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Neoadjuvant immunotherapy for resectable head and neck cancer holds therapeutic benefit
The findings, published Sept. 2 in JAMA Otolaryngology Head & Neck Surgery, are noteworthy because the need for effective treatments in head and neck cancers is critical. It is the sixth most common malignancy in the world largely because of tobacco use and alcohol consumption and long-term outcomes are generally poor.
Currently, the standard care for patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) includes the surgical removal of the tumor followed by chemotherapy and radiotherapy. Despite new treatments, including pembrolizumab and nivolumab for platinum-refractory advanced head and neck squamous cell carcinoma (HNSCC), there are high rates of recurrence.
“The emerging approach of neoadjuvant immunotherapy for solid cancers has set the ground for the integration of programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) inhibitors into the neoadjuvant setting of head and neck squamous cell carcinoma treatment,” wrote the authors of the review which was led by Nidal Muhanna, MD, PhD, Tel Aviv Sourasky Medical Center, Tel Aviv University. “The results [of this analysis] demonstrated favorable outcomes and acceptable tolerance of the administration of neoadjuvant PD-1\PD-L1 inhibitors.”
The analysis included 10 studies
The review included 10 cohort studies and randomized clinical trials of 344 patients who were undergoing treatment for HNSCC between 2015 and 2021. In eight studies, patients received neoadjuvant immunotherapy, and in two studies, patients received combined immunotherapy with neoadjuvant chemotherapy and/or radiotherapy.
The overall pathological response rate was 9.7% (95% confidence interval, 3.1%-18.9%) for primary tumors treated with neoadjuvant immunotherapy or, 2.9% (95% CI, 0%-9.5%) for the pathological complete response rate (with a range of 0%-16.7%).
Treatment with neoadjuvant immunotherapy was ultimately found to be statistically significant (odds ratio, 0.07; 95% CI, 0.03-0.18). Plus, favorable associations for treatment with neoadjuvant immunotherapy were found with nodal pathological complete response. In two studies cited in the analysis, combination treatment with neoadjuvant immunotherapy and chemotherapy and/or radiation before surgery had an overall pathological complete response rate of 53%.
The major pathologic response in which less than 10% of the tumor remained after treatment varied greatly between 2.9% and 31.0% in five studies. The mean major pathologic response in these cases was 9.7%, which suggested a statistically significant association. A major pathologic response for lymph nodes was described in three studies as statistically significant for neoadjuvant immunotherapy.
In terms of adverse events, 8.4% (95% CI, 0.2%-23.2%) of patients were treated for autoimmune colitis, duodenal hemorrhage, mucositis, nausea, vomiting, and syncope.
Combination treatment with neoadjuvant immunotherapy with chemotherapy or radiotherapy continues to be evaluated in clinical trials (NCT03721757, NCT03635164, and NCT03618134). “Whether these combinations have synergistic effects or provide any therapeutic benefit, compared with single-agent therapy is still under investigation. It has been hypothesized that chemotherapy preceding the administration of neoadjuvant immunotherapy may increase antigen presentation by dendritic cells and enhance immune activation against the tumor, which can potentially increase therapeutic efficacy,” the authors wrote.
Other ongoing clinical trials will report survival data in the upcoming years. One of these trials is the IMSTAR-HN, a phase 3 clinical trial assessing neoadjuvant nivolumab with and without ipilimumab as first-line treatment with curative intent for HNSCC. It will report disease-free survival, overall survival, and progression-free survival outcomes.
The authors reported no disclosures.
The findings, published Sept. 2 in JAMA Otolaryngology Head & Neck Surgery, are noteworthy because the need for effective treatments in head and neck cancers is critical. It is the sixth most common malignancy in the world largely because of tobacco use and alcohol consumption and long-term outcomes are generally poor.
Currently, the standard care for patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) includes the surgical removal of the tumor followed by chemotherapy and radiotherapy. Despite new treatments, including pembrolizumab and nivolumab for platinum-refractory advanced head and neck squamous cell carcinoma (HNSCC), there are high rates of recurrence.
“The emerging approach of neoadjuvant immunotherapy for solid cancers has set the ground for the integration of programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) inhibitors into the neoadjuvant setting of head and neck squamous cell carcinoma treatment,” wrote the authors of the review which was led by Nidal Muhanna, MD, PhD, Tel Aviv Sourasky Medical Center, Tel Aviv University. “The results [of this analysis] demonstrated favorable outcomes and acceptable tolerance of the administration of neoadjuvant PD-1\PD-L1 inhibitors.”
The analysis included 10 studies
The review included 10 cohort studies and randomized clinical trials of 344 patients who were undergoing treatment for HNSCC between 2015 and 2021. In eight studies, patients received neoadjuvant immunotherapy, and in two studies, patients received combined immunotherapy with neoadjuvant chemotherapy and/or radiotherapy.
The overall pathological response rate was 9.7% (95% confidence interval, 3.1%-18.9%) for primary tumors treated with neoadjuvant immunotherapy or, 2.9% (95% CI, 0%-9.5%) for the pathological complete response rate (with a range of 0%-16.7%).
Treatment with neoadjuvant immunotherapy was ultimately found to be statistically significant (odds ratio, 0.07; 95% CI, 0.03-0.18). Plus, favorable associations for treatment with neoadjuvant immunotherapy were found with nodal pathological complete response. In two studies cited in the analysis, combination treatment with neoadjuvant immunotherapy and chemotherapy and/or radiation before surgery had an overall pathological complete response rate of 53%.
The major pathologic response in which less than 10% of the tumor remained after treatment varied greatly between 2.9% and 31.0% in five studies. The mean major pathologic response in these cases was 9.7%, which suggested a statistically significant association. A major pathologic response for lymph nodes was described in three studies as statistically significant for neoadjuvant immunotherapy.
In terms of adverse events, 8.4% (95% CI, 0.2%-23.2%) of patients were treated for autoimmune colitis, duodenal hemorrhage, mucositis, nausea, vomiting, and syncope.
Combination treatment with neoadjuvant immunotherapy with chemotherapy or radiotherapy continues to be evaluated in clinical trials (NCT03721757, NCT03635164, and NCT03618134). “Whether these combinations have synergistic effects or provide any therapeutic benefit, compared with single-agent therapy is still under investigation. It has been hypothesized that chemotherapy preceding the administration of neoadjuvant immunotherapy may increase antigen presentation by dendritic cells and enhance immune activation against the tumor, which can potentially increase therapeutic efficacy,” the authors wrote.
Other ongoing clinical trials will report survival data in the upcoming years. One of these trials is the IMSTAR-HN, a phase 3 clinical trial assessing neoadjuvant nivolumab with and without ipilimumab as first-line treatment with curative intent for HNSCC. It will report disease-free survival, overall survival, and progression-free survival outcomes.
The authors reported no disclosures.
The findings, published Sept. 2 in JAMA Otolaryngology Head & Neck Surgery, are noteworthy because the need for effective treatments in head and neck cancers is critical. It is the sixth most common malignancy in the world largely because of tobacco use and alcohol consumption and long-term outcomes are generally poor.
Currently, the standard care for patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) includes the surgical removal of the tumor followed by chemotherapy and radiotherapy. Despite new treatments, including pembrolizumab and nivolumab for platinum-refractory advanced head and neck squamous cell carcinoma (HNSCC), there are high rates of recurrence.
“The emerging approach of neoadjuvant immunotherapy for solid cancers has set the ground for the integration of programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) inhibitors into the neoadjuvant setting of head and neck squamous cell carcinoma treatment,” wrote the authors of the review which was led by Nidal Muhanna, MD, PhD, Tel Aviv Sourasky Medical Center, Tel Aviv University. “The results [of this analysis] demonstrated favorable outcomes and acceptable tolerance of the administration of neoadjuvant PD-1\PD-L1 inhibitors.”
The analysis included 10 studies
The review included 10 cohort studies and randomized clinical trials of 344 patients who were undergoing treatment for HNSCC between 2015 and 2021. In eight studies, patients received neoadjuvant immunotherapy, and in two studies, patients received combined immunotherapy with neoadjuvant chemotherapy and/or radiotherapy.
The overall pathological response rate was 9.7% (95% confidence interval, 3.1%-18.9%) for primary tumors treated with neoadjuvant immunotherapy or, 2.9% (95% CI, 0%-9.5%) for the pathological complete response rate (with a range of 0%-16.7%).
Treatment with neoadjuvant immunotherapy was ultimately found to be statistically significant (odds ratio, 0.07; 95% CI, 0.03-0.18). Plus, favorable associations for treatment with neoadjuvant immunotherapy were found with nodal pathological complete response. In two studies cited in the analysis, combination treatment with neoadjuvant immunotherapy and chemotherapy and/or radiation before surgery had an overall pathological complete response rate of 53%.
The major pathologic response in which less than 10% of the tumor remained after treatment varied greatly between 2.9% and 31.0% in five studies. The mean major pathologic response in these cases was 9.7%, which suggested a statistically significant association. A major pathologic response for lymph nodes was described in three studies as statistically significant for neoadjuvant immunotherapy.
In terms of adverse events, 8.4% (95% CI, 0.2%-23.2%) of patients were treated for autoimmune colitis, duodenal hemorrhage, mucositis, nausea, vomiting, and syncope.
Combination treatment with neoadjuvant immunotherapy with chemotherapy or radiotherapy continues to be evaluated in clinical trials (NCT03721757, NCT03635164, and NCT03618134). “Whether these combinations have synergistic effects or provide any therapeutic benefit, compared with single-agent therapy is still under investigation. It has been hypothesized that chemotherapy preceding the administration of neoadjuvant immunotherapy may increase antigen presentation by dendritic cells and enhance immune activation against the tumor, which can potentially increase therapeutic efficacy,” the authors wrote.
Other ongoing clinical trials will report survival data in the upcoming years. One of these trials is the IMSTAR-HN, a phase 3 clinical trial assessing neoadjuvant nivolumab with and without ipilimumab as first-line treatment with curative intent for HNSCC. It will report disease-free survival, overall survival, and progression-free survival outcomes.
The authors reported no disclosures.
FROM THE JOURNALS
Most community-based oncologists skip biomarker testing
A recent survey shows that fewer than half of community oncologists use biomarker testing to guide patient discussions about treatment, which compares with 73% of academic clinicians.
The findings, reported at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021, highlight the potential for unequal application of the latest advances in cancer genomics and targeted therapies throughout the health care system, which could worsen existing disparities in underserved populations, according to Leigh Boehmer, PharmD, medical director for the Association of Community Cancer Centers, Rockville, Md.
The survey – a mixed-methods approach for assessing practice patterns, attitudes, barriers, and resource needs related to biomarker testing among clinicians – was developed by the ACCC in partnership with the LUNGevity Foundation and administered to clinicians caring for patients with non–small cell lung cancer who are uninsured or covered by Medicaid.
Of 99 respondents, more than 85% were physicians and 68% worked in a community setting. Only 40% indicated they were very familiar or extremely familiar with 2018 Molecular Testing Guidelines for Lung Cancer from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.
Clinicians were most confident about selecting appropriate tests to use, interpreting test results, and prognosticating based on test results, with 77%, 74%, and 74%, respectively, saying they are very confident or extremely confident in those areas. They were less confident about determining when to order testing and in coordinating care across the multidisciplinary team, with 59% and 64%, respectively, saying they were very confident or extremely confident in those areas, Dr. Boehmer reported at the conference.
The shortcomings with respect to communication across teams were echoed in two focus groups convened to further validate the survey results, he noted.
As for the reasons why clinicians ordered biomarker testing, 88% and 82% of community and academic clinicians, respectively, said they did so to help make targeted treatment decisions.
“Only 48% of community clinicians indicated that they use biomarker testing to guide patient discussions, compared to 73% of academic clinicians,” he said. “That finding was considered statistically significant.”
With respect to decision-making about biomarker testing, 41% said they prefer to share the responsibility with patients, whereas 52% said they prefer to make the final decision.
“Shedding further light on this situation, focus group participants expressed that patients lacked comprehension and interest about what testing entails and what testing means for their treatment options,” Dr. Boehmer noted.
In order to make more informed decisions about biomarker testing, respondents said they need more information on financial resources for patient assistance (26%) and education around both published guidelines and practical implications of the clinical data (21%).
When asked about patients’ information needs, 23% said their patients need psychosocial support, 22% said they need financial assistance, and 9% said their patients have no additional resource needs.
However, only 27% said they provide patients with resources related to psychosocial support services, and only 44% share financial assistance information, he said.
Further, the fact that 9% said their patients need no additional resources represents “a disconnect” from the findings of the survey and focus groups, he added.
“We believe that this study identifies key areas of ongoing clinician need related to biomarker testing, including things like increased guideline familiarity, practical applications of guideline-concordant testing, and … how to optimally coordinate multidisciplinary care delivery,” Dr. Boehmer said. “Professional organizations … in partnership with patient advocacy organizations or groups should focus on developing those patient education materials … and tools for improving patient-clinician discussions about biomarker testing.”
The ACCC will be working with the LUNGevity Foundation and the Center for Business Models in Healthcare to develop an intervention to ensure that such discussions are “easily integrated into the care process for every patient,” he noted.
Such efforts are important for ensuring that clinicians are informed about the value of biomarker testing and about guidelines for testing so that patients receive the best possible care, said invited discussant Joshua Sabari, MD, of New York University Langone Health’s Perlmutter Cancer Center.
“I know that, in clinic, when meeting a new patient with non–small cell lung cancer, it’s critical to understand the driver alteration, not only for prognosis, but also for goals-of-care discussion, as well as potential treatment option,” Dr. Sabari said.
Dr. Boehmer reported consulting for Pfizer. Dr. Sabari reported consulting and advisory board membership for multiple pharmaceutical companies.
A recent survey shows that fewer than half of community oncologists use biomarker testing to guide patient discussions about treatment, which compares with 73% of academic clinicians.
The findings, reported at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021, highlight the potential for unequal application of the latest advances in cancer genomics and targeted therapies throughout the health care system, which could worsen existing disparities in underserved populations, according to Leigh Boehmer, PharmD, medical director for the Association of Community Cancer Centers, Rockville, Md.
