiple options available, we may be able to select the ideal combination for the individual patient. We now have good options for a disease that traditionally had a poor prognosis. I believe we are at a point of making more breakthroughs. Innovative combinations really allow these patients to live longer and better lives.”

Dr. Beg reported consulting and advising for Ipsen, Boston Biomedical, Array BioPharma, and AstraZeneca/MedImmune, and receiving research funding from numerous sources in industry. Dr. Li reported grant/research support to his institution from Boston Immunotherapeutics and consulting with Ipsen, Eisai, Exelixis, Roche-Genentech, and Merck.

New guidelines from the American Society of Clinical Oncology were released to address the treatment of advanced hepatocellular carcinoma (HCC).

An unprecedented number of new agents have been approved for systemic therapy of HCC in recent years, which led to a call for a revision of guidelines.

Prior to this influx of new therapies, there were no new treatments approved for HCC since the approval of sorafenib in 2005. In particular, the new guidelines include a recommendation for the use of a combination of the immunotherapy atezolizumab and the antiangiogenic agent bevacizumab for the first-line treatment of HCC.

To develop an evidence-based clinical practice guideline for advanced HCC, ASCO convened an expert panel. The panel conducted a systematic review of phase 3 randomized controlled trials (2007-2020) on systemic therapy for advanced HCC and developed recommendations based on the findings.

Nine phase 3 randomized controlled trials met the inclusion criteria.

The resulting ASCO guidelines were published in the Journal of Clinical Oncology
 

Highlights

“The major highlight of the guidelines is a recommendation for the combination of atezolizumab and bevacizumab for first-line therapy of most patients with advanced HCC. This combination was the first combination treatment using immunotherapy approved in this space,” said coauthor Muhammad Shaalan Beg, MD, of UT Southwestern Medical Center, Dallas.

“Multiple drug approvals for HCC mark a significant advancement in this disease which is historically considered recalcitrant. However, clinicians may have trouble selecting the right drug for the right patient at the right time in their disease course. The ASCO guidelines are geared towards providing clear guidance on how to incorporate these agents for patients with advanced HCC.”

The new guidelines state that where there are contraindications to atezolizumab/bevacizumab, tyrosine kinase inhibitors (TKIs) sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC. Following first-line treatment with atezolizumab/bevacizumab, and until better data are available, second-line therapy with a TKI may be recommended for appropriate candidates. Following first-line therapy with sorafenib or lenvatinib, second-line therapy options for appropriate candidates include cabozantinib, regorafenib for patients who previously tolerated sorafenib, or ramucirumab (for patients with alpha-fetoprotein ≥ 400 ng/mL), or atezolizumab/bevacizumab where patients did not have access to this option as first-line therapy.
 

Future directions

The guidelines also look to future directions in advanced HCC. “We will look at sequencing immuno-oncology and TKI agents. We await the results of key trials using immuno-oncology/TKI combinations and dual immuno-oncology combinations,” said Dr. Beg. “Molecular targeted treatments remind clinicians and researchers of the need for adequate tissue-based diagnosis of HCC.”

The guidelines note that clinicians need to take into account health disparities and cost considerations with HCC therapies. “HCC is a disease that disproportionately affects economically disadvantaged groups and underrepresented minority groups. The combination of atezolizumab/bevacizumab, approved for first-line therapy, may be a very high-cost treatment. Treatment will be limited to those with adequate health coverage/insurance. These factors can further increase the disparities in outcomes of HCC,” said Dr. Beg. He noted that risk factors of HCC include hepatitis C, alcohol-related liver disease, and cirrhosis.

“Health systems, insurance agencies, and clinicians need to pay particular attention to allow access of these drugs to patients. Early diagnosis and initiation of treatment are keys so that patients can be treated when their liver function is appropriate to enable good cancer outcomes,” added Dr. Beg.
 

Ongoing trials

Daneng Li, MD, of City of Hope, in Duarte, Calif., commented: “Patients who are eligible for the combination of atezolizumab and bevacizumab should be treated in the first line. This is the new standard of care as first-line treatment for advanced HCC. If there are contraindications, then either sorafenib or lenvatinib are an option for first-line treatment. This is very consistent with what practicing clinicians are starting to recognize.” He noted that there are no large phase 3 second-line trials of a TKI after lenvatinib or a frontline combination of atezolizumab/bevacizumab.

“The new guidelines are consistent with the recent rapid advances in the landscape for the treatment of advanced HCC. They can help community practitioners who might not see as many cases of advanced HCC keep up to date,” said Dr. Li.

“Research is rapidly progressing. Currently there are at least four major first-line combination trials with dual immuno-oncoIogy therapies or immuno-oncology plus a TKI. If any of those trials are positive, the guidelines will need to be revised immediately.”

Dr. Li added: “With multiple options available, we may be able to select the ideal combination for the individual patient. We now have good options for a disease that traditionally had a poor prognosis. I believe we are at a point of making more breakthroughs. Innovative combinations really allow these patients to live longer and better lives.”

Dr. Beg reported consulting and advising for Ipsen, Boston Biomedical, Array BioPharma, and AstraZeneca/MedImmune, and receiving research funding from numerous sources in industry. Dr. Li reported grant/research support to his institution from Boston Immunotherapeutics and consulting with Ipsen, Eisai, Exelixis, Roche-Genentech, and Merck.

New research suggests that proposed lung cancer screening guidelines could inadvertently increase racial and ethnic disparities, but adding in a risk prediction model could reduce some of these disparities by identifying people with high predicted benefit, regardless of race or ethnicity.

The draft United States Preventive Services Task Force (USPSTF) 2020 guidelines recommend annual lung cancer screening for individuals aged 50-80 who currently smoke or quit in the last 15 years, and who have a smoking history equivalent to at least one pack of cigarettes per day for 20 years or more.

This expands the age range and smoking history requirement compared to the 2013 USPSTF recommendations in an attempt to partially ameliorate racial disparities in screening eligibility. The 2013 guidelines recommend screening ever-smokers aged 55-80 with 30 or more pack-years and 15 or fewer quit-years.

However, neither the 2013 nor the 2020 USPSTF recommendations consider the higher risk of lung cancer and younger ages at diagnosis among African Americans, despite their smoking less than Whites, according to Rebecca Landy, PhD, of the National Cancer Institute in Bethesda, Md.

“For the same age and smoking history as Whites, minorities have substantially different lung cancer risk,” Dr. Landy said. “Incorporating individualized prediction models into USPSTF guidelines may reduce racial/ethnic disparities in lung cancer screening eligibility.”

Dr. Landy and colleagues set out to test that theory, and she presented the results at the 2020 World Congress on Lung Cancer (Abstract 3564), which was rescheduled for January 2021. The results were published in the Journal of the National Cancer Institute.
 

Study details

Dr. Landy and colleagues modeled the performance of National Lung Screening Trial–like screening (three annual CT screens, 5 years of follow-up) among three cohorts of ever-smokers aged 50-80 using the 2015 National Health Interview Survey.

One group was eligible by USPSTF 2013 guidelines, another by draft USPSTF 2020 guidelines, and yet another by augmenting the USPSTF 2020 guidelines using risk prediction to include individuals with 12 or more days of life gained according to the Life-Years From Screening–CT (LYFS-CT) model.

“Among each race/ethnicity, we calculated the number eligible for screening, proportion of preventable lung cancer deaths prevented, proportion of gainable life-years gained, and screening effectiveness, as well as the relative disparities in lung cancer deaths prevented and life-years gained,” Dr. Landy said.
 

Results

Under the 2013 guidelines, 8 million ever-smokers were eligible. The disparities in lung cancer death sensitivity, compared to Whites, were 15% for African Americans, 15% for Asian Americans, and 24% for Hispanic Americans. Disparities for life-year gained sensitivity were 15%, 13%, and 24%, respectively.

Under the 2020 draft guidelines, 14.5 million ever-smokers were eligible, but racial/ethnic disparities persisted. Disparities in lung cancer death sensitivity were 13% for African Americans, 19% for Asian Americans, and 27% for Hispanic Americans. Disparities for life-year gained sensitivity were 16%, 19%, and 27%, respectively.

Using the LYFS-CT predictive-risk model added an additional 3.5 million people and “nearly eliminated” disparities for African Americans, Dr. Landy noted. However, disparities persisted for Asian Americans and Hispanic Americans.

Disparities in lung cancer death sensitivity were 0% for African Americans, 19% for Asian Americans, and 23% for Hispanic Americans. Disparities for life-year gained sensitivity were 1%, 19%, and 24%, respectively.
 

More and widening disparity

The results showed that augmenting USPSTF criteria to include high-benefit people selected significantly more African Americans than Whites and could therefore reduce or even eliminate disparities between Whites and African Americans.

“The 2020 USPSTF draft recommendations would make 6.5 million more people eligible to be screened, in addition to the 8 million from the 2013 criteria,” said Gerard Silvestri, MD, of the Medical University of South Carolina, Charleston, who was not involved in this study.

“But there will be more White people than African American people added, and the disparity between them may widen. Using the risk prediction model outlined in this well-researched study could close the gap in disparity. It’s important to identify individual risk and life expectancy.”

Dr. Silvestri pointed out that, compared to Whites, African Americans develop lung cancer at an earlier age with fewer pack-years history of smoking and have worse outcomes.

“We can’t just focus on one aspect of disparity,” he said. “African Americans are much less likely to be insured or to identify a primary care provider for integrated care. We know that screening works. The 2020 USPSTF draft recommendations will enlarge the pool of eligible African Americans and reduce disparities if the other part of the equation holds; that is, they get access to care and screening.”

