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HER2 status differed between primary tumor and CTCs in 18.8% of women with MBC
Discordance in HER2 status between the primary breast tumor and circulating tumor cells (CTCs) in women with HER2-negative metastatic disease was 18.8% in a prospective cohort of patients.
The probability of discordance decreased with increasing age but increased with primary tumors that were hormone-receptor positive, higher grade, and of lobular histology, Amelie De Gregorio, MD, and associates reported in JCO Precision Oncology.
The investigators evaluated the HER2 status of CTCs obtained from women with HER2-negative breast cancer screened in the ongoing German DETECT III trial, which is aimed at determining the efficacy of lapatinib in patients with initially HER2-negative metastatic breast cancer but HER2-positive CTCs. HER2 discordance was defined as the presence of a single CTC or more within 7.5 mL of peripheral blood that showed a strong immunohistochemical (IHC) staining intensity (IHC score 3+).
Out of 1,123 women screened, at least one CTC was detected in blood samples from 711 women (63.3%; 95% confidence interval, 60.4%-66.1%). The median number of CTCs detected was seven (interquartile range, 2-30; range, 1-35,078 CTCs), and discordance in HER2 phenotype between primary tumor and CTCs was found in 134 patients (18.8%), Dr. De Gregorio of University Hospital Ulm (Germany) and associates reported (JCO Precis Oncol. 2017 Sep 28. doi: 10.1200/PO.17.00023).
In a multivariable analysis, histologic type (lobular vs. ductal; odds ratio, 2.67; P less than .001), hormone receptor status (positive vs. negative; OR, 2.84; P = .024), and CTC number (greater than 5 vs. 1-4 CTCs; OR, 7.64; P less than .001) significantly and independently predicted discordance in HER2 phenotype between primary tumor and CTCs. There was also a significant effect of age, with the probability of discordance decreasing with increasing age, the investigators noted.
“The knowledge of factors associated with discordance in HER2 status may be incorporated into today’s clinical practice by guiding the decision process for performing biopsy to characterize metastatic relapse,” the investigators wrote.
“Moreover, the concept of liquid biopsy using CTCs as a real-time noninvasive monitoring tool to evaluate tumor biology, progression, and heterogeneity as a basis for more personalized treatment decisions should be tested in prospective randomized clinical trials,” they added.
The DETECT study program is supported by the Investigator-Initiated Study Program of Janssen Diagnostics, with clinical trials also supported by Pierre Fabre Pharma, TEVA Pharmaceuticals Industries, Amgen, Novartis Pharma, and Eisai. Dr. De Gregorio disclosed an advisory role with Roche Pharma AG; several coauthors disclosed consultancy and funding from various pharmaceutical companies.
[email protected]
On Twitter @nikolaideslaura
Discordance in HER2 status between the primary breast tumor and circulating tumor cells (CTCs) in women with HER2-negative metastatic disease was 18.8% in a prospective cohort of patients.
The probability of discordance decreased with increasing age but increased with primary tumors that were hormone-receptor positive, higher grade, and of lobular histology, Amelie De Gregorio, MD, and associates reported in JCO Precision Oncology.
The investigators evaluated the HER2 status of CTCs obtained from women with HER2-negative breast cancer screened in the ongoing German DETECT III trial, which is aimed at determining the efficacy of lapatinib in patients with initially HER2-negative metastatic breast cancer but HER2-positive CTCs. HER2 discordance was defined as the presence of a single CTC or more within 7.5 mL of peripheral blood that showed a strong immunohistochemical (IHC) staining intensity (IHC score 3+).
Out of 1,123 women screened, at least one CTC was detected in blood samples from 711 women (63.3%; 95% confidence interval, 60.4%-66.1%). The median number of CTCs detected was seven (interquartile range, 2-30; range, 1-35,078 CTCs), and discordance in HER2 phenotype between primary tumor and CTCs was found in 134 patients (18.8%), Dr. De Gregorio of University Hospital Ulm (Germany) and associates reported (JCO Precis Oncol. 2017 Sep 28. doi: 10.1200/PO.17.00023).
In a multivariable analysis, histologic type (lobular vs. ductal; odds ratio, 2.67; P less than .001), hormone receptor status (positive vs. negative; OR, 2.84; P = .024), and CTC number (greater than 5 vs. 1-4 CTCs; OR, 7.64; P less than .001) significantly and independently predicted discordance in HER2 phenotype between primary tumor and CTCs. There was also a significant effect of age, with the probability of discordance decreasing with increasing age, the investigators noted.
“The knowledge of factors associated with discordance in HER2 status may be incorporated into today’s clinical practice by guiding the decision process for performing biopsy to characterize metastatic relapse,” the investigators wrote.
“Moreover, the concept of liquid biopsy using CTCs as a real-time noninvasive monitoring tool to evaluate tumor biology, progression, and heterogeneity as a basis for more personalized treatment decisions should be tested in prospective randomized clinical trials,” they added.