The survey – a mixed-methods approach for assessing practice patterns, attitudes, barriers, and resource needs related to biomarker testing among clinicians – was developed by the ACCC in partnership with the LUNGevity Foundation and administered to clinicians caring for patients with non–small cell lung cancer who are uninsured or covered by Medicaid.
Of 99 respondents, more than 85% were physicians and 68% worked in a community setting. Only 40% indicated they were very familiar or extremely familiar with 2018 Molecular Testing Guidelines for Lung Cancer from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.
Clinicians were most confident about selecting appropriate tests to use, interpreting test results, and prognosticating based on test results, with 77%, 74%, and 74%, respectively, saying they are very confident or extremely confident in those areas. They were less confident about determining when to order testing and in coordinating care across the multidisciplinary team, with 59% and 64%, respectively, saying they were very confident or extremely confident in those areas, Dr. Boehmer reported at the conference.
The shortcomings with respect to communication across teams were echoed in two focus groups convened to further validate the survey results, he noted.
As for the reasons why clinicians ordered biomarker testing, 88% and 82% of community and academic clinicians, respectively, said they did so to help make targeted treatment decisions.
“Only 48% of community clinicians indicated that they use biomarker testing to guide patient discussions, compared to 73% of academic clinicians,” he said. “That finding was considered statistically significant.”
With respect to decision-making about biomarker testing, 41% said they prefer to share the responsibility with patients, whereas 52% said they prefer to make the final decision.
“Shedding further light on this situation, focus group participants expressed that patients lacked comprehension and interest about what testing entails and what testing means for their treatment options,” Dr. Boehmer noted.
In order to make more informed decisions about biomarker testing, respondents said they need more information on financial resources for patient assistance (26%) and education around both published guidelines and practical implications of the clinical data (21%).
When asked about patients’ information needs, 23% said their patients need psychosocial support, 22% said they need financial assistance, and 9% said their patients have no additional resource needs.
However, only 27% said they provide patients with resources related to psychosocial support services, and only 44% share financial assistance information, he said.
Further, the fact that 9% said their patients need no additional resources represents “a disconnect” from the findings of the survey and focus groups, he added.
“We believe that this study identifies key areas of ongoing clinician need related to biomarker testing, including things like increased guideline familiarity, practical applications of guideline-concordant testing, and … how to optimally coordinate multidisciplinary care delivery,” Dr. Boehmer said. “Professional organizations … in partnership with patient advocacy organizations or groups should focus on developing those patient education materials … and tools for improving patient-clinician discussions about biomarker testing.”
The ACCC will be working with the LUNGevity Foundation and the Center for Business Models in Healthcare to develop an intervention to ensure that such discussions are “easily integrated into the care process for every patient,” he noted.
Such efforts are important for ensuring that clinicians are informed about the value of biomarker testing and about guidelines for testing so that patients receive the best possible care, said invited discussant Joshua Sabari, MD, of New York University Langone Health’s Perlmutter Cancer Center.
“I know that, in clinic, when meeting a new patient with non–small cell lung cancer, it’s critical to understand the driver alteration, not only for prognosis, but also for goals-of-care discussion, as well as potential treatment option,” Dr. Sabari said.
Dr. Boehmer reported consulting for Pfizer. Dr. Sabari reported consulting and advisory board membership for multiple pharmaceutical companies.
A recent survey shows that fewer than half of community oncologists use biomarker testing to guide patient discussions about treatment, which compares with 73% of academic clinicians.
The findings, reported at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021, highlight the potential for unequal application of the latest advances in cancer genomics and targeted therapies throughout the health care system, which could worsen existing disparities in underserved populations, according to Leigh Boehmer, PharmD, medical director for the Association of Community Cancer Centers, Rockville, Md.
The survey – a mixed-methods approach for assessing practice patterns, attitudes, barriers, and resource needs related to biomarker testing among clinicians – was developed by the ACCC in partnership with the LUNGevity Foundation and administered to clinicians caring for patients with non–small cell lung cancer who are uninsured or covered by Medicaid.
Of 99 respondents, more than 85% were physicians and 68% worked in a community setting. Only 40% indicated they were very familiar or extremely familiar with 2018 Molecular Testing Guidelines for Lung Cancer from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.
Clinicians were most confident about selecting appropriate tests to use, interpreting test results, and prognosticating based on test results, with 77%, 74%, and 74%, respectively, saying they are very confident or extremely confident in those areas. They were less confident about determining when to order testing and in coordinating care across the multidisciplinary team, with 59% and 64%, respectively, saying they were very confident or extremely confident in those areas, Dr. Boehmer reported at the conference.
The shortcomings with respect to communication across teams were echoed in two focus groups convened to further validate the survey results, he noted.
As for the reasons why clinicians ordered biomarker testing, 88% and 82% of community and academic clinicians, respectively, said they did so to help make targeted treatment decisions.
“Only 48% of community clinicians indicated that they use biomarker testing to guide patient discussions, compared to 73% of academic clinicians,” he said. “That finding was considered statistically significant.”
With respect to decision-making about biomarker testing, 41% said they prefer to share the responsibility with patients, whereas 52% said they prefer to make the final decision.
“Shedding further light on this situation, focus group participants expressed that patients lacked comprehension and interest about what testing entails and what testing means for their treatment options,” Dr. Boehmer noted.
In order to make more informed decisions about biomarker testing, respondents said they need more information on financial resources for patient assistance (26%) and education around both published guidelines and practical implications of the clinical data (21%).
When asked about patients’ information needs, 23% said their patients need psychosocial support, 22% said they need financial assistance, and 9% said their patients have no additional resource needs.
However, only 27% said they provide patients with resources related to psychosocial support services, and only 44% share financial assistance information, he said.
Further, the fact that 9% said their patients need no additional resources represents “a disconnect” from the findings of the survey and focus groups, he added.
“We believe that this study identifies key areas of ongoing clinician need related to biomarker testing, including things like increased guideline familiarity, practical applications of guideline-concordant testing, and … how to optimally coordinate multidisciplinary care delivery,” Dr. Boehmer said. “Professional organizations … in partnership with patient advocacy organizations or groups should focus on developing those patient education materials … and tools for improving patient-clinician discussions about biomarker testing.”
The ACCC will be working with the LUNGevity Foundation and the Center for Business Models in Healthcare to develop an intervention to ensure that such discussions are “easily integrated into the care process for every patient,” he noted.
Such efforts are important for ensuring that clinicians are informed about the value of biomarker testing and about guidelines for testing so that patients receive the best possible care, said invited discussant Joshua Sabari, MD, of New York University Langone Health’s Perlmutter Cancer Center.
“I know that, in clinic, when meeting a new patient with non–small cell lung cancer, it’s critical to understand the driver alteration, not only for prognosis, but also for goals-of-care discussion, as well as potential treatment option,” Dr. Sabari said.
Dr. Boehmer reported consulting for Pfizer. Dr. Sabari reported consulting and advisory board membership for multiple pharmaceutical companies.
REPORTING FROM WCLC 2020
Combo treatment for NSCLC with brain metastases extends survival by two years for some
The trial is noteworthy because to date, few patients with nonsquamous NSCLC and untreated asymptomatic brain metastases (or those treated with corticosteroids), were ever included in clinical trials that examine the efficacy and safety of chemotherapy and immunotherapy together as first-line treatment, said Ernest Nadal, MD, PhD, of the University of Barcelona Catalan Institute of Oncology at L’Hospitalet de Llobregat. He and his colleagues presented their findings at the meeting, which was organized by the International Association for the Study of Lung Cancer (IASLC).
With only 40 patients, the clinical trial was small, but the safety profile of atezolizumab combined with carboplatin and pemetrexed was favorable in patients with untreated brain metastases and those receiving corticosteroids (dexamethasone of 4 mg once a day or less).
At a median follow-up of 17.3 months, median intracranial and systemic progression-free survival – the co-primary study endpoints, along with safety – were 6.9 months and 8.9 months in 40 patients treated with the immune checkpoint inhibitor and chemotherapy combination, and the 18-month progression-free survival rates were 10.4% and 24.9%, respectively, Dr. Nadal said.
Secondary study endpoints included response rate and overall survival rate. The overall response rate was 40% at 12 weeks; 19 patients (47.5%) had stable disease in the central nervous system, and 19 (47.5%) had a systemic response. The median overall survival was 13.6 months, and 2-year overall survival was 32%.
“The 12-week progression-free survival rate was 60%, [which was] above the expected rate of 50%, and the grade 2-4 toxicity rate was 27.5%, [which was] below the threshold of 35%,” Dr. Nadal said.
Four patients achieved complete response in the brain, and four patients had discordance between systemic and central nervous system response: two with progressive disease in the body and stable disease in the brain, and two with progressive disease in the brain and stable disease in the body.
Study subjects were chemotherapy-naive patients with stage IV non-squamous NSCLC without estimated glomerular filtration rate (EGFR) or anaplastic lymphoma kinase (ALK) genetic alterations and with untreated brain metastases. They were enrolled from 11 clinical sites and treated with carboplatin (5 AUCs) and pemetrexed (500 mg/m2) plus atezolizumab (1,200 mg) every 3 weeks for four to six cycles, followed by maintenance with pemetrexed plus atezolizumab for 2 years or until disease progression or unacceptable toxicity.
Grade 3 treatment-related adverse events occurring in at least 5% of patients were anemia (eight patients), back pain (four patients), thrombocytopenia (two patients) and dyspnea, pneumonitis, and elevated alanine transaminase (one patient each). Grade 4 treatment-related adverse events occurred in three patients and included thrombocytopenia, neutropenia, and hallucinations.
“Brain metastases are the most frequent cancer-related neurological complication and have a major impact on the neurocognitive function, quality of life, and the patient’s prognosis,” Dr. Nadal said, adding that local therapy could add toxicity and delay systemic treatment.
The progression-free survival findings in this study are similar to those reported in the KEYNOTE-189 clinical trial in patients with brain metastases, which showed improved outcomes with pembrolizumab plus chemotherapy in patients with previously untreated metastatic nonsquamous NSCLC, Dr. Nadal said.
The safety profile was also favorable – even in the 17 patients receiving corticosteroids at baseline.
“This combination can result in clinical benefit in terms of overall survival in this population “Correlative studies with brain imaging and blood samples are currently ongoing,” he said.
Charu Aggarwal, MD, MPH, an oncologist with Penn Medicine who specializes in lung cancer, said the findings help address how patients with untreated, asymptomatic brain metastases should be treated.
Taken together with findings from other prospective and retrospective trials in this population, the outcomes demonstrate that “in patients with asymptomatic brain metastases, upfront immunochemotherapy is associated with intracranial response rates,” she said. Patients with asymptomatic brain metastases can be safely treated with chemoimmunotherapy, but “proper patient selection is going to be key.”
Unanswered questions from this study include the size of brain metastases at trial enrollment, whether programmed death-ligand 1 status matters, and whether there is an optimal dose of steroids that should be mandated for inclusion into trials, Dr. Aggarwal added, noting that several trials enrolling patients with lung cancer are seeking to answer these questions.
Dr. Nadal reported receiving research support, speaker bureau fees, and/or honoraria from multiple pharmaceutical companies. Dr. Aggarwal reported serving on an advisory board for multiple pharmaceutical companies. She also reported clinical trial funding to her institution from multiple companies.
The trial is noteworthy because to date, few patients with nonsquamous NSCLC and untreated asymptomatic brain metastases (or those treated with corticosteroids), were ever included in clinical trials that examine the efficacy and safety of chemotherapy and immunotherapy together as first-line treatment, said Ernest Nadal, MD, PhD, of the University of Barcelona Catalan Institute of Oncology at L’Hospitalet de Llobregat. He and his colleagues presented their findings at the meeting, which was organized by the International Association for the Study of Lung Cancer (IASLC).
With only 40 patients, the clinical trial was small, but the safety profile of atezolizumab combined with carboplatin and pemetrexed was favorable in patients with untreated brain metastases and those receiving corticosteroids (dexamethasone of 4 mg once a day or less).
At a median follow-up of 17.3 months, median intracranial and systemic progression-free survival – the co-primary study endpoints, along with safety – were 6.9 months and 8.9 months in 40 patients treated with the immune checkpoint inhibitor and chemotherapy combination, and the 18-month progression-free survival rates were 10.4% and 24.9%, respectively, Dr. Nadal said.
Secondary study endpoints included response rate and overall survival rate. The overall response rate was 40% at 12 weeks; 19 patients (47.5%) had stable disease in the central nervous system, and 19 (47.5%) had a systemic response. The median overall survival was 13.6 months, and 2-year overall survival was 32%.
“The 12-week progression-free survival rate was 60%, [which was] above the expected rate of 50%, and the grade 2-4 toxicity rate was 27.5%, [which was] below the threshold of 35%,” Dr. Nadal said.
Four patients achieved complete response in the brain, and four patients had discordance between systemic and central nervous system response: two with progressive disease in the body and stable disease in the brain, and two with progressive disease in the brain and stable disease in the body.
Study subjects were chemotherapy-naive patients with stage IV non-squamous NSCLC without estimated glomerular filtration rate (EGFR) or anaplastic lymphoma kinase (ALK) genetic alterations and with untreated brain metastases. They were enrolled from 11 clinical sites and treated with carboplatin (5 AUCs) and pemetrexed (500 mg/m2) plus atezolizumab (1,200 mg) every 3 weeks for four to six cycles, followed by maintenance with pemetrexed plus atezolizumab for 2 years or until disease progression or unacceptable toxicity.
Grade 3 treatment-related adverse events occurring in at least 5% of patients were anemia (eight patients), back pain (four patients), thrombocytopenia (two patients) and dyspnea, pneumonitis, and elevated alanine transaminase (one patient each). Grade 4 treatment-related adverse events occurred in three patients and included thrombocytopenia, neutropenia, and hallucinations.
“Brain metastases are the most frequent cancer-related neurological complication and have a major impact on the neurocognitive function, quality of life, and the patient’s prognosis,” Dr. Nadal said, adding that local therapy could add toxicity and delay systemic treatment.
