A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407

Luis Paz-Ares, David Vicente, Ali Tafreshi, Andrew Robinson, Hector Soto Parra, Julien Mazières, Barbara Hermes, Irfan Cicin, Balazs Medgyasszay, Jerónimo Rodríguez-Cid, Isamu Okamoto, Sung Sook Lee, Rodryg Ramlau, Vladimir Vladimirov, Ying Cheng, Xuan Deng, Ying Zhang, Tuba Bas, Bilal Piperdi, Balazs Halmos

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Abstract

Introduction: In the randomized KEYNOTE-407 study (ClinicalTrials.gov, NCT02775435), pembrolizumab plus carboplatin and paclitaxel/nab-paclitaxel (chemotherapy) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus chemotherapy in patients with previously untreated metastatic squamous NSCLC. We report updated efficacy outcomes from the protocol-specified final analysis and, for the first time, progression on next line of treatment. Methods: Eligible patients were randomized to chemotherapy plus either pembrolizumab (n = 278) or placebo (n = 281). After positive results from the second interim analysis, patients still receiving placebo could cross over to pembrolizumab monotherapy at the time of confirmed progressive disease. The primary end points were OS and PFS. PFS-2 (time from randomization to progression on next-line treatment/death, whichever occurred first) was an exploratory end point. Results: After median (range) follow-up of 14.3 (0.1–31.3) months, pembrolizumab plus chemotherapy continued to exhibit a clinically meaningful improvement over placebo plus chemotherapy in OS (median, 17.1 mo [95% confidence interval (CI): 14.4‒19.9] versus 11.6 mo [95% CI: 10.1‒13.7]; hazard ratio [HR], 0.71 [95% CI: 0.58‒0.88]) and PFS (median, 8.0 mo [95% CI: 6.3‒8.4] versus 5.1 mo [95% CI: 4.3‒6.0]; HR, 0.57 [95% CI: 0.47‒0.69]). PFS-2 was longer for patients randomized to first-line pembrolizumab plus chemotherapy (HR, 0.59 [95% CI: 0.49‒0.72]). Grade 3 to 5 adverse events occurred in 74.1% and 69.6% of patients receiving pembrolizumab plus chemotherapy and placebo plus chemotherapy, respectively. Conclusions: Pembrolizumab plus chemotherapy continued to exhibit substantially improved OS and PFS in patients with metastatic squamous NSCLC. The PFS-2 outcomes support pembrolizumab plus chemotherapy as a standard first-line treatment in patients with metastatic squamous NSCLC.

Original languageEnglish
JournalJournal of Thoracic Oncology
DOIs
Publication statusAccepted/In press - 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

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    Paz-Ares, L., Vicente, D., Tafreshi, A., Robinson, A., Soto Parra, H., Mazières, J., Hermes, B., Cicin, I., Medgyasszay, B., Rodríguez-Cid, J., Okamoto, I., Lee, S. S., Ramlau, R., Vladimirov, V., Cheng, Y., Deng, X., Zhang, Y., Bas, T., Piperdi, B., & Halmos, B. (Accepted/In press). A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. Journal of Thoracic Oncology. https://doi.org/10.1016/j.jtho.2020.06.015