The DETECT study program is supported by the Investigator-Initiated Study Program of Janssen Diagnostics, with clinical trials also supported by Pierre Fabre Pharma, TEVA Pharmaceuticals Industries, Amgen, Novartis Pharma, and Eisai. Dr. De Gregorio disclosed an advisory role with Roche Pharma AG; several coauthors disclosed consultancy and funding from various pharmaceutical companies.
[email protected]
On Twitter @nikolaideslaura
Discordance in HER2 status between the primary breast tumor and circulating tumor cells (CTCs) in women with HER2-negative metastatic disease was 18.8% in a prospective cohort of patients.
The probability of discordance decreased with increasing age but increased with primary tumors that were hormone-receptor positive, higher grade, and of lobular histology, Amelie De Gregorio, MD, and associates reported in JCO Precision Oncology.
The investigators evaluated the HER2 status of CTCs obtained from women with HER2-negative breast cancer screened in the ongoing German DETECT III trial, which is aimed at determining the efficacy of lapatinib in patients with initially HER2-negative metastatic breast cancer but HER2-positive CTCs. HER2 discordance was defined as the presence of a single CTC or more within 7.5 mL of peripheral blood that showed a strong immunohistochemical (IHC) staining intensity (IHC score 3+).
Out of 1,123 women screened, at least one CTC was detected in blood samples from 711 women (63.3%; 95% confidence interval, 60.4%-66.1%). The median number of CTCs detected was seven (interquartile range, 2-30; range, 1-35,078 CTCs), and discordance in HER2 phenotype between primary tumor and CTCs was found in 134 patients (18.8%), Dr. De Gregorio of University Hospital Ulm (Germany) and associates reported (JCO Precis Oncol. 2017 Sep 28. doi: 10.1200/PO.17.00023).
In a multivariable analysis, histologic type (lobular vs. ductal; odds ratio, 2.67; P less than .001), hormone receptor status (positive vs. negative; OR, 2.84; P = .024), and CTC number (greater than 5 vs. 1-4 CTCs; OR, 7.64; P less than .001) significantly and independently predicted discordance in HER2 phenotype between primary tumor and CTCs. There was also a significant effect of age, with the probability of discordance decreasing with increasing age, the investigators noted.
“The knowledge of factors associated with discordance in HER2 status may be incorporated into today’s clinical practice by guiding the decision process for performing biopsy to characterize metastatic relapse,” the investigators wrote.
“Moreover, the concept of liquid biopsy using CTCs as a real-time noninvasive monitoring tool to evaluate tumor biology, progression, and heterogeneity as a basis for more personalized treatment decisions should be tested in prospective randomized clinical trials,” they added.
The DETECT study program is supported by the Investigator-Initiated Study Program of Janssen Diagnostics, with clinical trials also supported by Pierre Fabre Pharma, TEVA Pharmaceuticals Industries, Amgen, Novartis Pharma, and Eisai. Dr. De Gregorio disclosed an advisory role with Roche Pharma AG; several coauthors disclosed consultancy and funding from various pharmaceutical companies.
[email protected]
On Twitter @nikolaideslaura
FROM JCO PRECISION ONCOLOGY
Key clinical point:
Major finding: Histologic type (lobular vs. ductal; odds ratio, 2.67; P less than .001), hormone receptor status (positive vs. negative; OR, 2.84; P = .024), and CTC number (more than 5 vs. 1-4 CTCs; OR, 7.64; P less than .001) significantly predicted HER2 discordance between primary tumor and CTCs.
Data source: A prospective cohort of 1,123 women with metastatic breast cancer screened for the ongoing DETECT III trial in Germany.
Disclosures: The DETECT study program is supported by the Investigator-Initiated Study Program of Janssen Diagnostics, with clinical trials also supported by Pierre Fabre Pharma, TEVA Pharmaceuticals Industries, Amgen, Novartis Pharma, and Eisai. Dr. De Gregorio disclosed an advisory role with Roche Pharma AG; several coauthors disclosed consultancy and funding from various pharaceutical companies.
FDA approves biosimilar to bevacizumab
The Food and Drug Administration has approved a biosimilar to bevacizumab (Avastin) for the treatment of certain colorectal, lung, brain, kidney, and cervical cancers.
Bevacizumab-awwb is the first biosimilar approved in the United States for the treatment of cancer, the FDA said in a press release.
Approval is based on structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrate bevacizumab-awwb is biosimilar to bevacizumab, the FDA said.
• Metastatic colorectal cancer, in combination with intravenous 5-fluorouracil-based chemotherapy for first- or second-line treatment.
• Metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan–based or fluoropyrimidine-oxaliplatin–based chemotherapy for the second-line treatment of patients who have progressed on a first-line bevacizumab product–containing regimen.
• Non-squamous non–small cell lung cancer, in combination with carboplatin and paclitaxel for first line treatment of unresectable, locally advanced, recurrent, or metastatic disease.
• Glioblastoma with progressive disease following prior therapy, based on improvement in objective response rate.
• Metastatic renal cell carcinoma, in combination with interferon alfa.
• Cervical cancer that is persistent, recurrent, or metastatic, in combination with paclitaxel and cisplatin or paclitaxel and topotecan.
Common expected side effects of the biosimilar include epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis.