The progression-free survival findings in this study are similar to those reported in the KEYNOTE-189 clinical trial in patients with brain metastases, which showed improved outcomes with pembrolizumab plus chemotherapy in patients with previously untreated metastatic nonsquamous NSCLC, Dr. Nadal said.
The safety profile was also favorable – even in the 17 patients receiving corticosteroids at baseline.
“This combination can result in clinical benefit in terms of overall survival in this population “Correlative studies with brain imaging and blood samples are currently ongoing,” he said.
Charu Aggarwal, MD, MPH, an oncologist with Penn Medicine who specializes in lung cancer, said the findings help address how patients with untreated, asymptomatic brain metastases should be treated.
Taken together with findings from other prospective and retrospective trials in this population, the outcomes demonstrate that “in patients with asymptomatic brain metastases, upfront immunochemotherapy is associated with intracranial response rates,” she said. Patients with asymptomatic brain metastases can be safely treated with chemoimmunotherapy, but “proper patient selection is going to be key.”
Unanswered questions from this study include the size of brain metastases at trial enrollment, whether programmed death-ligand 1 status matters, and whether there is an optimal dose of steroids that should be mandated for inclusion into trials, Dr. Aggarwal added, noting that several trials enrolling patients with lung cancer are seeking to answer these questions.
Dr. Nadal reported receiving research support, speaker bureau fees, and/or honoraria from multiple pharmaceutical companies. Dr. Aggarwal reported serving on an advisory board for multiple pharmaceutical companies. She also reported clinical trial funding to her institution from multiple companies.
The trial is noteworthy because to date, few patients with nonsquamous NSCLC and untreated asymptomatic brain metastases (or those treated with corticosteroids), were ever included in clinical trials that examine the efficacy and safety of chemotherapy and immunotherapy together as first-line treatment, said Ernest Nadal, MD, PhD, of the University of Barcelona Catalan Institute of Oncology at L’Hospitalet de Llobregat. He and his colleagues presented their findings at the meeting, which was organized by the International Association for the Study of Lung Cancer (IASLC).
With only 40 patients, the clinical trial was small, but the safety profile of atezolizumab combined with carboplatin and pemetrexed was favorable in patients with untreated brain metastases and those receiving corticosteroids (dexamethasone of 4 mg once a day or less).
At a median follow-up of 17.3 months, median intracranial and systemic progression-free survival – the co-primary study endpoints, along with safety – were 6.9 months and 8.9 months in 40 patients treated with the immune checkpoint inhibitor and chemotherapy combination, and the 18-month progression-free survival rates were 10.4% and 24.9%, respectively, Dr. Nadal said.
Secondary study endpoints included response rate and overall survival rate. The overall response rate was 40% at 12 weeks; 19 patients (47.5%) had stable disease in the central nervous system, and 19 (47.5%) had a systemic response. The median overall survival was 13.6 months, and 2-year overall survival was 32%.
“The 12-week progression-free survival rate was 60%, [which was] above the expected rate of 50%, and the grade 2-4 toxicity rate was 27.5%, [which was] below the threshold of 35%,” Dr. Nadal said.
Four patients achieved complete response in the brain, and four patients had discordance between systemic and central nervous system response: two with progressive disease in the body and stable disease in the brain, and two with progressive disease in the brain and stable disease in the body.
Study subjects were chemotherapy-naive patients with stage IV non-squamous NSCLC without estimated glomerular filtration rate (EGFR) or anaplastic lymphoma kinase (ALK) genetic alterations and with untreated brain metastases. They were enrolled from 11 clinical sites and treated with carboplatin (5 AUCs) and pemetrexed (500 mg/m2) plus atezolizumab (1,200 mg) every 3 weeks for four to six cycles, followed by maintenance with pemetrexed plus atezolizumab for 2 years or until disease progression or unacceptable toxicity.
Grade 3 treatment-related adverse events occurring in at least 5% of patients were anemia (eight patients), back pain (four patients), thrombocytopenia (two patients) and dyspnea, pneumonitis, and elevated alanine transaminase (one patient each). Grade 4 treatment-related adverse events occurred in three patients and included thrombocytopenia, neutropenia, and hallucinations.
“Brain metastases are the most frequent cancer-related neurological complication and have a major impact on the neurocognitive function, quality of life, and the patient’s prognosis,” Dr. Nadal said, adding that local therapy could add toxicity and delay systemic treatment.
The progression-free survival findings in this study are similar to those reported in the KEYNOTE-189 clinical trial in patients with brain metastases, which showed improved outcomes with pembrolizumab plus chemotherapy in patients with previously untreated metastatic nonsquamous NSCLC, Dr. Nadal said.
The safety profile was also favorable – even in the 17 patients receiving corticosteroids at baseline.
“This combination can result in clinical benefit in terms of overall survival in this population “Correlative studies with brain imaging and blood samples are currently ongoing,” he said.
Charu Aggarwal, MD, MPH, an oncologist with Penn Medicine who specializes in lung cancer, said the findings help address how patients with untreated, asymptomatic brain metastases should be treated.
Taken together with findings from other prospective and retrospective trials in this population, the outcomes demonstrate that “in patients with asymptomatic brain metastases, upfront immunochemotherapy is associated with intracranial response rates,” she said. Patients with asymptomatic brain metastases can be safely treated with chemoimmunotherapy, but “proper patient selection is going to be key.”
Unanswered questions from this study include the size of brain metastases at trial enrollment, whether programmed death-ligand 1 status matters, and whether there is an optimal dose of steroids that should be mandated for inclusion into trials, Dr. Aggarwal added, noting that several trials enrolling patients with lung cancer are seeking to answer these questions.
Dr. Nadal reported receiving research support, speaker bureau fees, and/or honoraria from multiple pharmaceutical companies. Dr. Aggarwal reported serving on an advisory board for multiple pharmaceutical companies. She also reported clinical trial funding to her institution from multiple companies.
REPORTING FROM WCLC 2021
Molecular ‘theranostics’ could guide treatment in thyroid cancer
The statement was issued as ever more data on molecular markers help launch a “new paradigm” in the approach to thyroid cancer, while driving ongoing debate over how they will feed into the use of RAI, first author Seza A. Gulec, MD, of Herbert Wertheim College of Medicine, Florida International University, Miami, said in an interview.
“The controversy over the appropriate use of RAI in thyroid cancer goes back 70 years, as we’ve been long using it based on the assumption that the majority of high-risk tumors respond to RAI,” he explained.
“But the new paradigm calls for identifying, through molecular analysis, the cancers that have the ability to respond to RAI and/or those that could have the response to RAI enhanced through pretreatment.”
In the statement, published in Thyroid, the working group for the three societies describes their agreement on key issues in three broad areas of RAI use: RAI in perioperative risk stratification, the role of RAI imaging in initial staging, and the need to refine understanding of markers of response to RAI therapy.
Avoid unnecessary treatment
The working group underscores the value of the traditional risk stratification and staging models for thyroid cancer – the American Joint Committee on Cancer eighth edition staging rules and ATA risk stratification system – in the immediate perioperative period, which is well established.
The group supports the inclusion of secondary prognostic factors, specifically molecular markers, in risk stratification in the perioperative period, citing their therapeutic and diagnostic (or theranostic) value in improving individualized treatment decisions.
Molecular theranostics comprise molecular cytology, molecular pathology, and molecular imaging.
“Traditional risk stratification systems can be further refined by ... judicious incorporation of molecular theranostics in the primary framework to guide initial patient management decisions,” the authors wrote.
Dr. Gulec said the inclusion of molecular analysis in risk stratification in particular offers the potential to avoid unnecessary treatment in people who can be identified as likely nonresponders.
“The bottom line is that we need to know more about the cancer before we make decisions on how to tackle it,” he said in an interview.
“For the thyroid cancer to respond to RAI, it has to have an intact system to handle the treatment, and the fact is that most high-risk patients have a molecular profile that does not allow them to respond to RAI or to benefit from total thyroidectomy,” Dr. Gulec explained.
However, the ability to perform a complete genomic analysis with advanced molecular sequencing and identify those patients is radically changing things, he concluded.
Dr. Gulec has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The statement was issued as ever more data on molecular markers help launch a “new paradigm” in the approach to thyroid cancer, while driving ongoing debate over how they will feed into the use of RAI, first author Seza A. Gulec, MD, of Herbert Wertheim College of Medicine, Florida International University, Miami, said in an interview.
“The controversy over the appropriate use of RAI in thyroid cancer goes back 70 years, as we’ve been long using it based on the assumption that the majority of high-risk tumors respond to RAI,” he explained.
“But the new paradigm calls for identifying, through molecular analysis, the cancers that have the ability to respond to RAI and/or those that could have the response to RAI enhanced through pretreatment.”
In the statement, published in Thyroid, the working group for the three societies describes their agreement on key issues in three broad areas of RAI use: RAI in perioperative risk stratification, the role of RAI imaging in initial staging, and the need to refine understanding of markers of response to RAI therapy.
Avoid unnecessary treatment
The working group underscores the value of the traditional risk stratification and staging models for thyroid cancer – the American Joint Committee on Cancer eighth edition staging rules and ATA risk stratification system – in the immediate perioperative period, which is well established.
The group supports the inclusion of secondary prognostic factors, specifically molecular markers, in risk stratification in the perioperative period, citing their therapeutic and diagnostic (or theranostic) value in improving individualized treatment decisions.
Molecular theranostics comprise molecular cytology, molecular pathology, and molecular imaging.
“Traditional risk stratification systems can be further refined by ... judicious incorporation of molecular theranostics in the primary framework to guide initial patient management decisions,” the authors wrote.
Dr. Gulec said the inclusion of molecular analysis in risk stratification in particular offers the potential to avoid unnecessary treatment in people who can be identified as likely nonresponders.
“The bottom line is that we need to know more about the cancer before we make decisions on how to tackle it,” he said in an interview.
“For the thyroid cancer to respond to RAI, it has to have an intact system to handle the treatment, and the fact is that most high-risk patients have a molecular profile that does not allow them to respond to RAI or to benefit from total thyroidectomy,” Dr. Gulec explained.
However, the ability to perform a complete genomic analysis with advanced molecular sequencing and identify those patients is radically changing things, he concluded.
Dr. Gulec has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The statement was issued as ever more data on molecular markers help launch a “new paradigm” in the approach to thyroid cancer, while driving ongoing debate over how they will feed into the use of RAI, first author Seza A. Gulec, MD, of Herbert Wertheim College of Medicine, Florida International University, Miami, said in an interview.
“The controversy over the appropriate use of RAI in thyroid cancer goes back 70 years, as we’ve been long using it based on the assumption that the majority of high-risk tumors respond to RAI,” he explained.
“But the new paradigm calls for identifying, through molecular analysis, the cancers that have the ability to respond to RAI and/or those that could have the response to RAI enhanced through pretreatment.”
In the statement, published in Thyroid, the working group for the three societies describes their agreement on key issues in three broad areas of RAI use: RAI in perioperative risk stratification, the role of RAI imaging in initial staging, and the need to refine understanding of markers of response to RAI therapy.
Avoid unnecessary treatment
The working group underscores the value of the traditional risk stratification and staging models for thyroid cancer – the American Joint Committee on Cancer eighth edition staging rules and ATA risk stratification system – in the immediate perioperative period, which is well established.
The group supports the inclusion of secondary prognostic factors, specifically molecular markers, in risk stratification in the perioperative period, citing their therapeutic and diagnostic (or theranostic) value in improving individualized treatment decisions.
Molecular theranostics comprise molecular cytology, molecular pathology, and molecular imaging.
“Traditional risk stratification systems can be further refined by ... judicious incorporation of molecular theranostics in the primary framework to guide initial patient management decisions,” the authors wrote.
Dr. Gulec said the inclusion of molecular analysis in risk stratification in particular offers the potential to avoid unnecessary treatment in people who can be identified as likely nonresponders.
“The bottom line is that we need to know more about the cancer before we make decisions on how to tackle it,” he said in an interview.
“For the thyroid cancer to respond to RAI, it has to have an intact system to handle the treatment, and the fact is that most high-risk patients have a molecular profile that does not allow them to respond to RAI or to benefit from total thyroidectomy,” Dr. Gulec explained.
However, the ability to perform a complete genomic analysis with advanced molecular sequencing and identify those patients is radically changing things, he concluded.
Dr. Gulec has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
One in three cancer articles on social media has wrong info
Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.
Among these articles containing misinformation, 76.9% (50/65) contained harmful information.
“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.
“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.
“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”
The study was published online July 22 in the Journal of the National Cancer Institute.
The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.
Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.
One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.
The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.
“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.
Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.
“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.
Dr. Southwell recommends that clinicians be proactive about medical misinformation.
“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.
In short, ask patients what they know about the treatment of their cancer, he suggests.
“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
Study details
For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.
Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.
This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).
Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).
In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).
The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).
A limitation of the study is that it included only the most popular English language cancer articles.
This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.
A version of this article first appeared on Medscape.com.
Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.
Among these articles containing misinformation, 76.9% (50/65) contained harmful information.
“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.
“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.
“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”
The study was published online July 22 in the Journal of the National Cancer Institute.
The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.
Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.
One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.
The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.
“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.
Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.
“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.
Dr. Southwell recommends that clinicians be proactive about medical misinformation.
“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.
In short, ask patients what they know about the treatment of their cancer, he suggests.
“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
Study details
For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.
Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.
This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).
Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).
In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).
The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).
A limitation of the study is that it included only the most popular English language cancer articles.
This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.
A version of this article first appeared on Medscape.com.
Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.
Among these articles containing misinformation, 76.9% (50/65) contained harmful information.
“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.
“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.
“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”
The study was published online July 22 in the Journal of the National Cancer Institute.
The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.
Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.
One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.
The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.
“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.
Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.
“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.
Dr. Southwell recommends that clinicians be proactive about medical misinformation.
“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.
In short, ask patients what they know about the treatment of their cancer, he suggests.
“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
Study details
For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.
Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.
This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).
Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).