This study was funded by the National Institutes of Health/National Cancer Institute. Dr. Landy and Dr. Silvestri have no disclosures.

New research suggests that proposed lung cancer screening guidelines could inadvertently increase racial and ethnic disparities, but adding in a risk prediction model could reduce some of these disparities by identifying people with high predicted benefit, regardless of race or ethnicity.

The draft United States Preventive Services Task Force (USPSTF) 2020 guidelines recommend annual lung cancer screening for individuals aged 50-80 who currently smoke or quit in the last 15 years, and who have a smoking history equivalent to at least one pack of cigarettes per day for 20 years or more.

This expands the age range and smoking history requirement compared to the 2013 USPSTF recommendations in an attempt to partially ameliorate racial disparities in screening eligibility. The 2013 guidelines recommend screening ever-smokers aged 55-80 with 30 or more pack-years and 15 or fewer quit-years.

However, neither the 2013 nor the 2020 USPSTF recommendations consider the higher risk of lung cancer and younger ages at diagnosis among African Americans, despite their smoking less than Whites, according to Rebecca Landy, PhD, of the National Cancer Institute in Bethesda, Md.

“For the same age and smoking history as Whites, minorities have substantially different lung cancer risk,” Dr. Landy said. “Incorporating individualized prediction models into USPSTF guidelines may reduce racial/ethnic disparities in lung cancer screening eligibility.”

Dr. Landy and colleagues set out to test that theory, and she presented the results at the 2020 World Congress on Lung Cancer (Abstract 3564), which was rescheduled for January 2021. The results were published in the Journal of the National Cancer Institute.
 

Study details

Dr. Landy and colleagues modeled the performance of National Lung Screening Trial–like screening (three annual CT screens, 5 years of follow-up) among three cohorts of ever-smokers aged 50-80 using the 2015 National Health Interview Survey.

One group was eligible by USPSTF 2013 guidelines, another by draft USPSTF 2020 guidelines, and yet another by augmenting the USPSTF 2020 guidelines using risk prediction to include individuals with 12 or more days of life gained according to the Life-Years From Screening–CT (LYFS-CT) model.

“Among each race/ethnicity, we calculated the number eligible for screening, proportion of preventable lung cancer deaths prevented, proportion of gainable life-years gained, and screening effectiveness, as well as the relative disparities in lung cancer deaths prevented and life-years gained,” Dr. Landy said.
 

Results

Under the 2013 guidelines, 8 million ever-smokers were eligible. The disparities in lung cancer death sensitivity, compared to Whites, were 15% for African Americans, 15% for Asian Americans, and 24% for Hispanic Americans. Disparities for life-year gained sensitivity were 15%, 13%, and 24%, respectively.

Under the 2020 draft guidelines, 14.5 million ever-smokers were eligible, but racial/ethnic disparities persisted. Disparities in lung cancer death sensitivity were 13% for African Americans, 19% for Asian Americans, and 27% for Hispanic Americans. Disparities for life-year gained sensitivity were 16%, 19%, and 27%, respectively.

Using the LYFS-CT predictive-risk model added an additional 3.5 million people and “nearly eliminated” disparities for African Americans, Dr. Landy noted. However, disparities persisted for Asian Americans and Hispanic Americans.

Disparities in lung cancer death sensitivity were 0% for African Americans, 19% for Asian Americans, and 23% for Hispanic Americans. Disparities for life-year gained sensitivity were 1%, 19%, and 24%, respectively.
 

More and widening disparity

The results showed that augmenting USPSTF criteria to include high-benefit people selected significantly more African Americans than Whites and could therefore reduce or even eliminate disparities between Whites and African Americans.

“The 2020 USPSTF draft recommendations would make 6.5 million more people eligible to be screened, in addition to the 8 million from the 2013 criteria,” said Gerard Silvestri, MD, of the Medical University of South Carolina, Charleston, who was not involved in this study.

“But there will be more White people than African American people added, and the disparity between them may widen. Using the risk prediction model outlined in this well-researched study could close the gap in disparity. It’s important to identify individual risk and life expectancy.”

Dr. Silvestri pointed out that, compared to Whites, African Americans develop lung cancer at an earlier age with fewer pack-years history of smoking and have worse outcomes.

“We can’t just focus on one aspect of disparity,” he said. “African Americans are much less likely to be insured or to identify a primary care provider for integrated care. We know that screening works. The 2020 USPSTF draft recommendations will enlarge the pool of eligible African Americans and reduce disparities if the other part of the equation holds; that is, they get access to care and screening.”

This study was funded by the National Institutes of Health/National Cancer Institute. Dr. Landy and Dr. Silvestri have no disclosures.

New research suggests that proposed lung cancer screening guidelines could inadvertently increase racial and ethnic disparities, but adding in a risk prediction model could reduce some of these disparities by identifying people with high predicted benefit, regardless of race or ethnicity.

The draft United States Preventive Services Task Force (USPSTF) 2020 guidelines recommend annual lung cancer screening for individuals aged 50-80 who currently smoke or quit in the last 15 years, and who have a smoking history equivalent to at least one pack of cigarettes per day for 20 years or more.

This expands the age range and smoking history requirement compared to the 2013 USPSTF recommendations in an attempt to partially ameliorate racial disparities in screening eligibility. The 2013 guidelines recommend screening ever-smokers aged 55-80 with 30 or more pack-years and 15 or fewer quit-years.

However, neither the 2013 nor the 2020 USPSTF recommendations consider the higher risk of lung cancer and younger ages at diagnosis among African Americans, despite their smoking less than Whites, according to Rebecca Landy, PhD, of the National Cancer Institute in Bethesda, Md.

“For the same age and smoking history as Whites, minorities have substantially different lung cancer risk,” Dr. Landy said. “Incorporating individualized prediction models into USPSTF guidelines may reduce racial/ethnic disparities in lung cancer screening eligibility.”

Dr. Landy and colleagues set out to test that theory, and she presented the results at the 2020 World Congress on Lung Cancer (Abstract 3564), which was rescheduled for January 2021. The results were published in the Journal of the National Cancer Institute.
 

Study details

Dr. Landy and colleagues modeled the performance of National Lung Screening Trial–like screening (three annual CT screens, 5 years of follow-up) among three cohorts of ever-smokers aged 50-80 using the 2015 National Health Interview Survey.

One group was eligible by USPSTF 2013 guidelines, another by draft USPSTF 2020 guidelines, and yet another by augmenting the USPSTF 2020 guidelines using risk prediction to include individuals with 12 or more days of life gained according to the Life-Years From Screening–CT (LYFS-CT) model.

“Among each race/ethnicity, we calculated the number eligible for screening, proportion of preventable lung cancer deaths prevented, proportion of gainable life-years gained, and screening effectiveness, as well as the relative disparities in lung cancer deaths prevented and life-years gained,” Dr. Landy said.
 

Results

Under the 2013 guidelines, 8 million ever-smokers were eligible. The disparities in lung cancer death sensitivity, compared to Whites, were 15% for African Americans, 15% for Asian Americans, and 24% for Hispanic Americans. Disparities for life-year gained sensitivity were 15%, 13%, and 24%, respectively.

Under the 2020 draft guidelines, 14.5 million ever-smokers were eligible, but racial/ethnic disparities persisted. Disparities in lung cancer death sensitivity were 13% for African Americans, 19% for Asian Americans, and 27% for Hispanic Americans. Disparities for life-year gained sensitivity were 16%, 19%, and 27%, respectively.

Using the LYFS-CT predictive-risk model added an additional 3.5 million people and “nearly eliminated” disparities for African Americans, Dr. Landy noted. However, disparities persisted for Asian Americans and Hispanic Americans.

Disparities in lung cancer death sensitivity were 0% for African Americans, 19% for Asian Americans, and 23% for Hispanic Americans. Disparities for life-year gained sensitivity were 1%, 19%, and 24%, respectively.
 

More and widening disparity

The results showed that augmenting USPSTF criteria to include high-benefit people selected significantly more African Americans than Whites and could therefore reduce or even eliminate disparities between Whites and African Americans.

“The 2020 USPSTF draft recommendations would make 6.5 million more people eligible to be screened, in addition to the 8 million from the 2013 criteria,” said Gerard Silvestri, MD, of the Medical University of South Carolina, Charleston, who was not involved in this study.

“But there will be more White people than African American people added, and the disparity between them may widen. Using the risk prediction model outlined in this well-researched study could close the gap in disparity. It’s important to identify individual risk and life expectancy.”

Dr. Silvestri pointed out that, compared to Whites, African Americans develop lung cancer at an earlier age with fewer pack-years history of smoking and have worse outcomes.

“We can’t just focus on one aspect of disparity,” he said. “African Americans are much less likely to be insured or to identify a primary care provider for integrated care. We know that screening works. The 2020 USPSTF draft recommendations will enlarge the pool of eligible African Americans and reduce disparities if the other part of the equation holds; that is, they get access to care and screening.”

This study was funded by the National Institutes of Health/National Cancer Institute. Dr. Landy and Dr. Silvestri have no disclosures.

Tailoring adjuvant chemotherapy based on the expression of two molecular markers did not confer a survival advantage in patients with completely resected stage II-III non–small cell lung cancer (NSCLC) in a phase 3 trial.

The patients were randomized to receive investigator’s choice of platinum-based chemotherapy or treatment tailored according to messenger RNA (mRNA) expression of two molecular markers – excision repair cross complementation 1 (ERCC1) and thymidylate synthase (TS).

There was no significant difference in overall survival or recurrence-free survival between the treatment approaches. However, toxicity was less common among patients who received customized treatment.