Serious expected side effects include perforation or fistula, arterial and venous thromboembolic events, hypertension, posterior reversible encephalopathy syndrome, proteinuria, infusion-related reactions, and ovarian failure. Women who are pregnant should not take bevacizumab-awwb.
The biosimilar to bevacizumab carries a similar boxed warning regarding the increased risk of gastrointestinal perforations; surgery and wound healing complications; and severe or fatal pulmonary, gastrointestinal, central nervous system, and vaginal hemorrhage.
The biosimilar approval was granted to Amgen, which will market the drug under the trade name Mvasi.
The Food and Drug Administration has approved a biosimilar to bevacizumab (Avastin) for the treatment of certain colorectal, lung, brain, kidney, and cervical cancers.
Bevacizumab-awwb is the first biosimilar approved in the United States for the treatment of cancer, the FDA said in a press release.
Approval is based on structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrate bevacizumab-awwb is biosimilar to bevacizumab, the FDA said.
• Metastatic colorectal cancer, in combination with intravenous 5-fluorouracil-based chemotherapy for first- or second-line treatment.
• Metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan–based or fluoropyrimidine-oxaliplatin–based chemotherapy for the second-line treatment of patients who have progressed on a first-line bevacizumab product–containing regimen.
• Non-squamous non–small cell lung cancer, in combination with carboplatin and paclitaxel for first line treatment of unresectable, locally advanced, recurrent, or metastatic disease.
• Glioblastoma with progressive disease following prior therapy, based on improvement in objective response rate.
• Metastatic renal cell carcinoma, in combination with interferon alfa.
• Cervical cancer that is persistent, recurrent, or metastatic, in combination with paclitaxel and cisplatin or paclitaxel and topotecan.
Common expected side effects of the biosimilar include epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis.
Serious expected side effects include perforation or fistula, arterial and venous thromboembolic events, hypertension, posterior reversible encephalopathy syndrome, proteinuria, infusion-related reactions, and ovarian failure. Women who are pregnant should not take bevacizumab-awwb.
The biosimilar to bevacizumab carries a similar boxed warning regarding the increased risk of gastrointestinal perforations; surgery and wound healing complications; and severe or fatal pulmonary, gastrointestinal, central nervous system, and vaginal hemorrhage.
The biosimilar approval was granted to Amgen, which will market the drug under the trade name Mvasi.
The Food and Drug Administration has approved a biosimilar to bevacizumab (Avastin) for the treatment of certain colorectal, lung, brain, kidney, and cervical cancers.
Bevacizumab-awwb is the first biosimilar approved in the United States for the treatment of cancer, the FDA said in a press release.
Approval is based on structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrate bevacizumab-awwb is biosimilar to bevacizumab, the FDA said.
• Metastatic colorectal cancer, in combination with intravenous 5-fluorouracil-based chemotherapy for first- or second-line treatment.
• Metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan–based or fluoropyrimidine-oxaliplatin–based chemotherapy for the second-line treatment of patients who have progressed on a first-line bevacizumab product–containing regimen.
• Non-squamous non–small cell lung cancer, in combination with carboplatin and paclitaxel for first line treatment of unresectable, locally advanced, recurrent, or metastatic disease.
• Glioblastoma with progressive disease following prior therapy, based on improvement in objective response rate.
• Metastatic renal cell carcinoma, in combination with interferon alfa.
• Cervical cancer that is persistent, recurrent, or metastatic, in combination with paclitaxel and cisplatin or paclitaxel and topotecan.
Common expected side effects of the biosimilar include epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis.
Serious expected side effects include perforation or fistula, arterial and venous thromboembolic events, hypertension, posterior reversible encephalopathy syndrome, proteinuria, infusion-related reactions, and ovarian failure. Women who are pregnant should not take bevacizumab-awwb.
The biosimilar to bevacizumab carries a similar boxed warning regarding the increased risk of gastrointestinal perforations; surgery and wound healing complications; and severe or fatal pulmonary, gastrointestinal, central nervous system, and vaginal hemorrhage.
The biosimilar approval was granted to Amgen, which will market the drug under the trade name Mvasi.
ASCO issues guideline on communication with patients
Recommendations for improved communication between oncologists and their patients are the focus of a new guideline issued by a panel convened by the American Society of Clinical Oncology (ASCO).
The guideline recommends that oncologists establish care goals with each patient, address the costs of care, and initiate discussion of end-of-life preferences early in the course of incurable disease.
Patients also should be made aware of all treatment options, which may include clinical trials and, for certain patients, palliative care alone, the panel recommended.
The ASCO Expert Panel included medical oncologists, psychiatrists, nurses, and experts in hospice and palliative medicine, communication skills, health disparities, and advocacy. Their consensus-based, patient-clinician communication guideline drew on the panel’s systematic evaluation of guidelines, reviews and meta-analyses, and randomized, controlled trials published from 2006 through Oct. 1, 2016.
More specifics on the guideline are available here and feedback can be provided at asco.org/guidelineswiki.