In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).
The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).
A limitation of the study is that it included only the most popular English language cancer articles.
This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.
A version of this article first appeared on Medscape.com.
New investigational helmet device shrinks glioblastoma
This is the first time that the wearable Oncomagnetic device was tried with a patient.
The patient had end-stage recurrent glioblastoma and had undergone all standard therapy options. He wore the device for 5 weeks but died from an unrelated injury, so the treatment period was cut short.
A brain scan showed a 31% reduction of contrast-enhanced tumor volume, and an autopsy of his brain confirmed the rapid response to the treatment.
The case study was published online on July 22, 2021, in Frontiers in Oncology.
“I believe that there is a great potential with this device,” said study author David S. Baskin, MD, director of the Kenneth R. Peak Center for Brain and Pituitary Tumor Treatment in the department of neurosurgery at Houston Methodist Hospital. “This is a very exciting time.”
The team is now treating several patients with glioblastoma under compassionate use.
In an independent comment, Adilia Hormigo, MD, PhD, director of the neuro-oncology program at the Tisch Cancer Institute, Mount Sinai Health System, New York, noted that a clinical trial is needed to evaluate the device. “But this is an interesting idea, and we have to be open-minded in treating this fatal disease.”
Oscillating magnetic fields
The Oncomagnetic device consists of three oncoscillators that are attached to the outside of a helmet and are connected to a microprocessor-based electronic controller powered by a rechargeable battery.
It consists of a series of rotating magnets that produce oscillating magnetic fields that cover the entire brain, including the upper part of the brain stem. The device induces rapid apoptosis of glioblastoma cells, Dr. Baskin explained. Its mechanism of action involves disruption of the electron transport in the mitochondrial respiratory chain, causing an elevation of reactive oxygen species and caspase-dependent cancer cell death.
Dr. Baskin emphasized that the new Oncomagnetic device is very different from the Optune device (Novocare), which is already approved by the Food and Drug Administration and has been shown to increase survival among patients with glioblastoma. Optune uses tumor-treating fields (TTFs), which are electromagnetic waves that are delivered via an electric field generator through four transducer arrays that are placed on a shaved scalp. Preclinical studies indicated that the TTFs disrupt cell division by disrupting several steps in the mitotic process that are crucial for cell division.
Both of these devices “are using a type of external maneuver” rather than invasive intracranial approaches, said Dr. Hormingo. The experimental Oncomagnetic device may have an advantage in that it needs to be worn by the patient for fewer hours, she commented. A better understanding of the physics and underlying mechanism is needed, however. Clinical trials are an essential next step.
Most common brain cancer in adults
Glioblastoma is the most common malignant tumor of the brain in adults. Outcomes continue to be dismal. In more than 40 years, median survival has only modestly improved.
“We haven’t gotten very far with glioblastoma despite millions of dollars in research,” Dr. Baskin said. “With treatment, survival is about 15 months, and those are not very good months.”
Out of the box
Standard treatments for glioblastoma include surgery, radiotherapy, and chemotherapy, and many patients cannot tolerate some of these, Dr. Baskin noted. Hence, there is a great need for a different therapeutic approach that yields better outcomes with lower toxicity.
“We didn’t want to develop another chemotherapeutic agent that would help you live another 2 months,” he said in an interview. “We were trying to think out of the box.
“If you want to do something that will really make a difference in an aggressive tumor like glioblastoma, you have to attack something so basic that the tumor can’t evade it,” he said. “For example, with temozolomide, if it is unmethylated, the tumor can repair the DNA damage from the chemotherapy. Even if you’re sensitive to begin with, over time, the tumor will eventually become resistant.”
The new device stems from work by Dr. Baskin and colleagues on mitochondria, which he describes as the powerhouse of the cell. “Mitochondrial DNA can’t repair itself, so if you damage the mitochondria, you will damage the cell, and theoretically, it cannot repair itself,” he said.
In preclinical models, the oscillating magnetic fields generated by the new device were shown to kill patient-derived glioblastoma cells in cell culture without having cytotoxic effects on cortical neurons and normal human astrocytes. Animal studies also showed that it was effective and nontoxic, explained Dr. Baskin.
However, getting the device to human clinical trials has been slow going. “We wanted to start an early-phase trial for an investigational device, but the FDA is overwhelmed with COVID-related applications,” he said. “That has taken priority, and we understand that. So we were able to evaluate it on a patient through compassionate use via the [Food and Drug Administration]–approved Expanded Access Program.”
Exciting possibilities
The patient was a 53-year-old man who had undergone radiotherapy and chemotherapy, and the tumor was progressing. Imaging revealed the presence of leptomeningeal disease, which is associated with a poor outcome and a median survival of 3.5-3.9 months.
The patient was fitted with the helmet device and wore it under supervision for the first 3 days of treatment, during which time the strength of the oscillating magnetic fields was escalated. After this initial supervised phase, the treatment continued at home without supervision, using the same regimen as on the third day.
Treatment was first administered for 2 hours while under supervision and was then gradually increased to a maximum of 6 hours per day. The patient was evaluated clinically on days 7, 16, 30, and 44 after initiation of treatment. No serious adverse events were reported during treatment. The patient’s wife reported subjective improvement in speech and cognitive function.
Dr. Baskin noted that the patient had been experiencing falls for the past year and a half before treatment was initiated. “And then he tripped and fell and sustained a head injury that he subsequently died from,” he said.
Autopsy results confirmed the rapid response to treatment, and tumor shrinkage appeared to correlate with the treatment dose.
“Our results in the laboratory and with this patient open a new world of noninvasive and nontoxic therapy for brain cancer, with many exciting possibilities for the future,” Dr. Baskin commented.
He said his team has experimented with this approach with other tumor types in the laboratory, including triple-negative breast cancer and lung cancer. “We’ve only tried it in a culture so far, but it seems to melt the cancer cells,” he said.
The work was supported by a grant from the Translational Research Initiative of the Houston Methodist Research Institute and several foundations. Dr. Baskin and two coauthors are listed as inventors on a U.S. patent application filed by Houston Methodist Hospital for the device used in this report.
A version of this article first appeared on Medscape.com.
This is the first time that the wearable Oncomagnetic device was tried with a patient.
The patient had end-stage recurrent glioblastoma and had undergone all standard therapy options. He wore the device for 5 weeks but died from an unrelated injury, so the treatment period was cut short.
A brain scan showed a 31% reduction of contrast-enhanced tumor volume, and an autopsy of his brain confirmed the rapid response to the treatment.
The case study was published online on July 22, 2021, in Frontiers in Oncology.
“I believe that there is a great potential with this device,” said study author David S. Baskin, MD, director of the Kenneth R. Peak Center for Brain and Pituitary Tumor Treatment in the department of neurosurgery at Houston Methodist Hospital. “This is a very exciting time.”
The team is now treating several patients with glioblastoma under compassionate use.
In an independent comment, Adilia Hormigo, MD, PhD, director of the neuro-oncology program at the Tisch Cancer Institute, Mount Sinai Health System, New York, noted that a clinical trial is needed to evaluate the device. “But this is an interesting idea, and we have to be open-minded in treating this fatal disease.”
Oscillating magnetic fields
The Oncomagnetic device consists of three oncoscillators that are attached to the outside of a helmet and are connected to a microprocessor-based electronic controller powered by a rechargeable battery.
It consists of a series of rotating magnets that produce oscillating magnetic fields that cover the entire brain, including the upper part of the brain stem. The device induces rapid apoptosis of glioblastoma cells, Dr. Baskin explained. Its mechanism of action involves disruption of the electron transport in the mitochondrial respiratory chain, causing an elevation of reactive oxygen species and caspase-dependent cancer cell death.
Dr. Baskin emphasized that the new Oncomagnetic device is very different from the Optune device (Novocare), which is already approved by the Food and Drug Administration and has been shown to increase survival among patients with glioblastoma. Optune uses tumor-treating fields (TTFs), which are electromagnetic waves that are delivered via an electric field generator through four transducer arrays that are placed on a shaved scalp. Preclinical studies indicated that the TTFs disrupt cell division by disrupting several steps in the mitotic process that are crucial for cell division.
Both of these devices “are using a type of external maneuver” rather than invasive intracranial approaches, said Dr. Hormingo. The experimental Oncomagnetic device may have an advantage in that it needs to be worn by the patient for fewer hours, she commented. A better understanding of the physics and underlying mechanism is needed, however. Clinical trials are an essential next step.
Most common brain cancer in adults
Glioblastoma is the most common malignant tumor of the brain in adults. Outcomes continue to be dismal. In more than 40 years, median survival has only modestly improved.
“We haven’t gotten very far with glioblastoma despite millions of dollars in research,” Dr. Baskin said. “With treatment, survival is about 15 months, and those are not very good months.”
Out of the box
Standard treatments for glioblastoma include surgery, radiotherapy, and chemotherapy, and many patients cannot tolerate some of these, Dr. Baskin noted. Hence, there is a great need for a different therapeutic approach that yields better outcomes with lower toxicity.
“We didn’t want to develop another chemotherapeutic agent that would help you live another 2 months,” he said in an interview. “We were trying to think out of the box.
“If you want to do something that will really make a difference in an aggressive tumor like glioblastoma, you have to attack something so basic that the tumor can’t evade it,” he said. “For example, with temozolomide, if it is unmethylated, the tumor can repair the DNA damage from the chemotherapy. Even if you’re sensitive to begin with, over time, the tumor will eventually become resistant.”
The new device stems from work by Dr. Baskin and colleagues on mitochondria, which he describes as the powerhouse of the cell. “Mitochondrial DNA can’t repair itself, so if you damage the mitochondria, you will damage the cell, and theoretically, it cannot repair itself,” he said.
In preclinical models, the oscillating magnetic fields generated by the new device were shown to kill patient-derived glioblastoma cells in cell culture without having cytotoxic effects on cortical neurons and normal human astrocytes. Animal studies also showed that it was effective and nontoxic, explained Dr. Baskin.
However, getting the device to human clinical trials has been slow going. “We wanted to start an early-phase trial for an investigational device, but the FDA is overwhelmed with COVID-related applications,” he said. “That has taken priority, and we understand that. So we were able to evaluate it on a patient through compassionate use via the [Food and Drug Administration]–approved Expanded Access Program.”
Exciting possibilities
The patient was a 53-year-old man who had undergone radiotherapy and chemotherapy, and the tumor was progressing. Imaging revealed the presence of leptomeningeal disease, which is associated with a poor outcome and a median survival of 3.5-3.9 months.
The patient was fitted with the helmet device and wore it under supervision for the first 3 days of treatment, during which time the strength of the oscillating magnetic fields was escalated. After this initial supervised phase, the treatment continued at home without supervision, using the same regimen as on the third day.
Treatment was first administered for 2 hours while under supervision and was then gradually increased to a maximum of 6 hours per day. The patient was evaluated clinically on days 7, 16, 30, and 44 after initiation of treatment. No serious adverse events were reported during treatment. The patient’s wife reported subjective improvement in speech and cognitive function.
Dr. Baskin noted that the patient had been experiencing falls for the past year and a half before treatment was initiated. “And then he tripped and fell and sustained a head injury that he subsequently died from,” he said.
Autopsy results confirmed the rapid response to treatment, and tumor shrinkage appeared to correlate with the treatment dose.
“Our results in the laboratory and with this patient open a new world of noninvasive and nontoxic therapy for brain cancer, with many exciting possibilities for the future,” Dr. Baskin commented.
He said his team has experimented with this approach with other tumor types in the laboratory, including triple-negative breast cancer and lung cancer. “We’ve only tried it in a culture so far, but it seems to melt the cancer cells,” he said.
The work was supported by a grant from the Translational Research Initiative of the Houston Methodist Research Institute and several foundations. Dr. Baskin and two coauthors are listed as inventors on a U.S. patent application filed by Houston Methodist Hospital for the device used in this report.
A version of this article first appeared on Medscape.com.
This is the first time that the wearable Oncomagnetic device was tried with a patient.
The patient had end-stage recurrent glioblastoma and had undergone all standard therapy options. He wore the device for 5 weeks but died from an unrelated injury, so the treatment period was cut short.
A brain scan showed a 31% reduction of contrast-enhanced tumor volume, and an autopsy of his brain confirmed the rapid response to the treatment.
The case study was published online on July 22, 2021, in Frontiers in Oncology.
“I believe that there is a great potential with this device,” said study author David S. Baskin, MD, director of the Kenneth R. Peak Center for Brain and Pituitary Tumor Treatment in the department of neurosurgery at Houston Methodist Hospital. “This is a very exciting time.”
The team is now treating several patients with glioblastoma under compassionate use.
In an independent comment, Adilia Hormigo, MD, PhD, director of the neuro-oncology program at the Tisch Cancer Institute, Mount Sinai Health System, New York, noted that a clinical trial is needed to evaluate the device. “But this is an interesting idea, and we have to be open-minded in treating this fatal disease.”
Oscillating magnetic fields
The Oncomagnetic device consists of three oncoscillators that are attached to the outside of a helmet and are connected to a microprocessor-based electronic controller powered by a rechargeable battery.
It consists of a series of rotating magnets that produce oscillating magnetic fields that cover the entire brain, including the upper part of the brain stem. The device induces rapid apoptosis of glioblastoma cells, Dr. Baskin explained. Its mechanism of action involves disruption of the electron transport in the mitochondrial respiratory chain, causing an elevation of reactive oxygen species and caspase-dependent cancer cell death.
Dr. Baskin emphasized that the new Oncomagnetic device is very different from the Optune device (Novocare), which is already approved by the Food and Drug Administration and has been shown to increase survival among patients with glioblastoma. Optune uses tumor-treating fields (TTFs), which are electromagnetic waves that are delivered via an electric field generator through four transducer arrays that are placed on a shaved scalp. Preclinical studies indicated that the TTFs disrupt cell division by disrupting several steps in the mitotic process that are crucial for cell division.
Both of these devices “are using a type of external maneuver” rather than invasive intracranial approaches, said Dr. Hormingo. The experimental Oncomagnetic device may have an advantage in that it needs to be worn by the patient for fewer hours, she commented. A better understanding of the physics and underlying mechanism is needed, however. Clinical trials are an essential next step.
