FDA Grants Priority Review to Frontline Keytruda Combination in Metastatic NSCLC

The Food and Drug Administration (FDA) granted a priority review to Keytruda (pembrolizumab) in combination with chemotherapy as a first-line treatment for metastatic squamous non-small cell lung cancer (NSCLC), regardless of PD-L1 expression, according to Merck, the manufacturer of the anti-PD-1 agent.

The agency is set to make its decision by Oct. 30, 2018.

“Keytruda has already been established as an important treatment option for non-small cell lung cancer in the first-line setting, and with our broad development program in lung cancer, we are committed to improving survival for as many patients as we can,” Roy Baynes, M.D., Ph.D., senior vice president and head of global clinical development, and chief medical officer of Merck Research Laboratories, said in a company-issued release.

“We are pleased that our application for squamous cell carcinoma — a historically challenging-to-treat disease – is under priority review with the FDA,” he added.

The supplemental Biologics License Application is based on data from the phase 3 KEYNOTE-407 trial, designed to evaluate frontline Keytruda plus Abraxane (carboplatin/paclitaxel or nab-paclitaxel) compared with chemotherapy alone in 559 patients with metastatic squamous NSCLC.

Results from the trial were recently presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting.

Patients in the treatment arm received 200 mg/m2 of carboplatin (AUC 6) and paclitaxel every three weeks or 100 mg/m2 of weekly nab-paclitaxel, plus 200 mg of Keytruda every three weeks. The control arm received chemotherapy for four cycles, each three weeks.

After the initial four cycles, patients randomized to the placebo arm were allowed to cross over to receive Keytruda for the potential additional 31 cycles. Both arms followed treatment with either single-agent Keytruda (200 mg every three weeks) or placebo for up to 31 cycles, for a potential total of 35 cycles.

The median overall survival (OS) was 15.9 months with Keytruda compared with 11.3 months with chemotherapy alone. Of note, the OS benefit was observed regardless of PD-L1 expression level, choice of taxane, age, sex, and ECOG performance status.

Progression-free survival (PFS) was also improved with the addition of Keytruda, with a median PFS of 6.4 months in the treatment arm compared with 4.8 months in those who received chemotherapy alone. While the PFS benefit was also observed across all PD-L1 expression levels, there was a correlation between an increase in PD-L1 level and a greater magnitude of benefit.

The objective response rate (ORR) in the Keytruda arm was 57.9 percent, comprising a complete response (CR) rate of 1.4 percent and a partial response (PR) rate of 56.5 percent. In the control arm, the ORR was 38.4 percent, including a CR rate of 2.1 percent and a PR rate of 36.3 percent. The duration of response was 7.7 months compared with 4.8 months, respectively.

Overall, 28.1 percent of the Keytruda arm experienced stable disease, 6.1 percent had progressive disease and 2.2 percent of patients were not evaluable for response compared with 37 percent, 13.9 percent and 2.5 percent, respectively, in the control arm.

Grade 3/5 all-cause side occurred in 69.8 percent of patients in the Keytruda arm compared with 68.2 percent in the placebo arm. Grade 3/5 immune-mediated side effects and infusion reactions occurred in 10.8 percent and 3.2 percent, respectively. More patients discontinued therapy due to treatment-related side effects in the Keytruda arm (23.4 percent vs. 11.8 percent). Treatment-related side effects led to death in 3.6 percent compared with 2.1 percent in the treatment arm compared with placebo.