Dr. Gilligan of the Taussig Cancer Institute and the Center for Excellence in Healthcare Communication, Cleveland Clinic, disclosed support from WellPoint; other panel members disclosed various consultancy roles or funding from pharmaceutical companies and CVS Health.
[email protected]
On Twitter @NikolaidesLaura
Recommendations for improved communication between oncologists and their patients are the focus of a new guideline issued by a panel convened by the American Society of Clinical Oncology (ASCO).
The guideline recommends that oncologists establish care goals with each patient, address the costs of care, and initiate discussion of end-of-life preferences early in the course of incurable disease.
Patients also should be made aware of all treatment options, which may include clinical trials and, for certain patients, palliative care alone, the panel recommended.
The ASCO Expert Panel included medical oncologists, psychiatrists, nurses, and experts in hospice and palliative medicine, communication skills, health disparities, and advocacy. Their consensus-based, patient-clinician communication guideline drew on the panel’s systematic evaluation of guidelines, reviews and meta-analyses, and randomized, controlled trials published from 2006 through Oct. 1, 2016.
More specifics on the guideline are available here and feedback can be provided at asco.org/guidelineswiki.
Dr. Gilligan of the Taussig Cancer Institute and the Center for Excellence in Healthcare Communication, Cleveland Clinic, disclosed support from WellPoint; other panel members disclosed various consultancy roles or funding from pharmaceutical companies and CVS Health.
[email protected]
On Twitter @NikolaidesLaura
Recommendations for improved communication between oncologists and their patients are the focus of a new guideline issued by a panel convened by the American Society of Clinical Oncology (ASCO).
The guideline recommends that oncologists establish care goals with each patient, address the costs of care, and initiate discussion of end-of-life preferences early in the course of incurable disease.
Patients also should be made aware of all treatment options, which may include clinical trials and, for certain patients, palliative care alone, the panel recommended.
The ASCO Expert Panel included medical oncologists, psychiatrists, nurses, and experts in hospice and palliative medicine, communication skills, health disparities, and advocacy. Their consensus-based, patient-clinician communication guideline drew on the panel’s systematic evaluation of guidelines, reviews and meta-analyses, and randomized, controlled trials published from 2006 through Oct. 1, 2016.
More specifics on the guideline are available here and feedback can be provided at asco.org/guidelineswiki.
Dr. Gilligan of the Taussig Cancer Institute and the Center for Excellence in Healthcare Communication, Cleveland Clinic, disclosed support from WellPoint; other panel members disclosed various consultancy roles or funding from pharmaceutical companies and CVS Health.
[email protected]
On Twitter @NikolaidesLaura
FDA advisory committee to consider adjuvant sunitinib for RCC
The Oncologic Drugs Advisory Committee to the Food and Drug Administration will meet on Sept. 19 to discuss a supplemental new drug application for sunitinib (Sutent), for the adjuvant treatment of adult patients at high risk of recurrent renal cell carcinoma (RCC) following nephrectomy.
Sunitinib is an oral antiangiogenic agent that has been approved for the treatment of advanced RCC since 2006.
The FDA accepted the new drug application in May and is expected to issue a decision by January 2018.
Results for sunitinib as adjuvant treatment have been mixed. No significant differences in disease-free survival or overall survival were found in the phase 3 ASSURE between patients receiving adjuvant sunitinib and those receiving placebo, according to results published in The Lancet. However, adjuvant sunitinib prolonged disease-free survival by 1.2 years, compared with placebo, in the phase 3 S-TRAC trial, presented at the 2016 ESMO Congress and published in the New England Journal of Medicine. S-TRAC results are the basis for the new drug application submitted by Pfizer, Inc., according to a press release.
The advisory committee will consider comments from the public if submitted by Sept. 5, as electronic comments through the electronic filing system or by mail/hand delivery/courier at Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
The docket number is FDA-2017-N-1063.
The Oncologic Drugs Advisory Committee to the Food and Drug Administration will meet on Sept. 19 to discuss a supplemental new drug application for sunitinib (Sutent), for the adjuvant treatment of adult patients at high risk of recurrent renal cell carcinoma (RCC) following nephrectomy.
Sunitinib is an oral antiangiogenic agent that has been approved for the treatment of advanced RCC since 2006.
The FDA accepted the new drug application in May and is expected to issue a decision by January 2018.
Results for sunitinib as adjuvant treatment have been mixed. No significant differences in disease-free survival or overall survival were found in the phase 3 ASSURE between patients receiving adjuvant sunitinib and those receiving placebo, according to results published in The Lancet. However, adjuvant sunitinib prolonged disease-free survival by 1.2 years, compared with placebo, in the phase 3 S-TRAC trial, presented at the 2016 ESMO Congress and published in the New England Journal of Medicine. S-TRAC results are the basis for the new drug application submitted by Pfizer, Inc., according to a press release.
The advisory committee will consider comments from the public if submitted by Sept. 5, as electronic comments through the electronic filing system or by mail/hand delivery/courier at Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
The docket number is FDA-2017-N-1063.
The Oncologic Drugs Advisory Committee to the Food and Drug Administration will meet on Sept. 19 to discuss a supplemental new drug application for sunitinib (Sutent), for the adjuvant treatment of adult patients at high risk of recurrent renal cell carcinoma (RCC) following nephrectomy.