Most common brain cancer in adults
Glioblastoma is the most common malignant tumor of the brain in adults. Outcomes continue to be dismal. In more than 40 years, median survival has only modestly improved.
“We haven’t gotten very far with glioblastoma despite millions of dollars in research,” Dr. Baskin said. “With treatment, survival is about 15 months, and those are not very good months.”
Out of the box
Standard treatments for glioblastoma include surgery, radiotherapy, and chemotherapy, and many patients cannot tolerate some of these, Dr. Baskin noted. Hence, there is a great need for a different therapeutic approach that yields better outcomes with lower toxicity.
“We didn’t want to develop another chemotherapeutic agent that would help you live another 2 months,” he said in an interview. “We were trying to think out of the box.
“If you want to do something that will really make a difference in an aggressive tumor like glioblastoma, you have to attack something so basic that the tumor can’t evade it,” he said. “For example, with temozolomide, if it is unmethylated, the tumor can repair the DNA damage from the chemotherapy. Even if you’re sensitive to begin with, over time, the tumor will eventually become resistant.”
The new device stems from work by Dr. Baskin and colleagues on mitochondria, which he describes as the powerhouse of the cell. “Mitochondrial DNA can’t repair itself, so if you damage the mitochondria, you will damage the cell, and theoretically, it cannot repair itself,” he said.
In preclinical models, the oscillating magnetic fields generated by the new device were shown to kill patient-derived glioblastoma cells in cell culture without having cytotoxic effects on cortical neurons and normal human astrocytes. Animal studies also showed that it was effective and nontoxic, explained Dr. Baskin.
However, getting the device to human clinical trials has been slow going. “We wanted to start an early-phase trial for an investigational device, but the FDA is overwhelmed with COVID-related applications,” he said. “That has taken priority, and we understand that. So we were able to evaluate it on a patient through compassionate use via the [Food and Drug Administration]–approved Expanded Access Program.”
Exciting possibilities
The patient was a 53-year-old man who had undergone radiotherapy and chemotherapy, and the tumor was progressing. Imaging revealed the presence of leptomeningeal disease, which is associated with a poor outcome and a median survival of 3.5-3.9 months.
The patient was fitted with the helmet device and wore it under supervision for the first 3 days of treatment, during which time the strength of the oscillating magnetic fields was escalated. After this initial supervised phase, the treatment continued at home without supervision, using the same regimen as on the third day.
Treatment was first administered for 2 hours while under supervision and was then gradually increased to a maximum of 6 hours per day. The patient was evaluated clinically on days 7, 16, 30, and 44 after initiation of treatment. No serious adverse events were reported during treatment. The patient’s wife reported subjective improvement in speech and cognitive function.
Dr. Baskin noted that the patient had been experiencing falls for the past year and a half before treatment was initiated. “And then he tripped and fell and sustained a head injury that he subsequently died from,” he said.
Autopsy results confirmed the rapid response to treatment, and tumor shrinkage appeared to correlate with the treatment dose.
“Our results in the laboratory and with this patient open a new world of noninvasive and nontoxic therapy for brain cancer, with many exciting possibilities for the future,” Dr. Baskin commented.
He said his team has experimented with this approach with other tumor types in the laboratory, including triple-negative breast cancer and lung cancer. “We’ve only tried it in a culture so far, but it seems to melt the cancer cells,” he said.
The work was supported by a grant from the Translational Research Initiative of the Houston Methodist Research Institute and several foundations. Dr. Baskin and two coauthors are listed as inventors on a U.S. patent application filed by Houston Methodist Hospital for the device used in this report.
A version of this article first appeared on Medscape.com.
More children with high-risk brain cancer now surviving
A practice-changing study that used molecular testing to distinguish between subtypes of medulloblastoma has shown a significant improvement in survival for children with high-risk disease who underwent treatment intensification with carboplatin.
“Each of the four subgroups of medulloblastoma has a different prognosis, but for this particular subgroup, 20 fewer children out of every 100 would have survived prior to this study,” James Olson, MD, professor of medicine, French Hutchinson Cancer Research Center, University of Washington, Seattle, said in an interview.
“This is the reason for celebration – for now and forevermore, we can expect 20 more children with high-risk, group 3 medulloblastoma to survive,” he said.
“We recommend that all children with high-risk, group 3 medulloblastoma receive carboplatin and all children in the other subgroups do not, because we don’t want them to experience the toxicity without benefit,” Dr. Olson said.
The study was published online July 22, 2021, in JAMA Oncology.
Hematologic toxicity was more pronounced in the carboplatin arm in the induction phase of the protocol, and toxicity persisted into the first cycles of maintenance therapy. On the other hand, “there weren’t enough additional side effects to recommend children not get carboplatin if they would benefit from it,” Dr. Olson noted.
At least 75% of children with newly diagnosed medulloblastoma survive, although those with high-risk, group 3 disease have a substantially poorer prognosis than those with other molecular subtypes.
However, if a child with medulloblastoma experiences relapse, “the likelihood of survival is near zero, so it’s important to get it right the first time,” Dr. Olson said.
One of the patients who took part in this trial, Sammy Loch of Seattle, is now 27 years old and has been cancer free for 11 years.
She was diagnosed with medulloblastoma when in high school. At the time of her diagnosis, she was asked by her pediatric oncologist at Seattle Children’s Hospital about taking part in the study. After careful consideration, she agreed.
“Participating in research was my way to give back and pay it forward,” Ms. Loch said in a statement. “It’s really exciting to know more people will survive because of the research I was involved in,” she added. She continues to pay her debt forward, serving as a therapist for people with chronic health conditions and raising funds for pediatric cancer research.
Patients had high-risk features
The study involved 261 evaluable patients (median age, 8.6 years). All patients had high-risk features, including metastatic disease (72.4% of the group), diffuse anaplastic histologic characteristics (22.2%), and incomplete surgical resection (5.4%), defined as residual tumor greater than 1.5 cm2.
“All patients received 36 Gy craniospinal radiotherapy with boost to the posterior fossa of 55.8 Gy cumulative dose with conventional fractionation of 1.8 Gy/d,” Dr. Olson and colleagues explain. Patients also received six doses of vincristine 1.5 mg/m2 weekly during radiotherapy and were randomly assigned to receive carboplatin 35 mg/m2 for a total of 30 doses given daily prior to radiotherapy or placebo.
This regimen was followed by maintenance therapy, which consisted of six 28-day cycles of the combination of cisplatin 75 mg/m2 on day 1; cyclophosphamide 1,000 mg/m2 on days 2 and 3; and vincristine 1.5 mg/m2 on days 1 and 8.
Patients were originally assigned to receive an additional 12 cycles of isotretinoin or placebo, to be given during and after maintenance therapy. However, randomization to isotretinoin was discontinued early because of futility.
The study was initially powered to evaluate medulloblastoma as a single disease. However, as a result of biologic insights gained after the study was conceived, it was amended to include a molecular subgroup analysis to better distinguish patients who might truly benefit from intensified therapy, the authors explained.
Study results
The World Health Organization categorizes tumors of the central nervous system into four groups. The authors followed this system of categorization for their patients with medulloblastoma. The four groups are WNT, in which WNT signaling pathway is activated; SHH, in which the SHH signaling pathway is activated; with or without TP53 mutation (provisionally designated group 3); and non-WNT/non-SHH (provisionally designed group 4)
The primary endpoint of the trial was event-free survival (EFS). In the patient population overall, there was no significant difference regarding this endpoint among those who received carboplatin and those who did not (EFS at 5 years, 66.4% vs. 59.2%).
However, there was a significant improvement among the patients in subgroup 3. Among those patients, EFS at 5 years was 73.2% with carboplatin versus 53.7% without (P = .047).
Similarly, in the overall group, there was no significant improvement in overall survival (OS) at 5 years from the addition of carboplatin (77.6% vs. 68.8% without carboplatin). However, the OS at 5 years varied widely between the different subtypes. There was again a significant improvement in OS at 5 years among the patients in subgroup 3 (82% with carboplation vs 63.7% without).
The beneficial effects from the addition of carboplatin on both endpoints were seen exclusively in patients in group 3, the authors emphasized.
“The WNT group does really well with less therapy, so if we treated all children the same, we would likely be overtreating WNT children and undertreating group 3 children,” Dr. Olson observed. “Genetic analysis is essential.”
In an earlier study, Dr. Olson and colleagues found that 70% of children with primitive neuroectodermal tumor of the CNS and pineoblastoma had been misdiagnosed even by outstanding children’s oncology centers because clinicians were relying on microscopic diagnosis.
“With molecular diagnosis, we were able to learn that many of these children had completely different diseases that require complexly different treatments, so doing diagnosis by molecular classification is absolutely essential,” he reemphasized.
“Glimmers of hope”
This study provides clinicians with “glimmers of hope” that children with high-risk, group 3 medulloblastoma will experience improvements in survival, wrote Allison Martin, MD, Albert Einstein College of Medicine, New York, and Sadhana Jackson, MD, National Institutes of Health, Bethesda, M.d., in an accompanying editorial.
The editorialists hope that “the treatment paradigm for all patients with high-risk disease can be improved through incorporation of detailed molecular analyses.”
However, they pointed out that DNA methylation and other advanced testing methods used to distinguish subgroups 3 and 4 in this study are not widely available, even at most Children’s Oncology Group member institutions. (Dr. Olson countered that, even if these sophisticated tests are not available at all pediatric oncology centers, tests will be performed if clinicians send tissue to the few sites that are equipped to conduct them.)
The editorialists also noted that therapy intensification with carboplatin is associated with an increased risk for adverse effects – “underscoring the importance of correctly identifying patients who could benefit from this intervention and avoid unnecessary toxic effects.”
The study was funded by the National Cancer Institute. Dr. Olson has disclosed no relevant financial relationships. Dr. Martin reported that she previously owed shares in Celgene, which she has subsequently sold.
A version of this article first appeared on Medscape.com.
A practice-changing study that used molecular testing to distinguish between subtypes of medulloblastoma has shown a significant improvement in survival for children with high-risk disease who underwent treatment intensification with carboplatin.
“Each of the four subgroups of medulloblastoma has a different prognosis, but for this particular subgroup, 20 fewer children out of every 100 would have survived prior to this study,” James Olson, MD, professor of medicine, French Hutchinson Cancer Research Center, University of Washington, Seattle, said in an interview.
“This is the reason for celebration – for now and forevermore, we can expect 20 more children with high-risk, group 3 medulloblastoma to survive,” he said.
“We recommend that all children with high-risk, group 3 medulloblastoma receive carboplatin and all children in the other subgroups do not, because we don’t want them to experience the toxicity without benefit,” Dr. Olson said.
The study was published online July 22, 2021, in JAMA Oncology.
Hematologic toxicity was more pronounced in the carboplatin arm in the induction phase of the protocol, and toxicity persisted into the first cycles of maintenance therapy. On the other hand, “there weren’t enough additional side effects to recommend children not get carboplatin if they would benefit from it,” Dr. Olson noted.
At least 75% of children with newly diagnosed medulloblastoma survive, although those with high-risk, group 3 disease have a substantially poorer prognosis than those with other molecular subtypes.
However, if a child with medulloblastoma experiences relapse, “the likelihood of survival is near zero, so it’s important to get it right the first time,” Dr. Olson said.
One of the patients who took part in this trial, Sammy Loch of Seattle, is now 27 years old and has been cancer free for 11 years.
She was diagnosed with medulloblastoma when in high school. At the time of her diagnosis, she was asked by her pediatric oncologist at Seattle Children’s Hospital about taking part in the study. After careful consideration, she agreed.
“Participating in research was my way to give back and pay it forward,” Ms. Loch said in a statement. “It’s really exciting to know more people will survive because of the research I was involved in,” she added. She continues to pay her debt forward, serving as a therapist for people with chronic health conditions and raising funds for pediatric cancer research.
Patients had high-risk features
The study involved 261 evaluable patients (median age, 8.6 years). All patients had high-risk features, including metastatic disease (72.4% of the group), diffuse anaplastic histologic characteristics (22.2%), and incomplete surgical resection (5.4%), defined as residual tumor greater than 1.5 cm2.
“All patients received 36 Gy craniospinal radiotherapy with boost to the posterior fossa of 55.8 Gy cumulative dose with conventional fractionation of 1.8 Gy/d,” Dr. Olson and colleagues explain. Patients also received six doses of vincristine 1.5 mg/m2 weekly during radiotherapy and were randomly assigned to receive carboplatin 35 mg/m2 for a total of 30 doses given daily prior to radiotherapy or placebo.
This regimen was followed by maintenance therapy, which consisted of six 28-day cycles of the combination of cisplatin 75 mg/m2 on day 1; cyclophosphamide 1,000 mg/m2 on days 2 and 3; and vincristine 1.5 mg/m2 on days 1 and 8.
Patients were originally assigned to receive an additional 12 cycles of isotretinoin or placebo, to be given during and after maintenance therapy. However, randomization to isotretinoin was discontinued early because of futility.
The study was initially powered to evaluate medulloblastoma as a single disease. However, as a result of biologic insights gained after the study was conceived, it was amended to include a molecular subgroup analysis to better distinguish patients who might truly benefit from intensified therapy, the authors explained.
Study results
The World Health Organization categorizes tumors of the central nervous system into four groups. The authors followed this system of categorization for their patients with medulloblastoma. The four groups are WNT, in which WNT signaling pathway is activated; SHH, in which the SHH signaling pathway is activated; with or without TP53 mutation (provisionally designated group 3); and non-WNT/non-SHH (provisionally designed group 4)
The primary endpoint of the trial was event-free survival (EFS). In the patient population overall, there was no significant difference regarding this endpoint among those who received carboplatin and those who did not (EFS at 5 years, 66.4% vs. 59.2%).
However, there was a significant improvement among the patients in subgroup 3. Among those patients, EFS at 5 years was 73.2% with carboplatin versus 53.7% without (P = .047).