These results, from the phase 3 ITACA trial, were presented at the 2020 World Conference on Lung Cancer (Abstract 1820), which was rescheduled to January 2021.

“There is a clear need to define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy,” said presenter Silvia Novello, MD, PhD, of the University of Turin in Italy. “mRNA expression of different genes has been correlated with the sensitivity or resistance to specific anticancer agents.”

With this in mind, Dr. Novello and colleagues conducted the ITACA trial. The researchers’ primary goal was to determine whether an adjuvant pharmacogenomic-driven approach was able to improve overall survival in completely resected NSCLC.
 

Patients and treatment

The researchers randomized 773 NSCLC patients within 5-8 weeks after radical surgery. Genomic analyses were performed soon after surgery, and patients were randomly assigned to investigator’s choice of platinum-based chemotherapy or to tailored treatments defined by mRNA levels of ERCC1 and TS.

Patients with high ERCC1 mRNA expression who were randomized to tailored treatment received single-agent docetaxel if their TS level was high or pemetrexed monotherapy if their TS level was low.

Patients with low ERCC1 mRNA expression who were randomized to tailored treatment received cisplatin-gemcitabine if their TS level was high or cisplatin-pemetrexed if their TS was low.

The most frequent doublets used in control patients were cisplatin-gemcitabine and cisplatin-vinorelbine.

The demographic characteristics of the 384 patients randomized to tailored therapy and the 389 control subjects were well-balanced, Dr. Novello said. Two-thirds of patients had stage II disease, 11% were never smokers, and the vast majority had a lobectomy as the resection method.
 

Results

At a median follow-up of 28.2 months, the median overall survival was 96.4 months in the tailored therapy arm and 83.5 months in the control arm. The median recurrence-free survival was 64.4 months and 41.5 months, respectively.

“Adjuvant chemotherapy customization based on the primary tumor tissue mRNA expression of ERCC1 and TS did not significantly improve overall survival or recurrence-free survival,” Dr. Novello said. “There was a non–statistically significant trend for overall survival favoring the customized arm.”

Dr. Novello noted that, when the final analysis was performed, the study was underpowered, as only 46% of expected events were collected. Assuming the same hazard ratio point estimate and that the expected 336 events were collected, the hazard ratio estimate would be 0.76 (P = .012).

Grade 3/4 toxicities occurred in 32.6% of patients in the tailored therapy arm and 45.9% of those in the control arm (P < .001).

“It is important to underline that the treatment customization significantly improved the toxicity profile without compromising the efficacy,” Dr. Novello said.

She added that “more comprehensive and high-throughput diagnostic techniques will be needed in order to tailor adjuvant chemotherapy, with or without immunotherapy, in completely resected NSCLC.”

“The ITACA study is the largest adjuvant study tailored to ERCC1/TS status, and the results have been long-awaited,” said Tetsuya Mitsudomi, MD, a professor at Kindai University in Japan and president of the International Association for the Study of Lung Cancer.

“This trial should be praised for the mandated genomic analysis that was accomplished within a reasonably short time frame before random assignment. In addition, this trial confirmed that there is no biomarker strong enough to predict the efficacy of cytotoxic chemotherapy. However, the concept of customizing adjuvant therapy according to the genomic status of patients’ tumors is valid, leading to the recent demonstration in the ADAURA study of the superiority of osimertinib in delaying the postoperative recurrence of disease in patients with EGFR-mutated NSCLC.”

The ITACA study was funded by University of Turin and Eli Lilly. Dr. Novello disclosed relationships with Eli Lilly, Amgen, AstraZeneca, Bohringer Ingelheim, Beigene, Pfizer, Roche, Merck, Bristol-Myers Squibb, Takeda, and Sanofi. Dr. Mitsudomi disclosed relationships with Eli Lilly, AstraZeneca, Boehringer-Ingelheim, Chugai, Pfizer, Merck, Ono Pharmaceutical, Bristol-Myers Squibb, Novartis, ThermoFisher, Guardant, Eisai, Amgen, and Johnson & Johnson.

Tailoring adjuvant chemotherapy based on the expression of two molecular markers did not confer a survival advantage in patients with completely resected stage II-III non–small cell lung cancer (NSCLC) in a phase 3 trial.

The patients were randomized to receive investigator’s choice of platinum-based chemotherapy or treatment tailored according to messenger RNA (mRNA) expression of two molecular markers – excision repair cross complementation 1 (ERCC1) and thymidylate synthase (TS).

There was no significant difference in overall survival or recurrence-free survival between the treatment approaches. However, toxicity was less common among patients who received customized treatment.

These results, from the phase 3 ITACA trial, were presented at the 2020 World Conference on Lung Cancer (Abstract 1820), which was rescheduled to January 2021.

“There is a clear need to define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy,” said presenter Silvia Novello, MD, PhD, of the University of Turin in Italy. “mRNA expression of different genes has been correlated with the sensitivity or resistance to specific anticancer agents.”

With this in mind, Dr. Novello and colleagues conducted the ITACA trial. The researchers’ primary goal was to determine whether an adjuvant pharmacogenomic-driven approach was able to improve overall survival in completely resected NSCLC.
 

Patients and treatment

The researchers randomized 773 NSCLC patients within 5-8 weeks after radical surgery. Genomic analyses were performed soon after surgery, and patients were randomly assigned to investigator’s choice of platinum-based chemotherapy or to tailored treatments defined by mRNA levels of ERCC1 and TS.

Patients with high ERCC1 mRNA expression who were randomized to tailored treatment received single-agent docetaxel if their TS level was high or pemetrexed monotherapy if their TS level was low.

Patients with low ERCC1 mRNA expression who were randomized to tailored treatment received cisplatin-gemcitabine if their TS level was high or cisplatin-pemetrexed if their TS was low.

The most frequent doublets used in control patients were cisplatin-gemcitabine and cisplatin-vinorelbine.

The demographic characteristics of the 384 patients randomized to tailored therapy and the 389 control subjects were well-balanced, Dr. Novello said. Two-thirds of patients had stage II disease, 11% were never smokers, and the vast majority had a lobectomy as the resection method.
 

Results

At a median follow-up of 28.2 months, the median overall survival was 96.4 months in the tailored therapy arm and 83.5 months in the control arm. The median recurrence-free survival was 64.4 months and 41.5 months, respectively.

“Adjuvant chemotherapy customization based on the primary tumor tissue mRNA expression of ERCC1 and TS did not significantly improve overall survival or recurrence-free survival,” Dr. Novello said. “There was a non–statistically significant trend for overall survival favoring the customized arm.”

Dr. Novello noted that, when the final analysis was performed, the study was underpowered, as only 46% of expected events were collected. Assuming the same hazard ratio point estimate and that the expected 336 events were collected, the hazard ratio estimate would be 0.76 (P = .012).

Grade 3/4 toxicities occurred in 32.6% of patients in the tailored therapy arm and 45.9% of those in the control arm (P < .001).

“It is important to underline that the treatment customization significantly improved the toxicity profile without compromising the efficacy,” Dr. Novello said.

She added that “more comprehensive and high-throughput diagnostic techniques will be needed in order to tailor adjuvant chemotherapy, with or without immunotherapy, in completely resected NSCLC.”

“The ITACA study is the largest adjuvant study tailored to ERCC1/TS status, and the results have been long-awaited,” said Tetsuya Mitsudomi, MD, a professor at Kindai University in Japan and president of the International Association for the Study of Lung Cancer.

“This trial should be praised for the mandated genomic analysis that was accomplished within a reasonably short time frame before random assignment. In addition, this trial confirmed that there is no biomarker strong enough to predict the efficacy of cytotoxic chemotherapy. However, the concept of customizing adjuvant therapy according to the genomic status of patients’ tumors is valid, leading to the recent demonstration in the ADAURA study of the superiority of osimertinib in delaying the postoperative recurrence of disease in patients with EGFR-mutated NSCLC.”

The ITACA study was funded by University of Turin and Eli Lilly. Dr. Novello disclosed relationships with Eli Lilly, Amgen, AstraZeneca, Bohringer Ingelheim, Beigene, Pfizer, Roche, Merck, Bristol-Myers Squibb, Takeda, and Sanofi. Dr. Mitsudomi disclosed relationships with Eli Lilly, AstraZeneca, Boehringer-Ingelheim, Chugai, Pfizer, Merck, Ono Pharmaceutical, Bristol-Myers Squibb, Novartis, ThermoFisher, Guardant, Eisai, Amgen, and Johnson & Johnson.

Tailoring adjuvant chemotherapy based on the expression of two molecular markers did not confer a survival advantage in patients with completely resected stage II-III non–small cell lung cancer (NSCLC) in a phase 3 trial.

The patients were randomized to receive investigator’s choice of platinum-based chemotherapy or treatment tailored according to messenger RNA (mRNA) expression of two molecular markers – excision repair cross complementation 1 (ERCC1) and thymidylate synthase (TS).

There was no significant difference in overall survival or recurrence-free survival between the treatment approaches. However, toxicity was less common among patients who received customized treatment.

These results, from the phase 3 ITACA trial, were presented at the 2020 World Conference on Lung Cancer (Abstract 1820), which was rescheduled to January 2021.

“There is a clear need to define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy,” said presenter Silvia Novello, MD, PhD, of the University of Turin in Italy. “mRNA expression of different genes has been correlated with the sensitivity or resistance to specific anticancer agents.”

With this in mind, Dr. Novello and colleagues conducted the ITACA trial. The researchers’ primary goal was to determine whether an adjuvant pharmacogenomic-driven approach was able to improve overall survival in completely resected NSCLC.
 

