Pembrolizumab Monotherapy in NSCLC Meets Primary Endpoint in Phase III KEYNOTE-042 Study

On April 9, the phase III KEYNOTE-042 trial evaluating pembrolizumab (Keytruda) as monotherapy for the first-line treatment of locally advanced or metastatic non–small cell lung cancer (NSCLC, including nonsquamous or squamous histologies) met its primary endpoint of overall survival (OS). An interim analysis conducted by the independent Data Monitoring Committee (DMC) demonstrated that treatment with pembrolizumab resulted in significantly longer OS than platinum-based chemotherapy (carboplatin plus paclitaxel or carboplatin plus pemetrexed [Alimta]) in patients with a programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) of ≥ 1%. As part of a prespecified analysis plan, OS was sequentially tested and was significantly improved in patients with a TPS of ≥ 50%, with a TPS of ≥ 20% and then in the entire study population with a TPS of ≥ 1%. The safety profile of pembrolizumab in this trial was consistent with that observed in previously reported monotherapy studies involving patients with advanced NSCLC.

Based on the recommendation of the DMC, the trial will continue to evaluate progression-free survival (PFS), which is a secondary endpoint. Results from KEYNOTE-042 will be presented at an upcoming medical meeting and submitted to regulatory authorities worldwide.

“With KEYNOTE-042, pembrolizumab 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% or higher by tumor proportion score,” said Roger M. Perlmutter, MD, PhD, President, Merck Research Laboratories. “Pembrolizumab 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. We sincerely thank the patients and clinical investigators for their participation in this important study.”

“Improvement in overall survival is the ultimate objective in the treatment of advanced lung cancer. KEYNOTE-042 is the first randomized phase III 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,” said Tony Mok, BMSc, MD, FRCP(C), FRCP(Edin), FHKCP, FHKAM(Medicine), FASCO, Professor in the Department of Clinical Oncology at the Chinese University of Hong Kong.

More About KEYNOTE-042

KEYNOTE-042 is an international, randomized, open-label phase III study investigating pembrolizumab monotherapy compared to standard of care platinum-based chemotherapy in patients with locally advanced or metastatic PD-L1 positive (TPS ≥ 1%) NSCLC. Patients had no EGFR or ALK genomic tumor aberrations and had not previously received systemic therapy for advanced disease. The study enrolled 1,274 patients randomized 1:1 to receive either pembrolizumab (200 mg fixed dose every 3 weeks) as monotherapy or investigator's choice of platinum-based chemotherapy as follows:

  • Carboplatin AUC 5 or 6 mg/mL/min plus paclitaxel 200 mg/m2 every 3 weeks for a maximum of six cycles for patients with squamous NSCLC; or
  • Carboplatin AUC 5 or 6 mg/mL/min plus pemetrexed 500 mg/m2 every 3 weeks for a maximum of six cycles, followed by optional pemetrexed 500 mg/m2 for patients with nonsquamous NSCLC.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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