Similarly, in the overall group, there was no significant improvement in overall survival (OS) at 5 years from the addition of carboplatin (77.6% vs. 68.8% without carboplatin). However, the OS at 5 years varied widely between the different subtypes. There was again a significant improvement in OS at 5 years among the patients in subgroup 3 (82% with carboplation vs 63.7% without).
The beneficial effects from the addition of carboplatin on both endpoints were seen exclusively in patients in group 3, the authors emphasized.
“The WNT group does really well with less therapy, so if we treated all children the same, we would likely be overtreating WNT children and undertreating group 3 children,” Dr. Olson observed. “Genetic analysis is essential.”
In an earlier study, Dr. Olson and colleagues found that 70% of children with primitive neuroectodermal tumor of the CNS and pineoblastoma had been misdiagnosed even by outstanding children’s oncology centers because clinicians were relying on microscopic diagnosis.
“With molecular diagnosis, we were able to learn that many of these children had completely different diseases that require complexly different treatments, so doing diagnosis by molecular classification is absolutely essential,” he reemphasized.
“Glimmers of hope”
This study provides clinicians with “glimmers of hope” that children with high-risk, group 3 medulloblastoma will experience improvements in survival, wrote Allison Martin, MD, Albert Einstein College of Medicine, New York, and Sadhana Jackson, MD, National Institutes of Health, Bethesda, M.d., in an accompanying editorial.
The editorialists hope that “the treatment paradigm for all patients with high-risk disease can be improved through incorporation of detailed molecular analyses.”
However, they pointed out that DNA methylation and other advanced testing methods used to distinguish subgroups 3 and 4 in this study are not widely available, even at most Children’s Oncology Group member institutions. (Dr. Olson countered that, even if these sophisticated tests are not available at all pediatric oncology centers, tests will be performed if clinicians send tissue to the few sites that are equipped to conduct them.)
The editorialists also noted that therapy intensification with carboplatin is associated with an increased risk for adverse effects – “underscoring the importance of correctly identifying patients who could benefit from this intervention and avoid unnecessary toxic effects.”
The study was funded by the National Cancer Institute. Dr. Olson has disclosed no relevant financial relationships. Dr. Martin reported that she previously owed shares in Celgene, which she has subsequently sold.
A version of this article first appeared on Medscape.com.
A practice-changing study that used molecular testing to distinguish between subtypes of medulloblastoma has shown a significant improvement in survival for children with high-risk disease who underwent treatment intensification with carboplatin.
“Each of the four subgroups of medulloblastoma has a different prognosis, but for this particular subgroup, 20 fewer children out of every 100 would have survived prior to this study,” James Olson, MD, professor of medicine, French Hutchinson Cancer Research Center, University of Washington, Seattle, said in an interview.
“This is the reason for celebration – for now and forevermore, we can expect 20 more children with high-risk, group 3 medulloblastoma to survive,” he said.
“We recommend that all children with high-risk, group 3 medulloblastoma receive carboplatin and all children in the other subgroups do not, because we don’t want them to experience the toxicity without benefit,” Dr. Olson said.
The study was published online July 22, 2021, in JAMA Oncology.
Hematologic toxicity was more pronounced in the carboplatin arm in the induction phase of the protocol, and toxicity persisted into the first cycles of maintenance therapy. On the other hand, “there weren’t enough additional side effects to recommend children not get carboplatin if they would benefit from it,” Dr. Olson noted.
At least 75% of children with newly diagnosed medulloblastoma survive, although those with high-risk, group 3 disease have a substantially poorer prognosis than those with other molecular subtypes.
However, if a child with medulloblastoma experiences relapse, “the likelihood of survival is near zero, so it’s important to get it right the first time,” Dr. Olson said.
One of the patients who took part in this trial, Sammy Loch of Seattle, is now 27 years old and has been cancer free for 11 years.
She was diagnosed with medulloblastoma when in high school. At the time of her diagnosis, she was asked by her pediatric oncologist at Seattle Children’s Hospital about taking part in the study. After careful consideration, she agreed.
“Participating in research was my way to give back and pay it forward,” Ms. Loch said in a statement. “It’s really exciting to know more people will survive because of the research I was involved in,” she added. She continues to pay her debt forward, serving as a therapist for people with chronic health conditions and raising funds for pediatric cancer research.
Patients had high-risk features
The study involved 261 evaluable patients (median age, 8.6 years). All patients had high-risk features, including metastatic disease (72.4% of the group), diffuse anaplastic histologic characteristics (22.2%), and incomplete surgical resection (5.4%), defined as residual tumor greater than 1.5 cm2.
“All patients received 36 Gy craniospinal radiotherapy with boost to the posterior fossa of 55.8 Gy cumulative dose with conventional fractionation of 1.8 Gy/d,” Dr. Olson and colleagues explain. Patients also received six doses of vincristine 1.5 mg/m2 weekly during radiotherapy and were randomly assigned to receive carboplatin 35 mg/m2 for a total of 30 doses given daily prior to radiotherapy or placebo.
This regimen was followed by maintenance therapy, which consisted of six 28-day cycles of the combination of cisplatin 75 mg/m2 on day 1; cyclophosphamide 1,000 mg/m2 on days 2 and 3; and vincristine 1.5 mg/m2 on days 1 and 8.
Patients were originally assigned to receive an additional 12 cycles of isotretinoin or placebo, to be given during and after maintenance therapy. However, randomization to isotretinoin was discontinued early because of futility.
The study was initially powered to evaluate medulloblastoma as a single disease. However, as a result of biologic insights gained after the study was conceived, it was amended to include a molecular subgroup analysis to better distinguish patients who might truly benefit from intensified therapy, the authors explained.
Study results
The World Health Organization categorizes tumors of the central nervous system into four groups. The authors followed this system of categorization for their patients with medulloblastoma. The four groups are WNT, in which WNT signaling pathway is activated; SHH, in which the SHH signaling pathway is activated; with or without TP53 mutation (provisionally designated group 3); and non-WNT/non-SHH (provisionally designed group 4)
The primary endpoint of the trial was event-free survival (EFS). In the patient population overall, there was no significant difference regarding this endpoint among those who received carboplatin and those who did not (EFS at 5 years, 66.4% vs. 59.2%).
However, there was a significant improvement among the patients in subgroup 3. Among those patients, EFS at 5 years was 73.2% with carboplatin versus 53.7% without (P = .047).
Similarly, in the overall group, there was no significant improvement in overall survival (OS) at 5 years from the addition of carboplatin (77.6% vs. 68.8% without carboplatin). However, the OS at 5 years varied widely between the different subtypes. There was again a significant improvement in OS at 5 years among the patients in subgroup 3 (82% with carboplation vs 63.7% without).
The beneficial effects from the addition of carboplatin on both endpoints were seen exclusively in patients in group 3, the authors emphasized.
“The WNT group does really well with less therapy, so if we treated all children the same, we would likely be overtreating WNT children and undertreating group 3 children,” Dr. Olson observed. “Genetic analysis is essential.”
In an earlier study, Dr. Olson and colleagues found that 70% of children with primitive neuroectodermal tumor of the CNS and pineoblastoma had been misdiagnosed even by outstanding children’s oncology centers because clinicians were relying on microscopic diagnosis.
“With molecular diagnosis, we were able to learn that many of these children had completely different diseases that require complexly different treatments, so doing diagnosis by molecular classification is absolutely essential,” he reemphasized.
“Glimmers of hope”
This study provides clinicians with “glimmers of hope” that children with high-risk, group 3 medulloblastoma will experience improvements in survival, wrote Allison Martin, MD, Albert Einstein College of Medicine, New York, and Sadhana Jackson, MD, National Institutes of Health, Bethesda, M.d., in an accompanying editorial.
The editorialists hope that “the treatment paradigm for all patients with high-risk disease can be improved through incorporation of detailed molecular analyses.”
However, they pointed out that DNA methylation and other advanced testing methods used to distinguish subgroups 3 and 4 in this study are not widely available, even at most Children’s Oncology Group member institutions. (Dr. Olson countered that, even if these sophisticated tests are not available at all pediatric oncology centers, tests will be performed if clinicians send tissue to the few sites that are equipped to conduct them.)
The editorialists also noted that therapy intensification with carboplatin is associated with an increased risk for adverse effects – “underscoring the importance of correctly identifying patients who could benefit from this intervention and avoid unnecessary toxic effects.”
The study was funded by the National Cancer Institute. Dr. Olson has disclosed no relevant financial relationships. Dr. Martin reported that she previously owed shares in Celgene, which she has subsequently sold.
A version of this article first appeared on Medscape.com.
Adjuvant capecitabine shown a less punishing option after NPC chemoradiation
Adjuvant capecitabine is an effective and better tolerated alternative to chemotherapy following chemoradiation for locoregionally advanced nasopharyngeal carcinoma, according to two phase 3 trials from China.
Despite using different dosing strategies, 3-year failure-free survival approached 90% in both trials, comparable to the standard approach with adjuvant platinum doublets, but with better compliance.
The study teams were looking for “a way to make adjuvant therapy more tolerable,” said oncologist Herbert Loong, MBBS, clinical associate professor at the Chinese University of Hong Kong, who discussed both trials after they were presented at the American Society for Clinical Oncology annual meeting.
Compliance is low with platinum doublets because of the toxicity. About 60%-70% of patients can tolerate 2-3 cycles after chemoradiation, and about a third can’t even start because of the toll chemoradiation took on their bodies, he said.
Induction chemotherapy is an alternative, but patients seem to derive more benefit form adjuvant therapy after chemoradiation. Indeed, “given the fact that we may now have a well established, well tolerated adjuvant therapy for our patients” – capecitabine – “the role of induction therapy” is in question, Dr. Loong said.
Metronomic dosing
One trial randomized 204 patients to metronomic dosing of capecitabine, 650 mg/m2 twice daily for 1 year within 12 to 16 weeks after the last radiation, and 202 others to observation.
The idea of metronomic dosing was to give a lower dose of the agent over a longer period to reduce side effects and perhaps improve efficacy.
Subjects had high-risk stage III to IVA disease with no locoregional disease or distant metastasis after chemoradiotherapy. Almost 80% in both arms also had induction chemotherapy, most commonly docetaxel and cisplatin.
Almost three-quarters of people in the treatment arm complied with capecitabine for an entire year.
At a median follow-up of 38 months, 3-year failure-free survival was 85.3% with metronomic capecitabine vs. 75.7% with observation (hazard ratio, .50, P = .002). Three-year overall survival was 93.3% with capecitabine and 88.6% with observation (HR .44, P = .018).
The incidence of grade 3/4 adverse events was 17.4% with metronomic capecitabine vs. 5.5% with observation. Hand-foot syndrome was the most common complication, occurring in 9% of capecitabine subjects. There were no treatment-related deaths, and there was no clinically meaningful deterioration in quality of life associated with treatment.
The approach “significantly improved” outcomes, “with a manageable safety profile and no compromise to quality of life ... Metronomic adjuvant capecitabine can be an option for first-line treatment in this high-risk” group, concluded investigators led by Jun Ma, MD, professor of radiation oncology and deputy president of Sun Yat-sen University Cancer Center in Guangzhou, China.
Standard dosing
The second trial used standard dosing. The researchers randomized 90 subjects to capecitabine 1,000 mg/m2 twice daily for 14 days in eight 21-day cycles after chemoradiation; 90 subjects were randomized to observation. None of the subjects received induction chemotherapy.
Patients had stage III-IVb disease plus at least one high-risk feature, such as high Epstein Barr virus DNA titers. The majority of patients in both arms had three or more high risk features.
Over 80% of capecitabine subjects completed all eight cycles of treatment.
At a median follow-up of 44.8 months, 3-year failure-free survival was 87.7% with capecitabine vs. 73.3% in the control arm (HR .52, P = .037). Three-year overall survival was 92.6% with capecitabine vs. 88.9% with observation, which wasn’t statistically significant.
The incidence of acute grade 3/4 adverse events was 57.8% with standard dose capecitabine. Rates of hand foot syndrome, mucositis, anemia, and other problems were substantially higher than with observation.
For high-risk patients unable to tolerate chemotherapy, adjuvant capecitabine is a “suitable alternative treatment option,” said lead investigator Jingjing Miao, MD, of the department of nasopharyngeal carcinoma at Sun Yat-sen University Cancer Center, Guangzhou, China.
The trials were funded by Sun Yat-sen University and others. The investigators had no disclosures. Dr. Loong is an adviser, speaker, and/or researcher for a number of companies, including Novartis, Pfizer, and Lilly.
Adjuvant capecitabine is an effective and better tolerated alternative to chemotherapy following chemoradiation for locoregionally advanced nasopharyngeal carcinoma, according to two phase 3 trials from China.
Despite using different dosing strategies, 3-year failure-free survival approached 90% in both trials, comparable to the standard approach with adjuvant platinum doublets, but with better compliance.
The study teams were looking for “a way to make adjuvant therapy more tolerable,” said oncologist Herbert Loong, MBBS, clinical associate professor at the Chinese University of Hong Kong, who discussed both trials after they were presented at the American Society for Clinical Oncology annual meeting.
Compliance is low with platinum doublets because of the toxicity. About 60%-70% of patients can tolerate 2-3 cycles after chemoradiation, and about a third can’t even start because of the toll chemoradiation took on their bodies, he said.
Induction chemotherapy is an alternative, but patients seem to derive more benefit form adjuvant therapy after chemoradiation. Indeed, “given the fact that we may now have a well established, well tolerated adjuvant therapy for our patients” – capecitabine – “the role of induction therapy” is in question, Dr. Loong said.
Metronomic dosing
One trial randomized 204 patients to metronomic dosing of capecitabine, 650 mg/m2 twice daily for 1 year within 12 to 16 weeks after the last radiation, and 202 others to observation.
The idea of metronomic dosing was to give a lower dose of the agent over a longer period to reduce side effects and perhaps improve efficacy.
Subjects had high-risk stage III to IVA disease with no locoregional disease or distant metastasis after chemoradiotherapy. Almost 80% in both arms also had induction chemotherapy, most commonly docetaxel and cisplatin.