Patients and treatment

The researchers randomized 773 NSCLC patients within 5-8 weeks after radical surgery. Genomic analyses were performed soon after surgery, and patients were randomly assigned to investigator’s choice of platinum-based chemotherapy or to tailored treatments defined by mRNA levels of ERCC1 and TS.

Patients with high ERCC1 mRNA expression who were randomized to tailored treatment received single-agent docetaxel if their TS level was high or pemetrexed monotherapy if their TS level was low.

Patients with low ERCC1 mRNA expression who were randomized to tailored treatment received cisplatin-gemcitabine if their TS level was high or cisplatin-pemetrexed if their TS was low.

The most frequent doublets used in control patients were cisplatin-gemcitabine and cisplatin-vinorelbine.

The demographic characteristics of the 384 patients randomized to tailored therapy and the 389 control subjects were well-balanced, Dr. Novello said. Two-thirds of patients had stage II disease, 11% were never smokers, and the vast majority had a lobectomy as the resection method.
 

Results

At a median follow-up of 28.2 months, the median overall survival was 96.4 months in the tailored therapy arm and 83.5 months in the control arm. The median recurrence-free survival was 64.4 months and 41.5 months, respectively.

“Adjuvant chemotherapy customization based on the primary tumor tissue mRNA expression of ERCC1 and TS did not significantly improve overall survival or recurrence-free survival,” Dr. Novello said. “There was a non–statistically significant trend for overall survival favoring the customized arm.”

Dr. Novello noted that, when the final analysis was performed, the study was underpowered, as only 46% of expected events were collected. Assuming the same hazard ratio point estimate and that the expected 336 events were collected, the hazard ratio estimate would be 0.76 (P = .012).

Grade 3/4 toxicities occurred in 32.6% of patients in the tailored therapy arm and 45.9% of those in the control arm (P < .001).

“It is important to underline that the treatment customization significantly improved the toxicity profile without compromising the efficacy,” Dr. Novello said.

She added that “more comprehensive and high-throughput diagnostic techniques will be needed in order to tailor adjuvant chemotherapy, with or without immunotherapy, in completely resected NSCLC.”

“The ITACA study is the largest adjuvant study tailored to ERCC1/TS status, and the results have been long-awaited,” said Tetsuya Mitsudomi, MD, a professor at Kindai University in Japan and president of the International Association for the Study of Lung Cancer.

“This trial should be praised for the mandated genomic analysis that was accomplished within a reasonably short time frame before random assignment. In addition, this trial confirmed that there is no biomarker strong enough to predict the efficacy of cytotoxic chemotherapy. However, the concept of customizing adjuvant therapy according to the genomic status of patients’ tumors is valid, leading to the recent demonstration in the ADAURA study of the superiority of osimertinib in delaying the postoperative recurrence of disease in patients with EGFR-mutated NSCLC.”

The ITACA study was funded by University of Turin and Eli Lilly. Dr. Novello disclosed relationships with Eli Lilly, Amgen, AstraZeneca, Bohringer Ingelheim, Beigene, Pfizer, Roche, Merck, Bristol-Myers Squibb, Takeda, and Sanofi. Dr. Mitsudomi disclosed relationships with Eli Lilly, AstraZeneca, Boehringer-Ingelheim, Chugai, Pfizer, Merck, Ono Pharmaceutical, Bristol-Myers Squibb, Novartis, ThermoFisher, Guardant, Eisai, Amgen, and Johnson & Johnson.

Concurrent cisplatin should remain the standard treatment over cetuximab for patients with locoregionally advanced head and neck squamous cell carcinoma, according to a large comparative phase 3 trial.

Based on the results of an interim analysis of the ARTSCAN III clinical trial, the independent safety data monitoring committee recommended early closure of the study because the results of the study suggest that cetuximab may be inferior to cisplatin.

“This study supports previous retrospective and prospective studies that suggest that concurrent cisplatin with radiation is superior to regimens with concurrent cetuximab in locally advanced head and neck cancers,” commented Sachin Jhawar, MD, MSCI, assistant professor in the department of radiation oncology at Ohio State University Comprehensive Cancer Center, Columbus. “While the previous studies De-ESCALaTE HPV and RTOG 1016 were specific to HPV [human papillomavirus]-positive cancers, this study allowed non–virally mediated tumors, though the majority of cases were HPV related.”

The new study also used a lower-dose weekly regimen of cisplatin than the other two studies, noted Dr. Jhawar. Early trials used a cisplatin dose of 100 mg/m² every 3 weeks, but “the field is moving toward a dose of 40 mg/m² weekly, the dose use in the Swedish study. This study had an interesting second randomization of radiation dose-escalation for more advanced primary T stage tumors, but because the study ended early it is difficult to fully interpret those results.”

Swedish researchers, led by Maria Gebre-Medhin, MD, PhD, department of hematology, oncology, and radiation physics, Skåne University Hospital, Lund, Sweden, performed an open-label, randomized, controlled, phase 3 study of patients with locoregionally advanced head and neck squamous cell carcinoma. The patients received IV cetuximab 400 mg/m² 1 week before the start of radiation therapy followed by 250 mg/m² per week, or weekly IV cisplatin 40 mg/m² during radiation therapy.

The study results were published in the Journal of Clinical Oncology.

The study was prematurely closed after an unplanned interim analysis when 298 patients had been randomly assigned. The cumulative incidence of locoregional failures at 3 years was more than twice as high in the cetuximab group (23%), compared with the cisplatin group (9%; P = .0036). At 3 years, overall survival was higher in the cisplatin (88%) group than in the cetuximab group (78%), but the difference was not significant (P = .086). The cumulative incidence of distant failures did not differ between the treatment groups, and the toxicity burden was similar.

“Concurrent cisplatin led to improved locoregional control and event-free survival with a trend toward improved overall survival. The types of toxicity were different, as would be expected with the different drug mechanisms, but the rate of toxicity was not,” said Dr. Dr. Jhawar. “Interestingly, the benefit of cisplatin seemed to be limited to patients with p16-positive oropharyngeal cancer. There was clinical equipoise in the p16-negative oropharyngeal cancer group and in the non–oropharyngeal cancer group. The numbers were small, but this is intriguing and suggests that there is more work to be done in this group of patients to tease out if we can escalate or use alternative therapy.”

Cisplatin has been repeatedly proven to be superior in selected populations. The next steps, said Dr. Jhawar, include defining “optimal regimens in cisplatin-ineligible populations based on age, performance status, kidney function, hearing loss, neuropathy, and HIV/AIDS; improvements with new targeted therapies and immunotherapies; and deescalation of systemic and/or radiation regimens in the best outcome groups, such as low-risk HPV-positive patients. And we are going to see more personalized medicine with genetic testing of tumors.”

When patients are ineligible for cisplatin, no optimal regimens have been defined as yet. At Ohio State, Dr. Jhawar and colleagues use carboplatin therapy.

For practicing oncologists, Dr. Jhawar said the bottom line is “patients who are eligible should receive concurrent cisplatin therapy for locoregionally advanced head and neck cancer.”

The ARTSCAN III study was funded by the Swedish Cancer Society and the Mrs. Berta Kamprad Cancer Foundation. One of the study’s coauthors reported a leadership role in ScandiDos. The other authors reported they had no conflicts. Dr. Jhawar reported he had no conflicts of interest.




 

Concurrent cisplatin should remain the standard treatment over cetuximab for patients with locoregionally advanced head and neck squamous cell carcinoma, according to a large comparative phase 3 trial.

Based on the results of an interim analysis of the ARTSCAN III clinical trial, the independent safety data monitoring committee recommended early closure of the study because the results of the study suggest that cetuximab may be inferior to cisplatin.

“This study supports previous retrospective and prospective studies that suggest that concurrent cisplatin with radiation is superior to regimens with concurrent cetuximab in locally advanced head and neck cancers,” commented Sachin Jhawar, MD, MSCI, assistant professor in the department of radiation oncology at Ohio State University Comprehensive Cancer Center, Columbus. “While the previous studies De-ESCALaTE HPV and RTOG 1016 were specific to HPV [human papillomavirus]-positive cancers, this study allowed non–virally mediated tumors, though the majority of cases were HPV related.”

The new study also used a lower-dose weekly regimen of cisplatin than the other two studies, noted Dr. Jhawar. Early trials used a cisplatin dose of 100 mg/m² every 3 weeks, but “the field is moving toward a dose of 40 mg/m² weekly, the dose use in the Swedish study. This study had an interesting second randomization of radiation dose-escalation for more advanced primary T stage tumors, but because the study ended early it is difficult to fully interpret those results.”

Swedish researchers, led by Maria Gebre-Medhin, MD, PhD, department of hematology, oncology, and radiation physics, Skåne University Hospital, Lund, Sweden, performed an open-label, randomized, controlled, phase 3 study of patients with locoregionally advanced head and neck squamous cell carcinoma. The patients received IV cetuximab 400 mg/m² 1 week before the start of radiation therapy followed by 250 mg/m² per week, or weekly IV cisplatin 40 mg/m² during radiation therapy.

The study results were published in the Journal of Clinical Oncology.

The study was prematurely closed after an unplanned interim analysis when 298 patients had been randomly assigned. The cumulative incidence of locoregional failures at 3 years was more than twice as high in the cetuximab group (23%), compared with the cisplatin group (9%; P = .0036). At 3 years, overall survival was higher in the cisplatin (88%) group than in the cetuximab group (78%), but the difference was not significant (P = .086). The cumulative incidence of distant failures did not differ between the treatment groups, and the toxicity burden was similar.