Sunitinib is an oral antiangiogenic agent that has been approved for the treatment of advanced RCC since 2006.
The FDA accepted the new drug application in May and is expected to issue a decision by January 2018.
Results for sunitinib as adjuvant treatment have been mixed. No significant differences in disease-free survival or overall survival were found in the phase 3 ASSURE between patients receiving adjuvant sunitinib and those receiving placebo, according to results published in The Lancet. However, adjuvant sunitinib prolonged disease-free survival by 1.2 years, compared with placebo, in the phase 3 S-TRAC trial, presented at the 2016 ESMO Congress and published in the New England Journal of Medicine. S-TRAC results are the basis for the new drug application submitted by Pfizer, Inc., according to a press release.
The advisory committee will consider comments from the public if submitted by Sept. 5, as electronic comments through the electronic filing system or by mail/hand delivery/courier at Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
The docket number is FDA-2017-N-1063.
FDA approves nivolumab for metastatic CRC
The Food and Drug Administration has granted accelerated approval to checkpoint inhibitor nivolumab for the treatment of patients with mismatch repair deficient (dMMR) and microsatellite instability high (MSI-H) metastatic colorectal cancer (CRC) that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.
The indication covers patients aged 12 years and older. Efficacy for adolescent patients with MSI-H or dMMR metastatic CRC is extrapolated from the results in the respective adult population, the FDA said in a statement.
Approval of nivolumab in the adult population was based on an objective response rate of 28% in CHECKMATE 142, an open-label, single-arm study of 53 patients with locally determined dMMR or MSI-H metastatic CRC who had disease progression during, after, or were intolerant to prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
The most common adverse reactions to nivolumab, marketed as Opdivo by Bristol-Myers Squibb, include fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, and pyrexia, the FDA said.
The recommended nivolumab dose is 240 mg every 2 weeks.
The Food and Drug Administration has granted accelerated approval to checkpoint inhibitor nivolumab for the treatment of patients with mismatch repair deficient (dMMR) and microsatellite instability high (MSI-H) metastatic colorectal cancer (CRC) that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.
The indication covers patients aged 12 years and older. Efficacy for adolescent patients with MSI-H or dMMR metastatic CRC is extrapolated from the results in the respective adult population, the FDA said in a statement.
Approval of nivolumab in the adult population was based on an objective response rate of 28% in CHECKMATE 142, an open-label, single-arm study of 53 patients with locally determined dMMR or MSI-H metastatic CRC who had disease progression during, after, or were intolerant to prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
The most common adverse reactions to nivolumab, marketed as Opdivo by Bristol-Myers Squibb, include fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, and pyrexia, the FDA said.
The recommended nivolumab dose is 240 mg every 2 weeks.
The Food and Drug Administration has granted accelerated approval to checkpoint inhibitor nivolumab for the treatment of patients with mismatch repair deficient (dMMR) and microsatellite instability high (MSI-H) metastatic colorectal cancer (CRC) that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.
The indication covers patients aged 12 years and older. Efficacy for adolescent patients with MSI-H or dMMR metastatic CRC is extrapolated from the results in the respective adult population, the FDA said in a statement.
Approval of nivolumab in the adult population was based on an objective response rate of 28% in CHECKMATE 142, an open-label, single-arm study of 53 patients with locally determined dMMR or MSI-H metastatic CRC who had disease progression during, after, or were intolerant to prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
The most common adverse reactions to nivolumab, marketed as Opdivo by Bristol-Myers Squibb, include fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, and pyrexia, the FDA said.
The recommended nivolumab dose is 240 mg every 2 weeks.
FDA grants priority review of acalabrutinib for second-line treatment of MCL
The Food and Drug Administration has granted a priority review for acalabrutinib, a Bruton tyrosine kinase inhibitor, for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
The new drug application is based on results from the phase 2 ACE-LY-004 trial, which evaluated the safety and efficacy of acalabrutinib in patients with relapsed/refractory MCL who had received at least one prior therapy.
[email protected]
On Twitter @NikolaidesLaura
The Food and Drug Administration has granted a priority review for acalabrutinib, a Bruton tyrosine kinase inhibitor, for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
The new drug application is based on results from the phase 2 ACE-LY-004 trial, which evaluated the safety and efficacy of acalabrutinib in patients with relapsed/refractory MCL who had received at least one prior therapy.
[email protected]
On Twitter @NikolaidesLaura
The Food and Drug Administration has granted a priority review for acalabrutinib, a Bruton tyrosine kinase inhibitor, for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
The new drug application is based on results from the phase 2 ACE-LY-004 trial, which evaluated the safety and efficacy of acalabrutinib in patients with relapsed/refractory MCL who had received at least one prior therapy.
[email protected]
On Twitter @NikolaidesLaura
FDA approves neratinib for extended adjuvant treatment of HER2+ breast cancer
The Food and Drug Administration has approved neratinib, an oral tyrosine kinase inhibitor, for the extended adjuvant treatment of patients with early-stage, HER2-positive breast cancer who have previously been treated with trastuzumab.