Almost three-quarters of people in the treatment arm complied with capecitabine for an entire year.
At a median follow-up of 38 months, 3-year failure-free survival was 85.3% with metronomic capecitabine vs. 75.7% with observation (hazard ratio, .50, P = .002). Three-year overall survival was 93.3% with capecitabine and 88.6% with observation (HR .44, P = .018).
The incidence of grade 3/4 adverse events was 17.4% with metronomic capecitabine vs. 5.5% with observation. Hand-foot syndrome was the most common complication, occurring in 9% of capecitabine subjects. There were no treatment-related deaths, and there was no clinically meaningful deterioration in quality of life associated with treatment.
The approach “significantly improved” outcomes, “with a manageable safety profile and no compromise to quality of life ... Metronomic adjuvant capecitabine can be an option for first-line treatment in this high-risk” group, concluded investigators led by Jun Ma, MD, professor of radiation oncology and deputy president of Sun Yat-sen University Cancer Center in Guangzhou, China.
Standard dosing
The second trial used standard dosing. The researchers randomized 90 subjects to capecitabine 1,000 mg/m2 twice daily for 14 days in eight 21-day cycles after chemoradiation; 90 subjects were randomized to observation. None of the subjects received induction chemotherapy.
Patients had stage III-IVb disease plus at least one high-risk feature, such as high Epstein Barr virus DNA titers. The majority of patients in both arms had three or more high risk features.
Over 80% of capecitabine subjects completed all eight cycles of treatment.
At a median follow-up of 44.8 months, 3-year failure-free survival was 87.7% with capecitabine vs. 73.3% in the control arm (HR .52, P = .037). Three-year overall survival was 92.6% with capecitabine vs. 88.9% with observation, which wasn’t statistically significant.
The incidence of acute grade 3/4 adverse events was 57.8% with standard dose capecitabine. Rates of hand foot syndrome, mucositis, anemia, and other problems were substantially higher than with observation.
For high-risk patients unable to tolerate chemotherapy, adjuvant capecitabine is a “suitable alternative treatment option,” said lead investigator Jingjing Miao, MD, of the department of nasopharyngeal carcinoma at Sun Yat-sen University Cancer Center, Guangzhou, China.
The trials were funded by Sun Yat-sen University and others. The investigators had no disclosures. Dr. Loong is an adviser, speaker, and/or researcher for a number of companies, including Novartis, Pfizer, and Lilly.
Adjuvant capecitabine is an effective and better tolerated alternative to chemotherapy following chemoradiation for locoregionally advanced nasopharyngeal carcinoma, according to two phase 3 trials from China.
Despite using different dosing strategies, 3-year failure-free survival approached 90% in both trials, comparable to the standard approach with adjuvant platinum doublets, but with better compliance.
The study teams were looking for “a way to make adjuvant therapy more tolerable,” said oncologist Herbert Loong, MBBS, clinical associate professor at the Chinese University of Hong Kong, who discussed both trials after they were presented at the American Society for Clinical Oncology annual meeting.
Compliance is low with platinum doublets because of the toxicity. About 60%-70% of patients can tolerate 2-3 cycles after chemoradiation, and about a third can’t even start because of the toll chemoradiation took on their bodies, he said.
Induction chemotherapy is an alternative, but patients seem to derive more benefit form adjuvant therapy after chemoradiation. Indeed, “given the fact that we may now have a well established, well tolerated adjuvant therapy for our patients” – capecitabine – “the role of induction therapy” is in question, Dr. Loong said.
Metronomic dosing
One trial randomized 204 patients to metronomic dosing of capecitabine, 650 mg/m2 twice daily for 1 year within 12 to 16 weeks after the last radiation, and 202 others to observation.
The idea of metronomic dosing was to give a lower dose of the agent over a longer period to reduce side effects and perhaps improve efficacy.
Subjects had high-risk stage III to IVA disease with no locoregional disease or distant metastasis after chemoradiotherapy. Almost 80% in both arms also had induction chemotherapy, most commonly docetaxel and cisplatin.
Almost three-quarters of people in the treatment arm complied with capecitabine for an entire year.
At a median follow-up of 38 months, 3-year failure-free survival was 85.3% with metronomic capecitabine vs. 75.7% with observation (hazard ratio, .50, P = .002). Three-year overall survival was 93.3% with capecitabine and 88.6% with observation (HR .44, P = .018).
The incidence of grade 3/4 adverse events was 17.4% with metronomic capecitabine vs. 5.5% with observation. Hand-foot syndrome was the most common complication, occurring in 9% of capecitabine subjects. There were no treatment-related deaths, and there was no clinically meaningful deterioration in quality of life associated with treatment.
The approach “significantly improved” outcomes, “with a manageable safety profile and no compromise to quality of life ... Metronomic adjuvant capecitabine can be an option for first-line treatment in this high-risk” group, concluded investigators led by Jun Ma, MD, professor of radiation oncology and deputy president of Sun Yat-sen University Cancer Center in Guangzhou, China.
Standard dosing
The second trial used standard dosing. The researchers randomized 90 subjects to capecitabine 1,000 mg/m2 twice daily for 14 days in eight 21-day cycles after chemoradiation; 90 subjects were randomized to observation. None of the subjects received induction chemotherapy.
Patients had stage III-IVb disease plus at least one high-risk feature, such as high Epstein Barr virus DNA titers. The majority of patients in both arms had three or more high risk features.
Over 80% of capecitabine subjects completed all eight cycles of treatment.
At a median follow-up of 44.8 months, 3-year failure-free survival was 87.7% with capecitabine vs. 73.3% in the control arm (HR .52, P = .037). Three-year overall survival was 92.6% with capecitabine vs. 88.9% with observation, which wasn’t statistically significant.
The incidence of acute grade 3/4 adverse events was 57.8% with standard dose capecitabine. Rates of hand foot syndrome, mucositis, anemia, and other problems were substantially higher than with observation.
For high-risk patients unable to tolerate chemotherapy, adjuvant capecitabine is a “suitable alternative treatment option,” said lead investigator Jingjing Miao, MD, of the department of nasopharyngeal carcinoma at Sun Yat-sen University Cancer Center, Guangzhou, China.
The trials were funded by Sun Yat-sen University and others. The investigators had no disclosures. Dr. Loong is an adviser, speaker, and/or researcher for a number of companies, including Novartis, Pfizer, and Lilly.
FROM ASCO 2021
Cabozantinib gains ground for salvage in differentiated thyroid cancer
The vascular endothelial growth factor receptor 2 blocker cabozantinib prolonged progression-free survival in radioiodine-refractory differentiated thyroid cancer following progression on first-line VEGFR inhibitors in a phase 3 trial from cabozantinib maker, Exelixis.
After a median follow up of 6.2 months, the 125 subjects on cabozantinib 60 mg every day had not reached median progression-free survival, but among the 62 randomized to placebo, mPFS was only 1.9 months.
The results led the Food and Drug Administration to grant cabozantinib breakthrough therapy status for salvage after progression on lenvatinib or sorafenib, the two VEGFR inhibitors approved for first-line treatment in radioiodine refractory differentiated thyroid cancer. Cabozantinib already carries a first-line indication for progressive, metastatic medullary thyroid cancer.
“We were all so excited to have sorafenib and lenvatinib,” but patients need another option after they develop resistance. “Cabozantinib is positioned to be the next in line,” said lead investigator Marcia Brose, MD, PhD, a thyroid specialist and professor at the University of Pennsylvania, Philadelphia, who presented the findings at the American Society of Clinical Oncology Annual Meeting.
The trial discussant, medical oncologist Nicole Chau, MD, clinical associate professor at the University of British Columbia, Vancouver, said the results “support cabozantinib as a potential second- or third-line” option, but its impact on quality of life and financial toxicity “should be evaluated.”
Subjects in the trial – dubbed COSMIC-311 – had locally advanced or metastatic disease that had progressed during or after first-line VEGFR treatment, including about 40% with lenvatinib, almost 40% with sorafenib, and over 20% with both.
The median age in the study was 66 years, and 55% of the subjects were women. Bone and liver metastases were more common in the cabozantinib arm.
Promising results
The robust of mPFS benefit (hazard ratio, 0.22; P < .0001) held across subgroups. The mPFS in the placebo arm of 1.9 months demonstrates that “these patients [progress rapidly], so you have to be ready with the next thing in line” to start it quickly, Dr. Brose said.
Overall survival favored cabozantinib (HR, 0.54) but didn’t reach statistical significance perhaps because placebo patients were allowed to cross over to cabozantinib after progression.
The overall response rate was 15% with cabozantinib versus no responders with placebo, which also didn’t meet the study’s criteria for clinical significance. Even so, the disease control rate of 60% with cabozantinib versus 27% with placebo, “is clinically meaningful in this heavily pretreated population,” Dr. Chau said.
Adverse events
Safety was consistent with previous reports and included diarrhea in 51% of cabozantinib subjects, hand-foot skin reaction in 46%, hypertension in 28%, fatigue in 27%, and nausea in 24%, all substantially higher than with placebo. Over half of cabozantinib subjects had grade 3-4 adverse events versus 26% on placebo. There were no treatment related deaths.
Adverse events led to dose reductions or holds in the majority of cabozantinib subjects, but only 5% discontinued the drug; the number might have been higher with longer follow-up, Dr. Chau said.
Genotype-targeted therapy is an option for patients with fusion alterations, but whether it should come before or after VEGFR inhibition is unclear, Dr. Brose noted.
Biomarkers to help with such treatment decisions will become “increasingly important as we move beyond the era of single-agent” VEGFR inhibitors, Dr. Chau said.
The study was funded by cabozantinib maker Exelixis, and three investigators were employees. Dr. Brose disclosed research funding and honoraria from the company, and is an adviser. Dr. Chau has no involvement with Exelixis.
The vascular endothelial growth factor receptor 2 blocker cabozantinib prolonged progression-free survival in radioiodine-refractory differentiated thyroid cancer following progression on first-line VEGFR inhibitors in a phase 3 trial from cabozantinib maker, Exelixis.
After a median follow up of 6.2 months, the 125 subjects on cabozantinib 60 mg every day had not reached median progression-free survival, but among the 62 randomized to placebo, mPFS was only 1.9 months.
The results led the Food and Drug Administration to grant cabozantinib breakthrough therapy status for salvage after progression on lenvatinib or sorafenib, the two VEGFR inhibitors approved for first-line treatment in radioiodine refractory differentiated thyroid cancer. Cabozantinib already carries a first-line indication for progressive, metastatic medullary thyroid cancer.
“We were all so excited to have sorafenib and lenvatinib,” but patients need another option after they develop resistance. “Cabozantinib is positioned to be the next in line,” said lead investigator Marcia Brose, MD, PhD, a thyroid specialist and professor at the University of Pennsylvania, Philadelphia, who presented the findings at the American Society of Clinical Oncology Annual Meeting.
The trial discussant, medical oncologist Nicole Chau, MD, clinical associate professor at the University of British Columbia, Vancouver, said the results “support cabozantinib as a potential second- or third-line” option, but its impact on quality of life and financial toxicity “should be evaluated.”
Subjects in the trial – dubbed COSMIC-311 – had locally advanced or metastatic disease that had progressed during or after first-line VEGFR treatment, including about 40% with lenvatinib, almost 40% with sorafenib, and over 20% with both.
The median age in the study was 66 years, and 55% of the subjects were women. Bone and liver metastases were more common in the cabozantinib arm.
Promising results
The robust of mPFS benefit (hazard ratio, 0.22; P < .0001) held across subgroups. The mPFS in the placebo arm of 1.9 months demonstrates that “these patients [progress rapidly], so you have to be ready with the next thing in line” to start it quickly, Dr. Brose said.
Overall survival favored cabozantinib (HR, 0.54) but didn’t reach statistical significance perhaps because placebo patients were allowed to cross over to cabozantinib after progression.
The overall response rate was 15% with cabozantinib versus no responders with placebo, which also didn’t meet the study’s criteria for clinical significance. Even so, the disease control rate of 60% with cabozantinib versus 27% with placebo, “is clinically meaningful in this heavily pretreated population,” Dr. Chau said.
Adverse events
Safety was consistent with previous reports and included diarrhea in 51% of cabozantinib subjects, hand-foot skin reaction in 46%, hypertension in 28%, fatigue in 27%, and nausea in 24%, all substantially higher than with placebo. Over half of cabozantinib subjects had grade 3-4 adverse events versus 26% on placebo. There were no treatment related deaths.
Adverse events led to dose reductions or holds in the majority of cabozantinib subjects, but only 5% discontinued the drug; the number might have been higher with longer follow-up, Dr. Chau said.
Genotype-targeted therapy is an option for patients with fusion alterations, but whether it should come before or after VEGFR inhibition is unclear, Dr. Brose noted.
Biomarkers to help with such treatment decisions will become “increasingly important as we move beyond the era of single-agent” VEGFR inhibitors, Dr. Chau said.
The study was funded by cabozantinib maker Exelixis, and three investigators were employees. Dr. Brose disclosed research funding and honoraria from the company, and is an adviser. Dr. Chau has no involvement with Exelixis.
The vascular endothelial growth factor receptor 2 blocker cabozantinib prolonged progression-free survival in radioiodine-refractory differentiated thyroid cancer following progression on first-line VEGFR inhibitors in a phase 3 trial from cabozantinib maker, Exelixis.
After a median follow up of 6.2 months, the 125 subjects on cabozantinib 60 mg every day had not reached median progression-free survival, but among the 62 randomized to placebo, mPFS was only 1.9 months.
The results led the Food and Drug Administration to grant cabozantinib breakthrough therapy status for salvage after progression on lenvatinib or sorafenib, the two VEGFR inhibitors approved for first-line treatment in radioiodine refractory differentiated thyroid cancer. Cabozantinib already carries a first-line indication for progressive, metastatic medullary thyroid cancer.