“Concurrent cisplatin led to improved locoregional control and event-free survival with a trend toward improved overall survival. The types of toxicity were different, as would be expected with the different drug mechanisms, but the rate of toxicity was not,” said Dr. Dr. Jhawar. “Interestingly, the benefit of cisplatin seemed to be limited to patients with p16-positive oropharyngeal cancer. There was clinical equipoise in the p16-negative oropharyngeal cancer group and in the non–oropharyngeal cancer group. The numbers were small, but this is intriguing and suggests that there is more work to be done in this group of patients to tease out if we can escalate or use alternative therapy.”

Cisplatin has been repeatedly proven to be superior in selected populations. The next steps, said Dr. Jhawar, include defining “optimal regimens in cisplatin-ineligible populations based on age, performance status, kidney function, hearing loss, neuropathy, and HIV/AIDS; improvements with new targeted therapies and immunotherapies; and deescalation of systemic and/or radiation regimens in the best outcome groups, such as low-risk HPV-positive patients. And we are going to see more personalized medicine with genetic testing of tumors.”

When patients are ineligible for cisplatin, no optimal regimens have been defined as yet. At Ohio State, Dr. Jhawar and colleagues use carboplatin therapy.

For practicing oncologists, Dr. Jhawar said the bottom line is “patients who are eligible should receive concurrent cisplatin therapy for locoregionally advanced head and neck cancer.”

The ARTSCAN III study was funded by the Swedish Cancer Society and the Mrs. Berta Kamprad Cancer Foundation. One of the study’s coauthors reported a leadership role in ScandiDos. The other authors reported they had no conflicts. Dr. Jhawar reported he had no conflicts of interest.




 

Concurrent cisplatin should remain the standard treatment over cetuximab for patients with locoregionally advanced head and neck squamous cell carcinoma, according to a large comparative phase 3 trial.

Based on the results of an interim analysis of the ARTSCAN III clinical trial, the independent safety data monitoring committee recommended early closure of the study because the results of the study suggest that cetuximab may be inferior to cisplatin.

“This study supports previous retrospective and prospective studies that suggest that concurrent cisplatin with radiation is superior to regimens with concurrent cetuximab in locally advanced head and neck cancers,” commented Sachin Jhawar, MD, MSCI, assistant professor in the department of radiation oncology at Ohio State University Comprehensive Cancer Center, Columbus. “While the previous studies De-ESCALaTE HPV and RTOG 1016 were specific to HPV [human papillomavirus]-positive cancers, this study allowed non–virally mediated tumors, though the majority of cases were HPV related.”

The new study also used a lower-dose weekly regimen of cisplatin than the other two studies, noted Dr. Jhawar. Early trials used a cisplatin dose of 100 mg/m² every 3 weeks, but “the field is moving toward a dose of 40 mg/m² weekly, the dose use in the Swedish study. This study had an interesting second randomization of radiation dose-escalation for more advanced primary T stage tumors, but because the study ended early it is difficult to fully interpret those results.”

Swedish researchers, led by Maria Gebre-Medhin, MD, PhD, department of hematology, oncology, and radiation physics, Skåne University Hospital, Lund, Sweden, performed an open-label, randomized, controlled, phase 3 study of patients with locoregionally advanced head and neck squamous cell carcinoma. The patients received IV cetuximab 400 mg/m² 1 week before the start of radiation therapy followed by 250 mg/m² per week, or weekly IV cisplatin 40 mg/m² during radiation therapy.

The study results were published in the Journal of Clinical Oncology.

The study was prematurely closed after an unplanned interim analysis when 298 patients had been randomly assigned. The cumulative incidence of locoregional failures at 3 years was more than twice as high in the cetuximab group (23%), compared with the cisplatin group (9%; P = .0036). At 3 years, overall survival was higher in the cisplatin (88%) group than in the cetuximab group (78%), but the difference was not significant (P = .086). The cumulative incidence of distant failures did not differ between the treatment groups, and the toxicity burden was similar.

“Concurrent cisplatin led to improved locoregional control and event-free survival with a trend toward improved overall survival. The types of toxicity were different, as would be expected with the different drug mechanisms, but the rate of toxicity was not,” said Dr. Dr. Jhawar. “Interestingly, the benefit of cisplatin seemed to be limited to patients with p16-positive oropharyngeal cancer. There was clinical equipoise in the p16-negative oropharyngeal cancer group and in the non–oropharyngeal cancer group. The numbers were small, but this is intriguing and suggests that there is more work to be done in this group of patients to tease out if we can escalate or use alternative therapy.”

Cisplatin has been repeatedly proven to be superior in selected populations. The next steps, said Dr. Jhawar, include defining “optimal regimens in cisplatin-ineligible populations based on age, performance status, kidney function, hearing loss, neuropathy, and HIV/AIDS; improvements with new targeted therapies and immunotherapies; and deescalation of systemic and/or radiation regimens in the best outcome groups, such as low-risk HPV-positive patients. And we are going to see more personalized medicine with genetic testing of tumors.”

When patients are ineligible for cisplatin, no optimal regimens have been defined as yet. At Ohio State, Dr. Jhawar and colleagues use carboplatin therapy.

For practicing oncologists, Dr. Jhawar said the bottom line is “patients who are eligible should receive concurrent cisplatin therapy for locoregionally advanced head and neck cancer.”

The ARTSCAN III study was funded by the Swedish Cancer Society and the Mrs. Berta Kamprad Cancer Foundation. One of the study’s coauthors reported a leadership role in ScandiDos. The other authors reported they had no conflicts. Dr. Jhawar reported he had no conflicts of interest.




 

Neoadjuvant atezolizumab prior to lung cancer surgery was well tolerated by patients with stage IB-IIIB lung cancer and produced a 21% major pathologic response rate, according to the primary analysis of the Lung Cancer Mutation Consortium (LCMC) 3 study.

Small pilot studies previously suggested that preoperative immune checkpoint inhibitor (ICI) therapy may benefit patients with resectable non–small cell lung cancer (NSCLC).

The LCMC3 study is “unique” because it is the largest monotherapy trial of checkpoint inhibition in resectable NSCLC, and it’s “a landmark study” because it validated results from smaller trials and can serve as a benchmark for future ones, said Jay M. Lee, MD, of the University of California, Los Angeles.

Dr. Lee presented results from LCMC3 at the 2020 World Congress on Lung Cancer (Abstract PS01.05), which was rescheduled for January 2021.

The study included 181 patients, median age 65 years, with stage IB-IIIB NSCLC. The vast majority (90%) of patients were current/former smokers, and two-thirds had a nonsquamous histology. Patients were categorized in the following stages: 17 patients were staged at IB, 20 were IIA, 55 were IIB, 72 were IIIA, and 17 were IIIB.

Patients received 1,200 mg of neoadjuvant atezolizumab intravenously every 3 weeks for two cycles followed by resection between 30 and 50 days from the first cycle. Patients who benefited from the therapy continued adjuvant atezolizumab for 12 months.

The primary endpoint was major pathological response, defined as no more than 10% viable tumor cells at surgery, in patients without epidermal growth factor receptor or anaplastic lymphoma kinase mutations.
 

Results

Following atezolizumab treatment, 43% of patients were down-staged, and 19% were up-staged. Some degree of pathological regression was observed in all but 3 of the 159 patients who underwent resection.

Among the 144 patients included in the efficacy analysis, the major pathological response rate was 21%, with 7% of patients achieving a complete pathological response.

“We demonstrated that more than half of patients resected with a minimally invasive operation. Remarkably, only 15% required thoracotomy. The 92% complete resection rate is comparable, if not superior to, preoperative chemotherapy trials,” Dr. Lee said.

The majority (88%) of patients underwent surgical resection within a 20-day protocol window. The median time from end of neoadjuvant therapy to surgery was 22 days.

“Historically, the neoadjuvant chemotherapy window is much later for surgery, 3 weeks from neoadjuvant therapy, and that can be stretched to up to 56 days,” Dr. Lee said.

In an exploratory analysis, the 1.5-year overall survival rate was 91% for stage I and II disease and 87% for stage III disease. The survival in both cohorts was superior to that expected historically, Dr. Lee noted.

Intraoperative complications were rare (3%). Postoperative adverse reactions correlated with fewer viable tumor cells in the resected specimen.

One patient died following surgery after the first 30 days, which was deemed unrelated to treatment. Another patient died between 30 and 90 days from treatment-related pneumonitis.

“The LCMC3 study successfully met its primary endpoint of achieving major pathological response,” Dr. Lee concluded. “Neoadjuvant atezolizumab monotherapy was well tolerated, and resection was performed with low perioperative morbidity and mortality, usually within a narrow protocol window and with a short time frame from completion of atezolizumab and with a correspondingly high complete resection rate.”

The study’s results suggest that “neoadjuvant atezolizumab monotherapy is effective, well tolerated, and surgically acceptable,” said study discussant Shinichi Toyooka, MD, of Okayama (Japan) University Hospital.

“I would consider single-agent ICI neoadjuvant therapy for patients with early-stage disease and poor performance status, and an ICI plus chemotherapy for more advanced resectable cases, like locally advanced disease,” Dr. Toyooka said.

The LCMC3 study is sponsored by Genentech. Dr. Lee disclosed relationships with Genentech/Roche, AstraZeneca, Bristol-Myers Squibb, Merck, and Novartis. Dr. Toyooka disclosed relationships with AstraZeneca, Chugai, Taiho Pharmaceutical Group, and Ono Pharmaceutical.

