Five Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel for Previously Treated, Programmed Death-Ligand 1–Positive Advanced NSCLC

Roy S. Herbst, Edward B. Garon, Dong Wan Kim, Byoung Chul Cho, Radj Gervais, Jose L. Perez-Gracia, Ji Youn Han, Margarita Majem, Martin D. Forster, Isabelle Monnet, Silvia Novello, Matthew A. Gubens, Michael Boyer, Wu Chou Su, Ayman Samkari, Erin H. Jensen, Julie Kobie, Bilal Piperdi, Paul Baas

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Introduction: In the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in patients with previously treated, advanced NSCLC with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) ≥50% and ≥1%. We report 5-year efficacy and safety follow-up for the KEYNOTE-010 study. Methods: Patients were randomized to pembrolizumab 2 mg/kg or 10 mg/kg once every 3 weeks or docetaxel 75 mg/m2 once every 3 weeks for up to 35 cycles (2 y). Patients who completed pembrolizumab treatment and subsequently had recurrence could receive second-course pembrolizumab for up to 17 cycles (1 y). Pembrolizumab doses were pooled in this analysis. Results: A total of 1034 patients were randomized (pembrolizumab, n = 691; docetaxel, n = 343). Median study follow-up was 67.4 months (range: 60.0‒77.9). The hazard ratio (95% confidence interval) for OS was 0.55 (0.44‒0.69) for patients with PD-L1 TPS ≥50% and 0.70 (0.61‒0.80) with PD-L1 TPS ≥1%. The 5-year OS rates for pembrolizumab versus docetaxel were 25.0% versus 8.2% in patients with PD-L1 TPS ≥50% and 15.6% versus 6.5% with PD-L1 TPS ≥1%. Among 79 patients who completed 35 cycles/2 years of pembrolizumab, the OS rate 3 years after completion (∼5 y from randomization) was 83.0%. A total of 21 patients received second-course pembrolizumab; 11 (52.4%) had an objective response after starting the second course and 15 (71.4%) were alive at data cutoff. Exploratory biomarker analysis revealed that higher tissue tumor mutational burden (≥175 mutations per exome) was associated with improved outcomes with pembrolizumab. Conclusions: Pembrolizumab continued to provide long-term benefit than docetaxel in patients with previously treated advanced NSCLC with PD-L1 TPS ≥50% and ≥1%. Our findings confirm pembrolizumab as a standard-of-care treatment in the second-line or later setting.

Original languageEnglish (US)
Pages (from-to)1718-1732
Number of pages15
JournalJournal of Thoracic Oncology
Volume16
Issue number10
DOIs
StatePublished - Oct 2021
Externally publishedYes

Keywords

  • Chemotherapy
  • Non‒small-cell lung cancer
  • PD-L1
  • Pembrolizumab

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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