May 24, 2017 - Episode 1

FDA Approvals in MSI-High Cancers, Priority Reviews in Gastric Cancer and FL, and More


FDA approvals in microsatellite-high instability and mismatch repair-deficient cancers and urothelial carcinoma, priority reviews in gastric cancer and follicular lymphoma, an ODAC recommendation for a drug in breast cancer, and a European recommendation in lung cancer.

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

The FDA has granted an accelerated approval to pembrolizumab for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high or mismatch repair deficient solid tumors that have progressed after prior treatment and who have no satisfactory alternative treatment options. It is also for patients with MSI-H or dMMR colorectal cancer following progression on a fluoropyrimidine, oxaliplatin, and irinotecan.

The approval was based on data from 149 patients with MSI-H or dMMR cancers enrolled across 5 single-arm clinical trials. Ninety patients had CRC and the remaining 59 patients had 1 of 14 other tumor types.

Results showed that the objective response rate with pembrolizumab was 39.6%, including 11 complete responses and 48 partial responses. The ORR was 36% in patients with CRC and 46% in patients with other tumor types, and the median duration of response was not yet reached. Among the patients who responded to pembrolizumab, 78% had responses that lasted for at least 6 months.


Pembrolizumab received another approval from the FDA this past week, this time for patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

The FDA also granted an accelerated approval to frontline pembrolizumab for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.

The approval in the second-line setting was based on the phase III KEYNOTE-045 study, in which single-agent pembrolizumab reduced the risk of death by 27% compared with chemotherapy in patients with advanced urothelial carcinoma whose disease progressed after prior treatment.

The accelerated approval for frontline pembrolizumab in urothelial carcinoma is contingent on the results of a confirmatory trial.


In follicular lymphoma, the FDA granted a priority review designation to copanlisib as a treatment for patients with relapsed/refractory disease who received at 2 least prior therapies.

The new drug application for the PI3K dual-isoform inhibitor is based primarily on findings from the phase II CHRONOS-1 study, which included patients with multiple types of lymphoma.

In the trial, 59% of patients achieved objective responses to copanlisib. The responses were durable, and the median progression-free survival approached 1 year.

Under the priority review program, the FDA will decide on the NDA for copanlisib within 6 months, compared with the standard 10-month review.


A priority review designation was also granted by the FDA to a supplemental biologics license application for pembrolizumab for the treatment of patients with recurrent or advanced gastric or gastroesophageal junction adenocarcinoma. Patients must have undergone at least 2 courses of chemotherapy to receive the treatment.

The application is based on data from cohort 1 of the multicohort, international phase II KEYNOTE-059 trial. Full findings from this study will be presented at the upcoming ASCO Annual Meeting.

At a median follow-up was 5.4 months, the objective response rate was 11.2%. A total of 1.9% of patients had a complete response, 9.3% had a partial response, 17% had stable disease, and 55.6% experienced disease progression.

In PD-L1—positive patients, the ORR was 15.5%, 2% of patients had a complete response, and 13.5% had a partial response.

The agency is expected to announce a decision by September 22, 2017.


The FDA’s Oncologic Drugs Advisory Committee voted 12-4 recommending approval of neratinib for the extended adjuvant treatment of patients with early stage, HER2-positive breast cancer following postoperative trastuzumab.

ODAC based its recommendation on findings 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 findings showed 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, compared with 7% in HR-negative patients.

Diarrhea was the primary safety concern with neratinib considered by the panel, as 95% of patients in the ExteNET trial who received the tyrosine kinase inhibitor experienced the adverse event, including 40% of patients who experienced it as a grade 3 event. Moreover, diarrhea led to study discontinuation for 16.8% of patients.

Results from the ongoing phase II CONTROL trial suggest that antidiarrheal prophylaxis can control the occurrence and severity of diarrhea among patients receiving neratinib.

ODAC also stressed concerns over the numerous amendments to the ExteNet study protocol, the effects of which included enriching the study population with high-risk patients, reducing the trial follow-up interval from 5 years to 2 years, and implementing a reconsent process to increase follow-up to 5 years after randomization. Despite these amendments, data from sensitivity analyses were enough to assure the panel that neratinib had a positive effect in this patient population.

The FDA will now make its final decision on neratinib. The agency is not required to follow the ODAC recommendation.


Finally, the EMA’s Committee for Medicinal Products for Human Use has recommended approval of ceritinib for the first-line treatment of patients with ALK-positive, metastatic non—small cell lung cancer.

The priority review is based on findings from the phase III ASCEND-4 trial, in which ceritinib reduced the risk of disease progression or death by 45% compared with standard chemotherapy. The median progression-free survival benefit favoring ceritinib was 8.5 months.

The positive opinion will now be reviewed by the European Commission and a final approval decision for use in the European Union is expected in about 2 months.

Ceritinib is approved in the EU for the treatment of patients with ALK-positive advanced NSCLC previously treated with crizotinib. In the United States, ceritinib was approved by the FDA in April 2014 for use in the same second-line setting. The FDA granted a priority review to ceritinib in February 2017 as a first-line treatment for patients with ALK-positive, metastatic NSCLC.


This week, Dr. Julian Sanchez of Moffitt Cancer Center discussed research findings in colon cancer reported on a presscast held ahead of the 2017 ASCO Annual Meeting.

That’s all for today.

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