Neoadjuvant atezolizumab prior to lung cancer surgery was well tolerated by patients with stage IB-IIIB lung cancer and produced a 21% major pathologic response rate, according to the primary analysis of the Lung Cancer Mutation Consortium (LCMC) 3 study.

Small pilot studies previously suggested that preoperative immune checkpoint inhibitor (ICI) therapy may benefit patients with resectable non–small cell lung cancer (NSCLC).

The LCMC3 study is “unique” because it is the largest monotherapy trial of checkpoint inhibition in resectable NSCLC, and it’s “a landmark study” because it validated results from smaller trials and can serve as a benchmark for future ones, said Jay M. Lee, MD, of the University of California, Los Angeles.

Dr. Lee presented results from LCMC3 at the 2020 World Congress on Lung Cancer (Abstract PS01.05), which was rescheduled for January 2021.

The study included 181 patients, median age 65 years, with stage IB-IIIB NSCLC. The vast majority (90%) of patients were current/former smokers, and two-thirds had a nonsquamous histology. Patients were categorized in the following stages: 17 patients were staged at IB, 20 were IIA, 55 were IIB, 72 were IIIA, and 17 were IIIB.

Patients received 1,200 mg of neoadjuvant atezolizumab intravenously every 3 weeks for two cycles followed by resection between 30 and 50 days from the first cycle. Patients who benefited from the therapy continued adjuvant atezolizumab for 12 months.

The primary endpoint was major pathological response, defined as no more than 10% viable tumor cells at surgery, in patients without epidermal growth factor receptor or anaplastic lymphoma kinase mutations.
 

Results

Following atezolizumab treatment, 43% of patients were down-staged, and 19% were up-staged. Some degree of pathological regression was observed in all but 3 of the 159 patients who underwent resection.

Among the 144 patients included in the efficacy analysis, the major pathological response rate was 21%, with 7% of patients achieving a complete pathological response.

“We demonstrated that more than half of patients resected with a minimally invasive operation. Remarkably, only 15% required thoracotomy. The 92% complete resection rate is comparable, if not superior to, preoperative chemotherapy trials,” Dr. Lee said.

The majority (88%) of patients underwent surgical resection within a 20-day protocol window. The median time from end of neoadjuvant therapy to surgery was 22 days.

“Historically, the neoadjuvant chemotherapy window is much later for surgery, 3 weeks from neoadjuvant therapy, and that can be stretched to up to 56 days,” Dr. Lee said.

In an exploratory analysis, the 1.5-year overall survival rate was 91% for stage I and II disease and 87% for stage III disease. The survival in both cohorts was superior to that expected historically, Dr. Lee noted.

Intraoperative complications were rare (3%). Postoperative adverse reactions correlated with fewer viable tumor cells in the resected specimen.

One patient died following surgery after the first 30 days, which was deemed unrelated to treatment. Another patient died between 30 and 90 days from treatment-related pneumonitis.

“The LCMC3 study successfully met its primary endpoint of achieving major pathological response,” Dr. Lee concluded. “Neoadjuvant atezolizumab monotherapy was well tolerated, and resection was performed with low perioperative morbidity and mortality, usually within a narrow protocol window and with a short time frame from completion of atezolizumab and with a correspondingly high complete resection rate.”

The study’s results suggest that “neoadjuvant atezolizumab monotherapy is effective, well tolerated, and surgically acceptable,” said study discussant Shinichi Toyooka, MD, of Okayama (Japan) University Hospital.

“I would consider single-agent ICI neoadjuvant therapy for patients with early-stage disease and poor performance status, and an ICI plus chemotherapy for more advanced resectable cases, like locally advanced disease,” Dr. Toyooka said.

The LCMC3 study is sponsored by Genentech. Dr. Lee disclosed relationships with Genentech/Roche, AstraZeneca, Bristol-Myers Squibb, Merck, and Novartis. Dr. Toyooka disclosed relationships with AstraZeneca, Chugai, Taiho Pharmaceutical Group, and Ono Pharmaceutical.

Neoadjuvant atezolizumab prior to lung cancer surgery was well tolerated by patients with stage IB-IIIB lung cancer and produced a 21% major pathologic response rate, according to the primary analysis of the Lung Cancer Mutation Consortium (LCMC) 3 study.

Small pilot studies previously suggested that preoperative immune checkpoint inhibitor (ICI) therapy may benefit patients with resectable non–small cell lung cancer (NSCLC).

The LCMC3 study is “unique” because it is the largest monotherapy trial of checkpoint inhibition in resectable NSCLC, and it’s “a landmark study” because it validated results from smaller trials and can serve as a benchmark for future ones, said Jay M. Lee, MD, of the University of California, Los Angeles.

Dr. Lee presented results from LCMC3 at the 2020 World Congress on Lung Cancer (Abstract PS01.05), which was rescheduled for January 2021.

The study included 181 patients, median age 65 years, with stage IB-IIIB NSCLC. The vast majority (90%) of patients were current/former smokers, and two-thirds had a nonsquamous histology. Patients were categorized in the following stages: 17 patients were staged at IB, 20 were IIA, 55 were IIB, 72 were IIIA, and 17 were IIIB.

Patients received 1,200 mg of neoadjuvant atezolizumab intravenously every 3 weeks for two cycles followed by resection between 30 and 50 days from the first cycle. Patients who benefited from the therapy continued adjuvant atezolizumab for 12 months.

The primary endpoint was major pathological response, defined as no more than 10% viable tumor cells at surgery, in patients without epidermal growth factor receptor or anaplastic lymphoma kinase mutations.
 

Results

Following atezolizumab treatment, 43% of patients were down-staged, and 19% were up-staged. Some degree of pathological regression was observed in all but 3 of the 159 patients who underwent resection.

Among the 144 patients included in the efficacy analysis, the major pathological response rate was 21%, with 7% of patients achieving a complete pathological response.

“We demonstrated that more than half of patients resected with a minimally invasive operation. Remarkably, only 15% required thoracotomy. The 92% complete resection rate is comparable, if not superior to, preoperative chemotherapy trials,” Dr. Lee said.

The majority (88%) of patients underwent surgical resection within a 20-day protocol window. The median time from end of neoadjuvant therapy to surgery was 22 days.

“Historically, the neoadjuvant chemotherapy window is much later for surgery, 3 weeks from neoadjuvant therapy, and that can be stretched to up to 56 days,” Dr. Lee said.

In an exploratory analysis, the 1.5-year overall survival rate was 91% for stage I and II disease and 87% for stage III disease. The survival in both cohorts was superior to that expected historically, Dr. Lee noted.

Intraoperative complications were rare (3%). Postoperative adverse reactions correlated with fewer viable tumor cells in the resected specimen.

One patient died following surgery after the first 30 days, which was deemed unrelated to treatment. Another patient died between 30 and 90 days from treatment-related pneumonitis.

“The LCMC3 study successfully met its primary endpoint of achieving major pathological response,” Dr. Lee concluded. “Neoadjuvant atezolizumab monotherapy was well tolerated, and resection was performed with low perioperative morbidity and mortality, usually within a narrow protocol window and with a short time frame from completion of atezolizumab and with a correspondingly high complete resection rate.”

The study’s results suggest that “neoadjuvant atezolizumab monotherapy is effective, well tolerated, and surgically acceptable,” said study discussant Shinichi Toyooka, MD, of Okayama (Japan) University Hospital.

“I would consider single-agent ICI neoadjuvant therapy for patients with early-stage disease and poor performance status, and an ICI plus chemotherapy for more advanced resectable cases, like locally advanced disease,” Dr. Toyooka said.

The LCMC3 study is sponsored by Genentech. Dr. Lee disclosed relationships with Genentech/Roche, AstraZeneca, Bristol-Myers Squibb, Merck, and Novartis. Dr. Toyooka disclosed relationships with AstraZeneca, Chugai, Taiho Pharmaceutical Group, and Ono Pharmaceutical.

The KRAS inhibitor sotorasib provides durable clinical benefit in heavily pretreated patients with non–small cell lung cancer (NSCLC) harboring KRAS p.G12C mutations, results of a phase 2 trial suggest.

“This is a historic milestone in lung cancer therapy. After 4 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,” said Bob T. Li, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Li reported results with sotorasib in NSCLC, from the phase 2 part of the CodeBreaK 100 trial, at the 2020 World Conference on Lung Cancer (Abstract PS01.07), which was rescheduled for January 2021.

“It’s an absolutely remarkable study,” said Dean A. Fennell, MBBS, PhD, of the University of Leicester and University Hospitals of Leicester NHS Trust in the United Kingdom.

“The ‘un-druggability’ of KRAS has been something of a challenge for decades. To see results like this from Dr. Li is absolutely fabulous and will lead to a new stratification option.”
 

Rationale and study details

Dr. Li noted that the KRAS p.G12C mutation is a key oncogenic driver, occurring in about 13% of lung adenocarcinomas.

Sotorasib is a first-in-class, highly selective, irreversible KRASG12C inhibitor. It showed durable clinical benefit in 59 NSCLC patients enrolled in the phase 1 part of the CodeBreaK 100 trial (N Engl J Med 2020;383:1207-17). One-third of the patients had an objective response across all doses tested. The median duration of response was 10.9 months, and the median progression-free survival was 6.3 months.

The phase 2 part of CodeBreaK 100 included 126 patients from 11 countries in North America, Europe, and Asia-Pacific. Their median age was 63.5 years (range, 37-80 years), and 92.9% were current or former smokers.

Patients had locally advanced or metastatic NSCLC and a centrally confirmed KRAS p.G12C mutation. They had progressed after three or fewer prior lines of therapy.