“We were all so excited to have sorafenib and lenvatinib,” but patients need another option after they develop resistance. “Cabozantinib is positioned to be the next in line,” said lead investigator Marcia Brose, MD, PhD, a thyroid specialist and professor at the University of Pennsylvania, Philadelphia, who presented the findings at the American Society of Clinical Oncology Annual Meeting.
The trial discussant, medical oncologist Nicole Chau, MD, clinical associate professor at the University of British Columbia, Vancouver, said the results “support cabozantinib as a potential second- or third-line” option, but its impact on quality of life and financial toxicity “should be evaluated.”
Subjects in the trial – dubbed COSMIC-311 – had locally advanced or metastatic disease that had progressed during or after first-line VEGFR treatment, including about 40% with lenvatinib, almost 40% with sorafenib, and over 20% with both.
The median age in the study was 66 years, and 55% of the subjects were women. Bone and liver metastases were more common in the cabozantinib arm.
Promising results
The robust of mPFS benefit (hazard ratio, 0.22; P < .0001) held across subgroups. The mPFS in the placebo arm of 1.9 months demonstrates that “these patients [progress rapidly], so you have to be ready with the next thing in line” to start it quickly, Dr. Brose said.
Overall survival favored cabozantinib (HR, 0.54) but didn’t reach statistical significance perhaps because placebo patients were allowed to cross over to cabozantinib after progression.
The overall response rate was 15% with cabozantinib versus no responders with placebo, which also didn’t meet the study’s criteria for clinical significance. Even so, the disease control rate of 60% with cabozantinib versus 27% with placebo, “is clinically meaningful in this heavily pretreated population,” Dr. Chau said.
Adverse events
Safety was consistent with previous reports and included diarrhea in 51% of cabozantinib subjects, hand-foot skin reaction in 46%, hypertension in 28%, fatigue in 27%, and nausea in 24%, all substantially higher than with placebo. Over half of cabozantinib subjects had grade 3-4 adverse events versus 26% on placebo. There were no treatment related deaths.
Adverse events led to dose reductions or holds in the majority of cabozantinib subjects, but only 5% discontinued the drug; the number might have been higher with longer follow-up, Dr. Chau said.
Genotype-targeted therapy is an option for patients with fusion alterations, but whether it should come before or after VEGFR inhibition is unclear, Dr. Brose noted.
Biomarkers to help with such treatment decisions will become “increasingly important as we move beyond the era of single-agent” VEGFR inhibitors, Dr. Chau said.
The study was funded by cabozantinib maker Exelixis, and three investigators were employees. Dr. Brose disclosed research funding and honoraria from the company, and is an adviser. Dr. Chau has no involvement with Exelixis.
FROM ASCO 2021
New drug toripalimab improves survival in nasopharyngeal cancer
A new immunotherapy, toripalimab, has the potential to change practice in the treatment of nasopharyngeal carcinoma (NPC), say experts.
The drug is a monoclonal antibody that blocks programmed cell death protein 1 (PD-1), developed in China and recently approved there for the third-line treatment of NPC, among other indications. The U.S. Food and Drug Administration has granted it a breakthrough therapy designation for recurrent/metastatic NPC, as well as fast-track and orphan drug status for other tumor types.
New results show that when toripalimab was added onto chemotherapy with gemcitabine and cisplatin in the first line for recurrent or metastatic nasopharyngeal carcinoma, there was a significant improvement in both progression-free survival and overall survival.
The results come from the phase 3 trial dubbed JUPITER-02 and will be presented at the plenary session of the American Society of Clinical Oncology annual meeting this Sunday; some details were released earlier at a press briefing
The trial randomly assigned 146 patients to toripalimab and 143 to placebo on a background of gemcitabine and cisplatin, the current standard of care for recurrent/metastatic NPC.
Median progression-free survival (PFS) was 11.7 months with toripalimab vs. 8 months with placebo, a significant improvement (hazard ratio, 0.52; 95% confidence interval, 0.36-0.74. P = .0003). Overall survival was not mature at reporting but favored toripalimab with 25 deaths versus 39 in the placebo group, a 40% risk reduction (P = .0462).
The results “support the use of toripalimab in combination with [gemcitabine and cisplatin] as a new standard of care for first-line treatment of recurrent or metastatic nasopharyngeal carcinoma,” said lead investigator and medical oncologist Rui-Hua Xu, MD, PhD, of the Sun Yat-sen University Cancer Center in Guangzhou, China.
Potential to change practice
The significance of the study is that it used immunotherapy in the first-line setting for NPC instead of the second line where it’s frequently used today, commented Jared Weiss, MD, an associate professor of oncology and a head and neck cancer specialist at the University of North Carolina, Chapel Hill.
If FDA approves toripalimab for the indication, it “would change [first-line] standard of care to the triplet regimen,” he said in an interview.
The discussant for this presentation, Julie Gralow, MD, agreed. “This is one of the first studies in metastatic or recurrent NPC to show a benefit” for combining a PD-1 inhibitor with chemotherapy.
“With FDA approval, these findings should prove practice-changing,” said Dr. Gralow, a professor of breast medical oncology at the University of Washington, Seattle, and ASCO’s chief medical officer.
Toripalimab, dosed at 240 mg in the trial, or placebo were administered with gemcitabine and cisplatin every 3 weeks for up to 6 cycles, followed by toripalimab or placebo maintenance every 3 weeks until disease progression, intolerable toxicity, or completion of 2 years of treatment.
The overall response rate was 77.4% with toripalimab and 66.4% with placebo, and the median duration of response in the toripalimab group was 10 months vs. 5.7 months with placebo.
One-year PFS was 49.4% with toripalimab versus 27.9% with placebo; improved PFS was observed with toripalimab across PD-L1 subgroups.
Grade 3 or worse adverse events occurred in slightly less than 90% of both groups, with fatal adverse events occurring in slightly less than 3% in both.
Adverse events leading to discontinuation occurred in 7.5% of the study group and 4.9% on placebo. As expected with immunotherapy, immune-related adverse events such as hypothyroidism were more common with toripalimab (39.7% vs. 18.9%), as were grade 3 or worse immune-related adverse events (7.5% vs. 0.7%).
At interim analysis in May 2020, the median duration treatment was 39 weeks in the toripalimab group and 36 weeks in the placebo group.
The trial was conducted in China, Taiwan, and Singapore.
JUPITER-02 was funded by Shanghai Junshi Bioscience. Investigator disclosures weren’t reported. Dr. Weiss said he had no relevant disclosures. Dr. Gralow is an advisor for a number of companies, including Genentech, Novartis, and Roche.
A version of this article first appeared on Medscape.com.
A new immunotherapy, toripalimab, has the potential to change practice in the treatment of nasopharyngeal carcinoma (NPC), say experts.
The drug is a monoclonal antibody that blocks programmed cell death protein 1 (PD-1), developed in China and recently approved there for the third-line treatment of NPC, among other indications. The U.S. Food and Drug Administration has granted it a breakthrough therapy designation for recurrent/metastatic NPC, as well as fast-track and orphan drug status for other tumor types.
New results show that when toripalimab was added onto chemotherapy with gemcitabine and cisplatin in the first line for recurrent or metastatic nasopharyngeal carcinoma, there was a significant improvement in both progression-free survival and overall survival.
The results come from the phase 3 trial dubbed JUPITER-02 and will be presented at the plenary session of the American Society of Clinical Oncology annual meeting this Sunday; some details were released earlier at a press briefing
The trial randomly assigned 146 patients to toripalimab and 143 to placebo on a background of gemcitabine and cisplatin, the current standard of care for recurrent/metastatic NPC.
Median progression-free survival (PFS) was 11.7 months with toripalimab vs. 8 months with placebo, a significant improvement (hazard ratio, 0.52; 95% confidence interval, 0.36-0.74. P = .0003). Overall survival was not mature at reporting but favored toripalimab with 25 deaths versus 39 in the placebo group, a 40% risk reduction (P = .0462).
The results “support the use of toripalimab in combination with [gemcitabine and cisplatin] as a new standard of care for first-line treatment of recurrent or metastatic nasopharyngeal carcinoma,” said lead investigator and medical oncologist Rui-Hua Xu, MD, PhD, of the Sun Yat-sen University Cancer Center in Guangzhou, China.
Potential to change practice
The significance of the study is that it used immunotherapy in the first-line setting for NPC instead of the second line where it’s frequently used today, commented Jared Weiss, MD, an associate professor of oncology and a head and neck cancer specialist at the University of North Carolina, Chapel Hill.
If FDA approves toripalimab for the indication, it “would change [first-line] standard of care to the triplet regimen,” he said in an interview.
The discussant for this presentation, Julie Gralow, MD, agreed. “This is one of the first studies in metastatic or recurrent NPC to show a benefit” for combining a PD-1 inhibitor with chemotherapy.
“With FDA approval, these findings should prove practice-changing,” said Dr. Gralow, a professor of breast medical oncology at the University of Washington, Seattle, and ASCO’s chief medical officer.
Toripalimab, dosed at 240 mg in the trial, or placebo were administered with gemcitabine and cisplatin every 3 weeks for up to 6 cycles, followed by toripalimab or placebo maintenance every 3 weeks until disease progression, intolerable toxicity, or completion of 2 years of treatment.
The overall response rate was 77.4% with toripalimab and 66.4% with placebo, and the median duration of response in the toripalimab group was 10 months vs. 5.7 months with placebo.
One-year PFS was 49.4% with toripalimab versus 27.9% with placebo; improved PFS was observed with toripalimab across PD-L1 subgroups.
Grade 3 or worse adverse events occurred in slightly less than 90% of both groups, with fatal adverse events occurring in slightly less than 3% in both.
Adverse events leading to discontinuation occurred in 7.5% of the study group and 4.9% on placebo. As expected with immunotherapy, immune-related adverse events such as hypothyroidism were more common with toripalimab (39.7% vs. 18.9%), as were grade 3 or worse immune-related adverse events (7.5% vs. 0.7%).
At interim analysis in May 2020, the median duration treatment was 39 weeks in the toripalimab group and 36 weeks in the placebo group.
The trial was conducted in China, Taiwan, and Singapore.
JUPITER-02 was funded by Shanghai Junshi Bioscience. Investigator disclosures weren’t reported. Dr. Weiss said he had no relevant disclosures. Dr. Gralow is an advisor for a number of companies, including Genentech, Novartis, and Roche.
A version of this article first appeared on Medscape.com.
A new immunotherapy, toripalimab, has the potential to change practice in the treatment of nasopharyngeal carcinoma (NPC), say experts.
The drug is a monoclonal antibody that blocks programmed cell death protein 1 (PD-1), developed in China and recently approved there for the third-line treatment of NPC, among other indications. The U.S. Food and Drug Administration has granted it a breakthrough therapy designation for recurrent/metastatic NPC, as well as fast-track and orphan drug status for other tumor types.
New results show that when toripalimab was added onto chemotherapy with gemcitabine and cisplatin in the first line for recurrent or metastatic nasopharyngeal carcinoma, there was a significant improvement in both progression-free survival and overall survival.
The results come from the phase 3 trial dubbed JUPITER-02 and will be presented at the plenary session of the American Society of Clinical Oncology annual meeting this Sunday; some details were released earlier at a press briefing
The trial randomly assigned 146 patients to toripalimab and 143 to placebo on a background of gemcitabine and cisplatin, the current standard of care for recurrent/metastatic NPC.
Median progression-free survival (PFS) was 11.7 months with toripalimab vs. 8 months with placebo, a significant improvement (hazard ratio, 0.52; 95% confidence interval, 0.36-0.74. P = .0003). Overall survival was not mature at reporting but favored toripalimab with 25 deaths versus 39 in the placebo group, a 40% risk reduction (P = .0462).
The results “support the use of toripalimab in combination with [gemcitabine and cisplatin] as a new standard of care for first-line treatment of recurrent or metastatic nasopharyngeal carcinoma,” said lead investigator and medical oncologist Rui-Hua Xu, MD, PhD, of the Sun Yat-sen University Cancer Center in Guangzhou, China.
Potential to change practice
The significance of the study is that it used immunotherapy in the first-line setting for NPC instead of the second line where it’s frequently used today, commented Jared Weiss, MD, an associate professor of oncology and a head and neck cancer specialist at the University of North Carolina, Chapel Hill.
If FDA approves toripalimab for the indication, it “would change [first-line] standard of care to the triplet regimen,” he said in an interview.
The discussant for this presentation, Julie Gralow, MD, agreed. “This is one of the first studies in metastatic or recurrent NPC to show a benefit” for combining a PD-1 inhibitor with chemotherapy.
“With FDA approval, these findings should prove practice-changing,” said Dr. Gralow, a professor of breast medical oncology at the University of Washington, Seattle, and ASCO’s chief medical officer.
Toripalimab, dosed at 240 mg in the trial, or placebo were administered with gemcitabine and cisplatin every 3 weeks for up to 6 cycles, followed by toripalimab or placebo maintenance every 3 weeks until disease progression, intolerable toxicity, or completion of 2 years of treatment.
The overall response rate was 77.4% with toripalimab and 66.4% with placebo, and the median duration of response in the toripalimab group was 10 months vs. 5.7 months with placebo.
One-year PFS was 49.4% with toripalimab versus 27.9% with placebo; improved PFS was observed with toripalimab across PD-L1 subgroups.
Grade 3 or worse adverse events occurred in slightly less than 90% of both groups, with fatal adverse events occurring in slightly less than 3% in both.
Adverse events leading to discontinuation occurred in 7.5% of the study group and 4.9% on placebo. As expected with immunotherapy, immune-related adverse events such as hypothyroidism were more common with toripalimab (39.7% vs. 18.9%), as were grade 3 or worse immune-related adverse events (7.5% vs. 0.7%).
At interim analysis in May 2020, the median duration treatment was 39 weeks in the toripalimab group and 36 weeks in the placebo group.
The trial was conducted in China, Taiwan, and Singapore.
JUPITER-02 was funded by Shanghai Junshi Bioscience. Investigator disclosures weren’t reported. Dr. Weiss said he had no relevant disclosures. Dr. Gralow is an advisor for a number of companies, including Genentech, Novartis, and Roche.
A version of this article first appeared on Medscape.com.