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FDA Approvals in RCC and CML, Priority Review Designations in NSCLC and RCC, and More

Gina Columbus
Published: Friday, Dec 22, 2017



Today-

FDA approvals in renal cell carcinoma and chronic myeloma leukemia, priority review designations in non–small cell lung cancer and renal cell carcinoma, and European recommendations for melanoma, mantle cell lymphoma, and a biosimilar.

Welcome to OncLive News Network! I’m Gina Columbus.

The FDA has approved cabozantinib for previously untreated patients with advanced renal cell carcinoma, based on a meaningful improvement in progression-free survival versus sunitinib in the CABOSUN trial. The approval was granted approximately 2 months ahead of an FDA deadline.

In the phase II study, first-line treatment with cabozantinib reduced the risk of progression or death by 52% compared with sunitinib for patients with advanced disease. The median progression-free survival was 8.6 months with cabozantinib versus 5.3 months for sunitinib.

After 30.8 months of follow-up, the median overall survival was 26.6 months in the cabozantinib arm versus 21.2 months in the sunitinib arm, representing a nonstatistically significant 20% reduction in the risk of death.

Cabozantinib showed similar superiority to sunitinib across all prespecified patient subgroups, including risk, bone metastases, and MET status.

*****************************************

In chronic myeloma leukemia, the FDA has approved bosutinib as a first-line treatment for patients with Philadelphia chromosome-positive disease.

The decision was based on data from the open-label phase III BFORE trial, which compared bosutinib with standard of care imatinib.

Results showed that the major molecular response at 12 months was 47.2% with bosutinib versus 36.9% for imatinib. The complete cytogenetic response rate by 12 months was 77.2% with bosutinib compared with 66.4% for patients treated with imatinib.

Additionally, the 6-month MMR was 35.0% with bosutinib and 18.3% with imatinib, and the 9-month MMR was 42.3% for bosutinib and 29.5% for imatinib. The cumulative incidence function of MMR was more favorable with bosutinib, indicating a shorter time to response.

The approval is contingent upon findings from long-term follow up.

*****************************************

The FDA has granted a priority review to a supplemental new drug application for the use of osimertinib as a first-line treatment for patients with non–small cell lung cancer whose tumors harbor EGFR mutations, which include exon 19 deletions or exon 21 substitution mutations.

The application is based on the pivotal phase III FLAURA study, which demonstrated that frontline osimertinib reduced the risk of progression or death by 54% versus standard erlotinib or gefitinib. In the double-blind study, the median progression-free survival was 10.2 months for standard therapy and 18.9 months with osimertinib. The PFS benefit with osimertinib extended across all prespecified subgroups, including patients with CNS metastases.

Moreover, the objective response rate with osimertinib was 80% versus 76% for erlotinib and gefitinib. The median duration of response with osimertinib was 17.2 months versus 8.5 months in the comparator arm.

Under the priority review, the FDA acts within 6 months of receiving a supplemental application, rather than the standard 10 months.

******************************

In renal cell carcinoma, the FDA granted a priority review to a supplemental biologics license application for the combination of nivolumab and ipilimumab as a frontline treatment for intermediate- and poor-risk patients with advanced disease.

The application stems from results of the phase III CheckMate-214 trial, in which frontline treatment with the immunotherapy combination reduced the risk of death by 32% versus sunitinib for patients with metastatic disease.

Findings showed that the median overall survival was not reached with the combination versus 32.9 months with sunitinib. In those specifically with intermediate- and poor-risk RCC, the median OS was not reached in the nivolumab and ipilimumab arm and was 26.0 months in the sunitinib arm, representing a 37% reduction in the risk of death. In those with favorable-risk disease, there was not a benefit for the combination versus sunitinib.

The FDA is scheduled to make its final decision on the sBLA on or before April 16, 2018.

**************************************

The European Union’s Committee for Medicinal Products for Human Use has delivered a positive opinion for Herzuma, a trastuzumab biosimilar, for the treatment of patients with HER2-positive early breast cancer, metastatic breast cancer, or metastatic gastric cancer. The CHMP’s opinion will now go to the European Commission for final review.

A phase III equivalence trial evaluating Herzuma for safety and efficacy compared with trastuzumab showed that rates of pathologic complete response were similar between the treatment arms in the intent-to-treat population at 46.8% for Herzuma and 50.4% for trastuzumab. The estimated difference in pCR proportion between the 2 groups was –.04.

