Pembrolizumab as First-Line Treatment Significantly Improves Overall Survival in NSCLC Trial

Pembrolizumab (Keytruda) monotherapy as first-line treatment in locally advanced or metastatic non-small cell lung cancer (NSCLC) met its primary endpoint of overall survival (OS) in the Phase 3 KEYNOTE-042 trial, announced Merck in a press release.

An interim analysis by the independent Data Monitoring Committee (DMC) determined that pembrolizumab monotherapy yielded significantly improved OS when compared with platinum-based chemotherapy in patients with a PD-L1 tumor proportion score (TPS) of 1% or higher. The trial sequentially tested OS in patients with a TPS of 50% or higher, a TPS of 20% or higher, and then in the entire study cohort with a TPS of 1% or higher; significantly improved OS was continuously demonstrated for pembrolizumab.

“Improvement in overall survival is the ultimate objective in the treatment of advanced lung cancer,” said Tony Mok, MD, professor in the Department of Clinical Oncology at the Chinese University of Hong Kong. “KEYNOTE-042 is the first randomized Phase 3 study of a single-agent immunotherapy using overall survival as the primary endpoint that has demonstrated significant benefit as first-line therapy in NSCLC patients who tested positive for PD-L1 at 1% or higher.”

The trial will continue to evaluate pembrolizumab’s effect on progression-free survival, the study’s secondary end point, based on the recommendation of DMC. The international, open-label, Phase 3 KEYNOTE-042 study enrolled 1274 patients, randomized 1:1, to receive pembrolizumab or standard of care platinum-based chemotherapy. Patients had no EGFR or ALK genomic tumor aberrations and no previous treatment with systematic therapy for advanced disease.

According to the press release, the demonstrated safety profile of pembrolizumab was consistent with previously reported monotherapy studies involving patients with advanced NSCLC.

“With KEYNOTE-042, Keytruda has now shown a significant survival benefit compared with chemotherapy for patients with locally advanced or metastatic nonsquamous or squamous NSCLC expressing PD-L1 at 1% of higher by tumor proportion score,” said Roger M. Perlmutter, MD, president, Merck Research Laboratories, in a statement. “Keytruda is a foundational treatment for NSCLC and has consistently demonstrated a survival benefit as monotherapy, or in combination with chemotherapy, in the treatment of metastatic lung cancer.”

Pembrolizumab currently has indications for melanoma, head and neck cancer, classical Hodgkin lymphoma, urothelial carcinoma, and gastric cancer. Last month, the FDA accepted a new supplemental Biologics License Application and granted Priority Review for pembrolizumab for the treatment of advanced cervical cancer, marking the 14th regulatory submission accepted by the FDA for the anti-PD-1 therapy.