FDA Approves Pembrolizumab/Chemotherapy Combination for Metastatic Nonsquamous NSCLC

The US Food and Drug Administration (FDA) has approved Merck & Co.’s pembrolizumab (KEYTRUDA) in combination with pemetrexed and platinum as first-line treatment for patients with metastatic, non-squamous non-small cell lung cancer (NSqNSCLC), with no EGFR or ALK genomic tumor aberrations.

Results from the randomized, multicenter, double-blind, active controlled KEYNOTE-189 trial served as the basis for the approval. The study enrolled 616 patients who were administered first-line treatment for metastatic NSqNSCLC. Patients were randomized (2:1) to receive pembrolizumab (or placebo) in combination with pemetrexed, and investigator’s choice of either cisplatin or carboplatin every 3 weeks for 4 cycles followed by pembrolizumab (or placebo) and pemetrexed. Until disease progression, unacceptable toxicity, or a maximum of 24 months, treatment with pembrolizumab continued.

Overall survival (OS) and progression-free survival (PFS), as assessed by a blinded independent committee review (RECIST 1.1.), served as the primary efficacy outcome measures for the trial.

A statistically significant improvement in OS for patients randomized to receive pembrolizumab and chemotherapy (HR 0.49; 95% CI: 0.38, 0.64; p<0.00001) in a pre-specified interim analysis was demonstrated in the trial. At the time of the data cut-off, the median OS was not reached in the pembrolizumab plus chemotherapy arm, while the OS was 11.3 months for those in the chemotherapy arm.

However, an improvement in progression-free survival (PFS) for patients randomized to receive pembrolizumab plus chemotherapy (HR 0.52; 95% CI: 0.43, 0.64; p<0.00001) was demonstrated in the trial. For patients receiving pembrolizumab plus chemotherapy, the median PFS was 8.8 months, while for those who received chemotherapy alone had a median PFS of 4.9 months. For those in the pembrolizumab plus chemotherapy arm, the overall response rate was significantly higher (48% vs. 19%; p=0.0001) compared with the chemotherapy arm, and the median response duration was 11.2 months and 7.8 months, respectively.

In ≥20% of patients in KEYNOTE-189, the most common adverse reactions reported were fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, and pyrexia.

The FDA recommends a 200 mg dose of pembrolizumab to be delivered via intravenous infusion over 30 minutes every 3 weeks.

Previously, pembrolizumab (KEYTRUDA) was approved by the FDA for the treatment of patients with refractory primary mediastinal large B-cell lymphoma (PMBCL) who have relapsed after 2 or more previous lines of therapy. The drug was also granted a new supplemental Biologics License Application (sBLA) for the treatment of advanced hepatocellular carcinoma (HCC). Pembrolizumab has also been found to exhibit high response rates in patients with relapsed/refractory (r/r) Hodgkin lymphoma when used in combination with AFM13.