Regarding safety, the percentage of patients reporting treatment-emergent adverse events was 94% in the Herzuma group versus 95% with trastuzumab. Six percent of patients in the Herzuma group experienced grade 3 or higher treatment-emergent adverse events versus 8% in the trastuzumab group.

**************************************

In melanoma, the European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of ipilimumab for the treatment of pediatric patients aged 12 years and older with unresectable or metastatic disease.

According to Bristol-Meyers Squibb, the developer of ipilimumab, the CHMP recommendation is its first positive opinion for an immuno-oncology agent in the pediatric setting.

The application is based on data across 2 trials in which objective responses were observed in 2 of 17 patients aged more than 12 years with advanced melanoma. The responses included 1 partial response that lasted for 16 months.

The pivotal ipilimumab pediatric trials included a dose-finding study involving 33 patients aged 2 to 21 years with relapsed/refractory solid tumors, and a single-arm, open-label trial that accrued 12 patients aged 12 to 16 years with stage III or IV melanoma, either previously treated or untreated.

***********************************

The United Kingdom's National Institute for Health Care and Excellence has published new guidelines recommending ibrutinib as a treatment for patients with relapsed/refractory mantle cell lymphoma.

Ibrutinib is approved for patients who have undergone 1 previous line of therapy, and if Janssen Biotech, the drug’s manufacturer, provides ibrutinib with the discount agreed in the commercial access agreement with NHS England. The amount of the discount was not released.

Earlier this year, NICE said it could not recommend routine use of ibrutinib in MCL because it did not meet NHS requirements for value per QALY. Ibrutinib is currently available through the Cancer Drugs Fund.

NICE is now recommending routine use of ibrutinib in the second-line setting, and has concluded that ibrutinib can be considered for end-of-life situations.

Data from a pooled analysis that were presented at the 2017 ASH Annual Meeting suggest that ibrutinib can extend progression-free survival in this patient population. Overall, 53% of patients treated with ibrutinib were alive at 2 years, 45% were alive at 3 years, and 37% were alive at 5 years. The median OS was 26.7 months.

*******************************

This week, we sat down with Dr Alicia Morgan of Mather Hospital to discuss ongoing research with PARP inhibitors in prostate cancer.

That’s all for today. Thank you for watching OncLive News Network! I’m Gina Columbus.
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Today-

FDA approvals in renal cell carcinoma and chronic myeloma leukemia, priority review designations in non–small cell lung cancer and renal cell carcinoma, and European recommendations for melanoma, mantle cell lymphoma, and a biosimilar.

Welcome to OncLive News Network! I’m Gina Columbus.

The FDA has approved cabozantinib for previously untreated patients with advanced renal cell carcinoma, based on a meaningful improvement in progression-free survival versus sunitinib in the CABOSUN trial. The approval was granted approximately 2 months ahead of an FDA deadline.

In the phase II study, first-line treatment with cabozantinib reduced the risk of progression or death by 52% compared with sunitinib for patients with advanced disease. The median progression-free survival was 8.6 months with cabozantinib versus 5.3 months for sunitinib.

After 30.8 months of follow-up, the median overall survival was 26.6 months in the cabozantinib arm versus 21.2 months in the sunitinib arm, representing a nonstatistically significant 20% reduction in the risk of death.

Cabozantinib showed similar superiority to sunitinib across all prespecified patient subgroups, including risk, bone metastases, and MET status.

*****************************************

In chronic myeloma leukemia, the FDA has approved bosutinib as a first-line treatment for patients with Philadelphia chromosome-positive disease.

The decision was based on data from the open-label phase III BFORE trial, which compared bosutinib with standard of care imatinib.

Results showed that the major molecular response at 12 months was 47.2% with bosutinib versus 36.9% for imatinib. The complete cytogenetic response rate by 12 months was 77.2% with bosutinib compared with 66.4% for patients treated with imatinib.

Additionally, the 6-month MMR was 35.0% with bosutinib and 18.3% with imatinib, and the 9-month MMR was 42.3% for bosutinib and 29.5% for imatinib. The cumulative incidence function of MMR was more favorable with bosutinib, indicating a shorter time to response.

The approval is contingent upon findings from long-term follow up.

*****************************************

The FDA has granted a priority review to a supplemental new drug application for the use of osimertinib as a first-line treatment for patients with non–small cell lung cancer whose tumors harbor EGFR mutations, which include exon 19 deletions or exon 21 substitution mutations.