Approval was based on improved invasive disease-free survival (iDFS) in the phase 3 ExteNET trial of 2,840 women with early-stage HER2-positive breast cancer who were within 2 years of completing adjuvant trastuzumab. Patients were randomized to receive either neratinib or placebo daily for 1 year. After 2 years of follow-up, iDFS was 94.2% in patients treated with neratinib, compared with 91.9% in those receiving placebo (hazard ratio, 0.66; 95% confidence interval, 0.49, 0.90; P = .008), according to the FDA statement.
The most common adverse reactions to neratinib in ExteNET were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight loss, and urinary tract infection. Diarrhea was observed in 16.8% of neratinib-treated patients.
The recommended dose of of neratinib is 240 mg (six 40 mg tablets) given orally once daily with food, continuously, for 1 year. Patients should be given antidiarrheal prophylaxis for the first 56 days of treatment with neratinib and as needed thereafter to help manage diarrhea, the FDA said.
The Food and Drug Administration has approved neratinib, an oral tyrosine kinase inhibitor, for the extended adjuvant treatment of patients with early-stage, HER2-positive breast cancer who have previously been treated with trastuzumab.
Approval was based on improved invasive disease-free survival (iDFS) in the phase 3 ExteNET trial of 2,840 women with early-stage HER2-positive breast cancer who were within 2 years of completing adjuvant trastuzumab. Patients were randomized to receive either neratinib or placebo daily for 1 year. After 2 years of follow-up, iDFS was 94.2% in patients treated with neratinib, compared with 91.9% in those receiving placebo (hazard ratio, 0.66; 95% confidence interval, 0.49, 0.90; P = .008), according to the FDA statement.
The most common adverse reactions to neratinib in ExteNET were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight loss, and urinary tract infection. Diarrhea was observed in 16.8% of neratinib-treated patients.
The recommended dose of of neratinib is 240 mg (six 40 mg tablets) given orally once daily with food, continuously, for 1 year. Patients should be given antidiarrheal prophylaxis for the first 56 days of treatment with neratinib and as needed thereafter to help manage diarrhea, the FDA said.
The Food and Drug Administration has approved neratinib, an oral tyrosine kinase inhibitor, for the extended adjuvant treatment of patients with early-stage, HER2-positive breast cancer who have previously been treated with trastuzumab.
Approval was based on improved invasive disease-free survival (iDFS) in the phase 3 ExteNET trial of 2,840 women with early-stage HER2-positive breast cancer who were within 2 years of completing adjuvant trastuzumab. Patients were randomized to receive either neratinib or placebo daily for 1 year. After 2 years of follow-up, iDFS was 94.2% in patients treated with neratinib, compared with 91.9% in those receiving placebo (hazard ratio, 0.66; 95% confidence interval, 0.49, 0.90; P = .008), according to the FDA statement.
The most common adverse reactions to neratinib in ExteNET were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight loss, and urinary tract infection. Diarrhea was observed in 16.8% of neratinib-treated patients.
The recommended dose of of neratinib is 240 mg (six 40 mg tablets) given orally once daily with food, continuously, for 1 year. Patients should be given antidiarrheal prophylaxis for the first 56 days of treatment with neratinib and as needed thereafter to help manage diarrhea, the FDA said.
FDA approves dabrafenib and trametinib for BRAF V600E+ metastatic NSCLC
The FDA also approved a diagnostic, the Oncomine Dx Target Test, a next-generation sequencing test to detect gene mutations or alterations, including BRAF, from a single tissue specimen, the FDA reported in a statement.
The approvals are based on overall response rate (ORR) for the combination in a phase II, nonrandomized, noncomparative, open-label trial of patients with locally confirmed BRAF V600E mutation-positive metastatic NSCLC. The ORR for the combination treatment was 61% (95% confidence interval, 44%-77%) among 36 patients who had received no prior systemic therapy for metastatic NSCLC, and 63% (95% CI, 49%-76%) among 57 patients who had received at least one platinum-based chemotherapy regimen with demonstrated disease progression before enrollment. Those 93 patients were all treated with the combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily).
The ORR was 27% (95% CI, 18%-38%) among a third cohort of 78 patients with previously treated BRAF V600E mutation-positive NSCLC who received single-agent dabrafenib.
The most common adverse reactions were similar to those reported in prior approvals for patients with melanoma, including pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea. The most common grade 3-4 adverse reactions were pyrexia, fatigue, dyspnea, vomiting, rash, hemorrhage, and diarrhea. The most common grade 3-4 laboratory abnormalities were hyponatremia, lymphopenia, anemia, hyperglycemia, neutropenia, leukopenia, hypophosphatemia, and increased alanine aminotransferase. Dabrafenib and trametinib were discontinued for adverse reactions in 18% and 19% of patients, respectively, the FDA said.
Novartis is marketing Dabrafenib as Tafinlar and trametinib as Mekinist.
The recommended doses are dabrafenib 150 mg orally twice daily, approximately 12 hours apart, with trametinib 2 mg orally once daily, following confirmation of BRAF V600E mutation in a tumor specimen by an FDA-approved test.