Patients received oral sotorasib at 960 mg daily until disease progression. They were followed for a median of 12.2 months. An independent blinded central review found that 124 patients had at least one measurable lesion at baseline and were therefore evaluable for efficacy.

Phase 2 results

Sotorasib “demonstrated early, deep, and durable responses,” Dr. Li said.

In all, 46 patients had a confirmed response – 3 complete responses and 43 partial responses – for an objective response rate of 37.1%.

The median time to objective response was 1.4 months, the median duration of response was 10 months, and 43% of responders were still on treatment without progression at the data cutoff.

“Tumor response to sotorasib was observed across a range of biomarker subgroups, including patients with negative or low PD-L1 expression level and those with mutant STK11,” Dr. Li said.

The disease control rate was 80.6%, and tumors shrank by an average of about 60%. The median progression-free survival was 6.8 months.

Treatment-related adverse events (TRAEs) were acceptable, with no surprises compared to phase 1 results, Dr. Li said.

TRAEs of any grade occurred in 69.8% of patients and led to discontinuation in 7.1%. TRAEs led to dose modification in 22.2% of patients.

Grade 3 TRAEs were reported in 19.8% of patients, including alanine aminotransferase increase (6.3%), aspartate aminotransferase increase (5.6%), diarrhea (4.0%), and blood alkaline phosphatase increase (0.8%).

“Sotorasib was well tolerated, with no deaths attributed to treatment and low incidence of grade 3 or 4 TRAEs, treatment discontinuation, and dose modification,” Dr. Li said.

A phase 3 trial of sotorasib compared with second-line docetaxel is now enrolling patients.

The phase 1/2 CodeBreaK 100 trial was funded by Amgen. Dr. Li disclosed relationships with Amgen and many other companies. Dr. Fennell disclosed relationships with AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Merck, Roche, Astex Therapeutics, Bayer, Lab21, Atara Biotherapeutics, Boehringer Ingelheim, and Inventiva.

The KRAS inhibitor sotorasib provides durable clinical benefit in heavily pretreated patients with non–small cell lung cancer (NSCLC) harboring KRAS p.G12C mutations, results of a phase 2 trial suggest.

“This is a historic milestone in lung cancer therapy. After 4 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,” said Bob T. Li, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Li reported results with sotorasib in NSCLC, from the phase 2 part of the CodeBreaK 100 trial, at the 2020 World Conference on Lung Cancer (Abstract PS01.07), which was rescheduled for January 2021.

“It’s an absolutely remarkable study,” said Dean A. Fennell, MBBS, PhD, of the University of Leicester and University Hospitals of Leicester NHS Trust in the United Kingdom.

“The ‘un-druggability’ of KRAS has been something of a challenge for decades. To see results like this from Dr. Li is absolutely fabulous and will lead to a new stratification option.”
 

Rationale and study details

Dr. Li noted that the KRAS p.G12C mutation is a key oncogenic driver, occurring in about 13% of lung adenocarcinomas.

Sotorasib is a first-in-class, highly selective, irreversible KRASG12C inhibitor. It showed durable clinical benefit in 59 NSCLC patients enrolled in the phase 1 part of the CodeBreaK 100 trial (N Engl J Med 2020;383:1207-17). One-third of the patients had an objective response across all doses tested. The median duration of response was 10.9 months, and the median progression-free survival was 6.3 months.

The phase 2 part of CodeBreaK 100 included 126 patients from 11 countries in North America, Europe, and Asia-Pacific. Their median age was 63.5 years (range, 37-80 years), and 92.9% were current or former smokers.

Patients had locally advanced or metastatic NSCLC and a centrally confirmed KRAS p.G12C mutation. They had progressed after three or fewer prior lines of therapy.

Patients received oral sotorasib at 960 mg daily until disease progression. They were followed for a median of 12.2 months. An independent blinded central review found that 124 patients had at least one measurable lesion at baseline and were therefore evaluable for efficacy.

Phase 2 results

Sotorasib “demonstrated early, deep, and durable responses,” Dr. Li said.

In all, 46 patients had a confirmed response – 3 complete responses and 43 partial responses – for an objective response rate of 37.1%.

The median time to objective response was 1.4 months, the median duration of response was 10 months, and 43% of responders were still on treatment without progression at the data cutoff.

“Tumor response to sotorasib was observed across a range of biomarker subgroups, including patients with negative or low PD-L1 expression level and those with mutant STK11,” Dr. Li said.

The disease control rate was 80.6%, and tumors shrank by an average of about 60%. The median progression-free survival was 6.8 months.

Treatment-related adverse events (TRAEs) were acceptable, with no surprises compared to phase 1 results, Dr. Li said.

TRAEs of any grade occurred in 69.8% of patients and led to discontinuation in 7.1%. TRAEs led to dose modification in 22.2% of patients.

Grade 3 TRAEs were reported in 19.8% of patients, including alanine aminotransferase increase (6.3%), aspartate aminotransferase increase (5.6%), diarrhea (4.0%), and blood alkaline phosphatase increase (0.8%).

“Sotorasib was well tolerated, with no deaths attributed to treatment and low incidence of grade 3 or 4 TRAEs, treatment discontinuation, and dose modification,” Dr. Li said.

A phase 3 trial of sotorasib compared with second-line docetaxel is now enrolling patients.

The phase 1/2 CodeBreaK 100 trial was funded by Amgen. Dr. Li disclosed relationships with Amgen and many other companies. Dr. Fennell disclosed relationships with AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Merck, Roche, Astex Therapeutics, Bayer, Lab21, Atara Biotherapeutics, Boehringer Ingelheim, and Inventiva.

The KRAS inhibitor sotorasib provides durable clinical benefit in heavily pretreated patients with non–small cell lung cancer (NSCLC) harboring KRAS p.G12C mutations, results of a phase 2 trial suggest.

“This is a historic milestone in lung cancer therapy. After 4 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,” said Bob T. Li, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Li reported results with sotorasib in NSCLC, from the phase 2 part of the CodeBreaK 100 trial, at the 2020 World Conference on Lung Cancer (Abstract PS01.07), which was rescheduled for January 2021.

“It’s an absolutely remarkable study,” said Dean A. Fennell, MBBS, PhD, of the University of Leicester and University Hospitals of Leicester NHS Trust in the United Kingdom.

“The ‘un-druggability’ of KRAS has been something of a challenge for decades. To see results like this from Dr. Li is absolutely fabulous and will lead to a new stratification option.”
 

Rationale and study details

Dr. Li noted that the KRAS p.G12C mutation is a key oncogenic driver, occurring in about 13% of lung adenocarcinomas.

Sotorasib is a first-in-class, highly selective, irreversible KRASG12C inhibitor. It showed durable clinical benefit in 59 NSCLC patients enrolled in the phase 1 part of the CodeBreaK 100 trial (N Engl J Med 2020;383:1207-17). One-third of the patients had an objective response across all doses tested. The median duration of response was 10.9 months, and the median progression-free survival was 6.3 months.

The phase 2 part of CodeBreaK 100 included 126 patients from 11 countries in North America, Europe, and Asia-Pacific. Their median age was 63.5 years (range, 37-80 years), and 92.9% were current or former smokers.

Patients had locally advanced or metastatic NSCLC and a centrally confirmed KRAS p.G12C mutation. They had progressed after three or fewer prior lines of therapy.

Patients received oral sotorasib at 960 mg daily until disease progression. They were followed for a median of 12.2 months. An independent blinded central review found that 124 patients had at least one measurable lesion at baseline and were therefore evaluable for efficacy.

Phase 2 results

Sotorasib “demonstrated early, deep, and durable responses,” Dr. Li said.

In all, 46 patients had a confirmed response – 3 complete responses and 43 partial responses – for an objective response rate of 37.1%.

The median time to objective response was 1.4 months, the median duration of response was 10 months, and 43% of responders were still on treatment without progression at the data cutoff.

“Tumor response to sotorasib was observed across a range of biomarker subgroups, including patients with negative or low PD-L1 expression level and those with mutant STK11,” Dr. Li said.

The disease control rate was 80.6%, and tumors shrank by an average of about 60%. The median progression-free survival was 6.8 months.

Treatment-related adverse events (TRAEs) were acceptable, with no surprises compared to phase 1 results, Dr. Li said.

TRAEs of any grade occurred in 69.8% of patients and led to discontinuation in 7.1%. TRAEs led to dose modification in 22.2% of patients.

Grade 3 TRAEs were reported in 19.8% of patients, including alanine aminotransferase increase (6.3%), aspartate aminotransferase increase (5.6%), diarrhea (4.0%), and blood alkaline phosphatase increase (0.8%).

“Sotorasib was well tolerated, with no deaths attributed to treatment and low incidence of grade 3 or 4 TRAEs, treatment discontinuation, and dose modification,” Dr. Li said.

A phase 3 trial of sotorasib compared with second-line docetaxel is now enrolling patients.

The phase 1/2 CodeBreaK 100 trial was funded by Amgen. Dr. Li disclosed relationships with Amgen and many other companies. Dr. Fennell disclosed relationships with AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Merck, Roche, Astex Therapeutics, Bayer, Lab21, Atara Biotherapeutics, Boehringer Ingelheim, and Inventiva.

A third of patients with COVID-19 and thoracic malignancies die, according to updated results from the TERAVOLT registry.

The risk of death was similar across racial and ethnic groups. Factors associated with an increased risk of death were male sex, older age, worse performance scores, and four or more metastatic sites.