The application is based on the pivotal phase III FLAURA study, which demonstrated that frontline osimertinib reduced the risk of progression or death by 54% versus standard erlotinib or gefitinib. In the double-blind study, the median progression-free survival was 10.2 months for standard therapy and 18.9 months with osimertinib. The PFS benefit with osimertinib extended across all prespecified subgroups, including patients with CNS metastases.

Moreover, the objective response rate with osimertinib was 80% versus 76% for erlotinib and gefitinib. The median duration of response with osimertinib was 17.2 months versus 8.5 months in the comparator arm.

Under the priority review, the FDA acts within 6 months of receiving a supplemental application, rather than the standard 10 months.

******************************

In renal cell carcinoma, the FDA granted a priority review to a supplemental biologics license application for the combination of nivolumab and ipilimumab as a frontline treatment for intermediate- and poor-risk patients with advanced disease.

The application stems from results of the phase III CheckMate-214 trial, in which frontline treatment with the immunotherapy combination reduced the risk of death by 32% versus sunitinib for patients with metastatic disease.

Findings showed that the median overall survival was not reached with the combination versus 32.9 months with sunitinib. In those specifically with intermediate- and poor-risk RCC, the median OS was not reached in the nivolumab and ipilimumab arm and was 26.0 months in the sunitinib arm, representing a 37% reduction in the risk of death. In those with favorable-risk disease, there was not a benefit for the combination versus sunitinib.

The FDA is scheduled to make its final decision on the sBLA on or before April 16, 2018.

**************************************

The European Union’s Committee for Medicinal Products for Human Use has delivered a positive opinion for Herzuma, a trastuzumab biosimilar, for the treatment of patients with HER2-positive early breast cancer, metastatic breast cancer, or metastatic gastric cancer. The CHMP’s opinion will now go to the European Commission for final review.

A phase III equivalence trial evaluating Herzuma for safety and efficacy compared with trastuzumab showed that rates of pathologic complete response were similar between the treatment arms in the intent-to-treat population at 46.8% for Herzuma and 50.4% for trastuzumab. The estimated difference in pCR proportion between the 2 groups was –.04.

Regarding safety, the percentage of patients reporting treatment-emergent adverse events was 94% in the Herzuma group versus 95% with trastuzumab. Six percent of patients in the Herzuma group experienced grade 3 or higher treatment-emergent adverse events versus 8% in the trastuzumab group.

**************************************

In melanoma, the European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of ipilimumab for the treatment of pediatric patients aged 12 years and older with unresectable or metastatic disease.

According to Bristol-Meyers Squibb, the developer of ipilimumab, the CHMP recommendation is its first positive opinion for an immuno-oncology agent in the pediatric setting.

The application is based on data across 2 trials in which objective responses were observed in 2 of 17 patients aged more than 12 years with advanced melanoma. The responses included 1 partial response that lasted for 16 months.

The pivotal ipilimumab pediatric trials included a dose-finding study involving 33 patients aged 2 to 21 years with relapsed/refractory solid tumors, and a single-arm, open-label trial that accrued 12 patients aged 12 to 16 years with stage III or IV melanoma, either previously treated or untreated.

***********************************

The United Kingdom's National Institute for Health Care and Excellence has published new guidelines recommending ibrutinib as a treatment for patients with relapsed/refractory mantle cell lymphoma.

Ibrutinib is approved for patients who have undergone 1 previous line of therapy, and if Janssen Biotech, the drug’s manufacturer, provides ibrutinib with the discount agreed in the commercial access agreement with NHS England. The amount of the discount was not released.

Earlier this year, NICE said it could not recommend routine use of ibrutinib in MCL because it did not meet NHS requirements for value per QALY. Ibrutinib is currently available through the Cancer Drugs Fund.

NICE is now recommending routine use of ibrutinib in the second-line setting, and has concluded that ibrutinib can be considered for end-of-life situations.

Data from a pooled analysis that were presented at the 2017 ASH Annual Meeting suggest that ibrutinib can extend progression-free survival in this patient population. Overall, 53% of patients treated with ibrutinib were alive at 2 years, 45% were alive at 3 years, and 37% were alive at 5 years. The median OS was 26.7 months.

*******************************

This week, we sat down with Dr Alicia Morgan of Mather Hospital to discuss ongoing research with PARP inhibitors in prostate cancer.

That’s all for today. Thank you for watching OncLive News Network! I’m Gina Columbus.
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