The FDA also approved a diagnostic, the Oncomine Dx Target Test, a next-generation sequencing test to detect gene mutations or alterations, including BRAF, from a single tissue specimen, the FDA reported in a statement.
The approvals are based on overall response rate (ORR) for the combination in a phase II, nonrandomized, noncomparative, open-label trial of patients with locally confirmed BRAF V600E mutation-positive metastatic NSCLC. The ORR for the combination treatment was 61% (95% confidence interval, 44%-77%) among 36 patients who had received no prior systemic therapy for metastatic NSCLC, and 63% (95% CI, 49%-76%) among 57 patients who had received at least one platinum-based chemotherapy regimen with demonstrated disease progression before enrollment. Those 93 patients were all treated with the combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily).
The ORR was 27% (95% CI, 18%-38%) among a third cohort of 78 patients with previously treated BRAF V600E mutation-positive NSCLC who received single-agent dabrafenib.
The most common adverse reactions were similar to those reported in prior approvals for patients with melanoma, including pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea. The most common grade 3-4 adverse reactions were pyrexia, fatigue, dyspnea, vomiting, rash, hemorrhage, and diarrhea. The most common grade 3-4 laboratory abnormalities were hyponatremia, lymphopenia, anemia, hyperglycemia, neutropenia, leukopenia, hypophosphatemia, and increased alanine aminotransferase. Dabrafenib and trametinib were discontinued for adverse reactions in 18% and 19% of patients, respectively, the FDA said.
Novartis is marketing Dabrafenib as Tafinlar and trametinib as Mekinist.
The recommended doses are dabrafenib 150 mg orally twice daily, approximately 12 hours apart, with trametinib 2 mg orally once daily, following confirmation of BRAF V600E mutation in a tumor specimen by an FDA-approved test.
The FDA also approved a diagnostic, the Oncomine Dx Target Test, a next-generation sequencing test to detect gene mutations or alterations, including BRAF, from a single tissue specimen, the FDA reported in a statement.
The approvals are based on overall response rate (ORR) for the combination in a phase II, nonrandomized, noncomparative, open-label trial of patients with locally confirmed BRAF V600E mutation-positive metastatic NSCLC. The ORR for the combination treatment was 61% (95% confidence interval, 44%-77%) among 36 patients who had received no prior systemic therapy for metastatic NSCLC, and 63% (95% CI, 49%-76%) among 57 patients who had received at least one platinum-based chemotherapy regimen with demonstrated disease progression before enrollment. Those 93 patients were all treated with the combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily).
The ORR was 27% (95% CI, 18%-38%) among a third cohort of 78 patients with previously treated BRAF V600E mutation-positive NSCLC who received single-agent dabrafenib.
The most common adverse reactions were similar to those reported in prior approvals for patients with melanoma, including pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea. The most common grade 3-4 adverse reactions were pyrexia, fatigue, dyspnea, vomiting, rash, hemorrhage, and diarrhea. The most common grade 3-4 laboratory abnormalities were hyponatremia, lymphopenia, anemia, hyperglycemia, neutropenia, leukopenia, hypophosphatemia, and increased alanine aminotransferase. Dabrafenib and trametinib were discontinued for adverse reactions in 18% and 19% of patients, respectively, the FDA said.
Novartis is marketing Dabrafenib as Tafinlar and trametinib as Mekinist.
The recommended doses are dabrafenib 150 mg orally twice daily, approximately 12 hours apart, with trametinib 2 mg orally once daily, following confirmation of BRAF V600E mutation in a tumor specimen by an FDA-approved test.
FDA approves rituximab + hyaluronidase human for FL, DLBCL, and CLL
The Food and Drug Administration has approved rituximab plus hyaluronidase human for adult patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL).
The combination product, to be marketed as Rituxan Hycela, is administered subcutaneously, shortening administration time to 5 to 7 minutes as compared with the several hours needed for intravenous infusion, the FDA said in a statement.
Approval was based on noninferior rituximab trough concentrations for the subcutaneously administered combination, compared with intravenous rituximab, and comparable efficacy and safety results as shown in multiple randomized clinical trials.
The most common adverse events seen with the combination in patients with FL included infections, neutropenia, nausea, constipation, cough, and fatigue. In patients with DLBCL, the most common adverse events were infections, neutropenia, alopecia, nausea, and anemia; in CLL patients, infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and injection site erythema occurred most commonly.
The combination is indicated for the following previously approved indications for rituximab:
- Relapsed or refractory FL as a single agent.
- Previously untreated FL in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy.
- Nonprogressing (including stable disease) FL as a single agent after first-line cyclophosphamide, vincristine, and prednisone chemotherapy.
- Previously untreated DLBCL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone or other anthracycline-based chemotherapy regimens.
- Previously untreated and previously treated CLL in combination with fludarabine and cyclophosphamide.
The recommended doses are 1,400 mg rituximab and 23,400 units hyaluronidase human for FL and DLBCL and 1,600 mg rituximab and 26,800 units hyaluronidase human for CLL. The combination treatment should be initiated only after patients have received at least one full dose of a rituximab product by intravenous infusion, according to the prescribing information.