“Death rates remain high at 33%, underscoring the importance of COVID-19 vaccination in patients with thoracic cancers, when available,” said Umit Tapan, MD, of Boston University.

Dr. Tapan presented the TERAVOLT update at the 2020 World Congress on Lung Cancer (Abstract P09.18), which was rescheduled for January 2021.

The TERAVOLT registry is a multicenter, observational study with a cross-sectional component and a longitudinal cohort component.

The registry includes patients who have thoracic cancers – non–small cell lung cancer (NSCLC), small cell lung cancer, mesothelioma, thymic epithelial tumors, and other pulmonary neuroendocrine neoplasms – and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms.

Clinical data were extracted from medical records of consecutive patients from Jan. 1, 2020, and will be collected until the end of pandemic, as declared by the World Health Organization. Data collected include demographics, oncologic history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes.

“The overarching goals of this consortium are to provide data for guidance to oncology professionals on managing patients with thoracic malignancies while understanding the risk factors for morbidity and mortality from this novel virus,” Dr. Tapan said.

Data from TERAVOLT were previously presented at AACR, ASCO, and ESMO last year, as well as published in The Lancet Oncology.

Updated results

Dr. Tapan presented data on 1,011 patients from 120 centers in 19 countries. The patients’ median age was 68 years (range, 28-95 years), and more than half were male (58%). Most patients (72%) were White, 20% were Hispanic/Latino, and 8% were Black/African American.

Most patients had NSCLC (82%), and most had stage IV disease (68%). Patients had received a median of one prior line of therapy.

As in earlier reports of TERAVOLT data, the mortality rate was 33%.

In a multivariate analysis, the following characteristics were associated with an increased risk of death:

• Male sex (odds ratio, 1.4).
• Older age (per 10 years; OR, 1.21).
• Performance score of 1 (OR, 1.73), 2 (OR, 4.74), and 3/4 (OR, 10.7).
• Four or more metastatic sites (OR, 3.05).

The following characteristics were associated with an increased risk of hospitalization in a multivariate analysis:

• Male sex (OR, 1.67).
• Older age (per 10 years; OR, 1.24).
• Performance score of 2 (OR, 4.47) and 3/4 (OR, 9.63).
• Four or more metastatic sites (OR, 4.0).
• Thymic carcinoma (OR, 3.58).
• Receiving radiation (OR, 2.1).

Race and ethnicity did not seem to affect the risk of death or hospitalization, “but we plan to conduct further analysis,” Dr. Tapan said.

Roxana Reyes, MD, of Hospital Clínic de Barcelona, said her hospital sees patients with lung cancer at high risk for COVID-19, but there is no screening program in place.

“We use medical consultations to focus on early diagnosis. We treat COVID-19 complications but lose a lot of patients. There is an opportunity to be found to find these patients sooner,” Dr. Reyes said.

She noted that COVID-19 will likely last a long time, and therefore “we have to protect against it and continue to diagnose lung cancer at earlier stages.”

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. Dr. Tapan has no relevant disclosures. The TERAVOLT registry is funded, in part, by the International Association for the Study of Lung Cancer.

A third of patients with COVID-19 and thoracic malignancies die, according to updated results from the TERAVOLT registry.

The risk of death was similar across racial and ethnic groups. Factors associated with an increased risk of death were male sex, older age, worse performance scores, and four or more metastatic sites.

“Death rates remain high at 33%, underscoring the importance of COVID-19 vaccination in patients with thoracic cancers, when available,” said Umit Tapan, MD, of Boston University.

Dr. Tapan presented the TERAVOLT update at the 2020 World Congress on Lung Cancer (Abstract P09.18), which was rescheduled for January 2021.

The TERAVOLT registry is a multicenter, observational study with a cross-sectional component and a longitudinal cohort component.

The registry includes patients who have thoracic cancers – non–small cell lung cancer (NSCLC), small cell lung cancer, mesothelioma, thymic epithelial tumors, and other pulmonary neuroendocrine neoplasms – and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms.

Clinical data were extracted from medical records of consecutive patients from Jan. 1, 2020, and will be collected until the end of pandemic, as declared by the World Health Organization. Data collected include demographics, oncologic history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes.

“The overarching goals of this consortium are to provide data for guidance to oncology professionals on managing patients with thoracic malignancies while understanding the risk factors for morbidity and mortality from this novel virus,” Dr. Tapan said.

Data from TERAVOLT were previously presented at AACR, ASCO, and ESMO last year, as well as published in The Lancet Oncology.

Updated results

Dr. Tapan presented data on 1,011 patients from 120 centers in 19 countries. The patients’ median age was 68 years (range, 28-95 years), and more than half were male (58%). Most patients (72%) were White, 20% were Hispanic/Latino, and 8% were Black/African American.

Most patients had NSCLC (82%), and most had stage IV disease (68%). Patients had received a median of one prior line of therapy.

As in earlier reports of TERAVOLT data, the mortality rate was 33%.

In a multivariate analysis, the following characteristics were associated with an increased risk of death:

• Male sex (odds ratio, 1.4).
• Older age (per 10 years; OR, 1.21).
• Performance score of 1 (OR, 1.73), 2 (OR, 4.74), and 3/4 (OR, 10.7).
• Four or more metastatic sites (OR, 3.05).

The following characteristics were associated with an increased risk of hospitalization in a multivariate analysis:

• Male sex (OR, 1.67).
• Older age (per 10 years; OR, 1.24).
• Performance score of 2 (OR, 4.47) and 3/4 (OR, 9.63).
• Four or more metastatic sites (OR, 4.0).
• Thymic carcinoma (OR, 3.58).
• Receiving radiation (OR, 2.1).

Race and ethnicity did not seem to affect the risk of death or hospitalization, “but we plan to conduct further analysis,” Dr. Tapan said.

Roxana Reyes, MD, of Hospital Clínic de Barcelona, said her hospital sees patients with lung cancer at high risk for COVID-19, but there is no screening program in place.

“We use medical consultations to focus on early diagnosis. We treat COVID-19 complications but lose a lot of patients. There is an opportunity to be found to find these patients sooner,” Dr. Reyes said.

She noted that COVID-19 will likely last a long time, and therefore “we have to protect against it and continue to diagnose lung cancer at earlier stages.”

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. Dr. Tapan has no relevant disclosures. The TERAVOLT registry is funded, in part, by the International Association for the Study of Lung Cancer.

A third of patients with COVID-19 and thoracic malignancies die, according to updated results from the TERAVOLT registry.

The risk of death was similar across racial and ethnic groups. Factors associated with an increased risk of death were male sex, older age, worse performance scores, and four or more metastatic sites.

“Death rates remain high at 33%, underscoring the importance of COVID-19 vaccination in patients with thoracic cancers, when available,” said Umit Tapan, MD, of Boston University.

Dr. Tapan presented the TERAVOLT update at the 2020 World Congress on Lung Cancer (Abstract P09.18), which was rescheduled for January 2021.

The TERAVOLT registry is a multicenter, observational study with a cross-sectional component and a longitudinal cohort component.

The registry includes patients who have thoracic cancers – non–small cell lung cancer (NSCLC), small cell lung cancer, mesothelioma, thymic epithelial tumors, and other pulmonary neuroendocrine neoplasms – and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms.

Clinical data were extracted from medical records of consecutive patients from Jan. 1, 2020, and will be collected until the end of pandemic, as declared by the World Health Organization. Data collected include demographics, oncologic history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes.

“The overarching goals of this consortium are to provide data for guidance to oncology professionals on managing patients with thoracic malignancies while understanding the risk factors for morbidity and mortality from this novel virus,” Dr. Tapan said.

Data from TERAVOLT were previously presented at AACR, ASCO, and ESMO last year, as well as published in The Lancet Oncology.

Updated results

Dr. Tapan presented data on 1,011 patients from 120 centers in 19 countries. The patients’ median age was 68 years (range, 28-95 years), and more than half were male (58%). Most patients (72%) were White, 20% were Hispanic/Latino, and 8% were Black/African American.

Most patients had NSCLC (82%), and most had stage IV disease (68%). Patients had received a median of one prior line of therapy.

As in earlier reports of TERAVOLT data, the mortality rate was 33%.

In a multivariate analysis, the following characteristics were associated with an increased risk of death:

• Male sex (odds ratio, 1.4).
• Older age (per 10 years; OR, 1.21).
• Performance score of 1 (OR, 1.73), 2 (OR, 4.74), and 3/4 (OR, 10.7).
• Four or more metastatic sites (OR, 3.05).

The following characteristics were associated with an increased risk of hospitalization in a multivariate analysis:

• Male sex (OR, 1.67).
• Older age (per 10 years; OR, 1.24).
• Performance score of 2 (OR, 4.47) and 3/4 (OR, 9.63).
• Four or more metastatic sites (OR, 4.0).
• Thymic carcinoma (OR, 3.58).
• Receiving radiation (OR, 2.1).

Race and ethnicity did not seem to affect the risk of death or hospitalization, “but we plan to conduct further analysis,” Dr. Tapan said.

Roxana Reyes, MD, of Hospital Clínic de Barcelona, said her hospital sees patients with lung cancer at high risk for COVID-19, but there is no screening program in place.

“We use medical consultations to focus on early diagnosis. We treat COVID-19 complications but lose a lot of patients. There is an opportunity to be found to find these patients sooner,” Dr. Reyes said.

She noted that COVID-19 will likely last a long time, and therefore “we have to protect against it and continue to diagnose lung cancer at earlier stages.”

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. Dr. Tapan has no relevant disclosures. The TERAVOLT registry is funded, in part, by the International Association for the Study of Lung Cancer.