July 26, 2017 : Episode 1

FDA Approvals in Breast Cancer and Melanoma, Disappointing Results in HNSCC, and More



FDA approvals in breast cancer and pediatric melanoma, disappointing results in a head and neck cancer trial, and European approval recommendations in follicular lymphoma, non—small cell lung cancer, and urothelial carcinoma.

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

The FDA has approved neratinib for the extended adjuvant treatment of patients with early stage, HER2-positive breast cancer following postoperative trastuzumab.

The decision was based on data from the phase III ExteNET trial and the phase II CONTROL trial. In the primary analysis of the ExteNET trial, the invasive disease-free survival rate at 2 years was 94.2% with neratinib versus 91.9% with placebo.

The results indicated that the benefit may vary based on hormone receptor status. An exploratory subgroup analysis indicated that neratinib lowered the risk of recurrence by 51% in HR-positive patients versus 7% in HR-negative patients.

Additionally, the approval follows a 12-4 recommendation from the FDA’s Oncologic Drugs Advisory Committee.

Diarrhea was the primary safety concern associated with neratinib, as 95% of patients in the ExteNET trial who received the drug experienced it, including grade 3 diarrhea in 40% of patients. However, results from the ongoing phase II CONTROL trial suggest that antidiarrheal prophylaxis can control the occurrence and severity of diarrhea among patients receiving neratinib.


In melanoma, the FDA has approved ipilimumab for the treatment of patients aged 12 and older with unresectable or metastatic disease.

The expanded indication for ipilimumab is based on data across 2 clinical trials in which objective responses were observed in 2 of 17 patients 12 years or older with advanced melanoma. The responses included 1 partial response that lasted for 16 months.

The approved ipilimumab dose for pediatric patients with melanoma is 3 mg/kg administered intravenously over 90 minutes every 3 weeks for 4 doses.

According to BMS, the manufacturer of the CTLA-4 inhibitor, the safety profile of ipilimumab in children and adolescent patients was comparable to the safety profile in adult patients.


In the phase III KEYNOTE-040 trial, pembrolizumab did not meet its primary endpoint of overall survival in patients with previously treated recurrent or metastatic head and neck squamous cell carcinoma.

The study evaluated pembrolizumab versus standard chemotherapy with methotrexate, docetaxel or cetuximab, and results showed that the hazard ratio for OS with pembrolizumab was 0.82. Full data will be presented at an upcoming medical meeting.

Pembrolizumab was granted an accelerated approval by the FDA in August 2016 for patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy based on results from the phase Ib KEYNOTE-012 trial. A full approval was contingent on results from confirmatory studies, such as KEYNOTE-040.

Merck, the manufacturer of pembrolizumab, did not say what significance, if any, these results might have for KEYNOTE-048, which is the phase III trial comparing pembrolizumab with platinum-based chemotherapy plus 5-FU and cetuximab, or in combination with platinum-based therapy and 5-FU as a frontline treatment for patients with recurrent or metastatic HNSCC.


The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended the frontline approval of obinutuzumab for the treatment of patients with follicular lymphoma.

The positive opinion is specifically for the use of obinutuzumab in combination with chemotherapy, followed by obinutuzumab maintenance in patients who achieve a response.

The recommendation is based on findings from the phase III GALLIUM study, in which combining obinutuzumab with chemotherapy in the first-line setting reduced the risk of disease progression or death by 34% versus rituximab plus chemotherapy in patients with follicular lymphoma.

Obinutuzumab is currently approved in the United States and EU for use in combination with bendamustine for patients with certain types of previously treated follicular lymphoma.


The European Medicines Agency’s Committee for Medicinal Products for Human Use also took a positive position on indications for atezolizumab in both non—small cell lung cancer and urothelial carcinoma.

The CHMP supports atezolizumab monotherapy for adults with previously-treated, locally advanced or metastatic NSCLC, and for adults with locally advanced or metastatic urothelial carcinoma who have been previously treated with a platinum-based chemotherapy or who are ineligible for cisplatin chemotherapy.

The opinion was based on results in NSCLC from the phase III OAK and the phase II POPLAR studies, and results from the phase III IMvigor211 and cohorts 1 and 2 from the single-arm phase II IMvigor210 studies in urothelial carcinoma.

The European Commission will now make a final approval decision on use of atezolizumab in the European Union for these indications.


This week, we sat down with Dr. Ezra Cohen of the University of California San Diego to discuss NK-directed therapy in head and neck cancer.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.

Related Content