Rituxan Hycela is marketed by Genentech.
The Food and Drug Administration has approved rituximab plus hyaluronidase human for adult patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL).
The combination product, to be marketed as Rituxan Hycela, is administered subcutaneously, shortening administration time to 5 to 7 minutes as compared with the several hours needed for intravenous infusion, the FDA said in a statement.
Approval was based on noninferior rituximab trough concentrations for the subcutaneously administered combination, compared with intravenous rituximab, and comparable efficacy and safety results as shown in multiple randomized clinical trials.
The most common adverse events seen with the combination in patients with FL included infections, neutropenia, nausea, constipation, cough, and fatigue. In patients with DLBCL, the most common adverse events were infections, neutropenia, alopecia, nausea, and anemia; in CLL patients, infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and injection site erythema occurred most commonly.
The combination is indicated for the following previously approved indications for rituximab:
- Relapsed or refractory FL as a single agent.
- Previously untreated FL in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy.
- Nonprogressing (including stable disease) FL as a single agent after first-line cyclophosphamide, vincristine, and prednisone chemotherapy.
- Previously untreated DLBCL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone or other anthracycline-based chemotherapy regimens.
- Previously untreated and previously treated CLL in combination with fludarabine and cyclophosphamide.
The recommended doses are 1,400 mg rituximab and 23,400 units hyaluronidase human for FL and DLBCL and 1,600 mg rituximab and 26,800 units hyaluronidase human for CLL. The combination treatment should be initiated only after patients have received at least one full dose of a rituximab product by intravenous infusion, according to the prescribing information.
Rituxan Hycela is marketed by Genentech.
The Food and Drug Administration has approved rituximab plus hyaluronidase human for adult patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL).
The combination product, to be marketed as Rituxan Hycela, is administered subcutaneously, shortening administration time to 5 to 7 minutes as compared with the several hours needed for intravenous infusion, the FDA said in a statement.
Approval was based on noninferior rituximab trough concentrations for the subcutaneously administered combination, compared with intravenous rituximab, and comparable efficacy and safety results as shown in multiple randomized clinical trials.
The most common adverse events seen with the combination in patients with FL included infections, neutropenia, nausea, constipation, cough, and fatigue. In patients with DLBCL, the most common adverse events were infections, neutropenia, alopecia, nausea, and anemia; in CLL patients, infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and injection site erythema occurred most commonly.
The combination is indicated for the following previously approved indications for rituximab:
- Relapsed or refractory FL as a single agent.
- Previously untreated FL in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy.
- Nonprogressing (including stable disease) FL as a single agent after first-line cyclophosphamide, vincristine, and prednisone chemotherapy.
- Previously untreated DLBCL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone or other anthracycline-based chemotherapy regimens.
- Previously untreated and previously treated CLL in combination with fludarabine and cyclophosphamide.
The recommended doses are 1,400 mg rituximab and 23,400 units hyaluronidase human for FL and DLBCL and 1,600 mg rituximab and 26,800 units hyaluronidase human for CLL. The combination treatment should be initiated only after patients have received at least one full dose of a rituximab product by intravenous infusion, according to the prescribing information.
Rituxan Hycela is marketed by Genentech.
VIDEO: Dr. William J. Gradishar shares breast cancer take-aways from ASCO 2017
CHICAGO – William J. Gradishar, MD, outlines key research on breast cancer treatment presented at the annual meeting of the American Society of Clinical Oncology.
In a video interview, Dr. Gradishar, the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, discusses the take-home messages on pertuzumab for HER2+ breast cancer, PARP inhibitors for BRCA-mutated breast cancer, and CDK4/6 inhibitors for ER+ breast cancers.
In another video interview, Katherine O’Brien of the Metastatic Breast Cancer Network provides the patient advocate view on this years’ meeting.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @NikolaidesLaura
CHICAGO – William J. Gradishar, MD, outlines key research on breast cancer treatment presented at the annual meeting of the American Society of Clinical Oncology.
In a video interview, Dr. Gradishar, the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, discusses the take-home messages on pertuzumab for HER2+ breast cancer, PARP inhibitors for BRCA-mutated breast cancer, and CDK4/6 inhibitors for ER+ breast cancers.
In another video interview, Katherine O’Brien of the Metastatic Breast Cancer Network provides the patient advocate view on this years’ meeting.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @NikolaidesLaura
CHICAGO – William J. Gradishar, MD, outlines key research on breast cancer treatment presented at the annual meeting of the American Society of Clinical Oncology.
In a video interview, Dr. Gradishar, the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, discusses the take-home messages on pertuzumab for HER2+ breast cancer, PARP inhibitors for BRCA-mutated breast cancer, and CDK4/6 inhibitors for ER+ breast cancers.
In another video interview, Katherine O’Brien of the Metastatic Breast Cancer Network provides the patient advocate view on this years’ meeting.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @NikolaidesLaura
EXPERT ANALYSIS FROM ASCO 2017
