Outcomes With Pembrolizumab Plus Platinum-Based Chemotherapy for Patients With NSCLC and Stable Brain Metastases: Pooled Analysis of KEYNOTE-021, -189, and -407

• DOI: 10.1016/j.jtho.2021.06.020
• Publication Date: 2021-07-12T15:25:59Z
• Authors: Steven F. Powell; Delvys Rodríguez-...; Corey J. Langer; Ali Tafreshi; Luis Paz-Ares; Hans-Georg Kopp; Jeronimo Rodrígue...; Dariusz M. Kowalski; Ying Cheng; Takayasu Kurata; Mark M. Awad; Jinaxin Lin; Bin Zhao; M. Catherine Piet...; Bilal Piperdi; Marina C. Garassino
• Keywords: Pooled analysis

IntroductionThis exploratory analysis retrospectively evaluated outcomes in patients with advanced NSCLC to determine whether baseline brain metastases influenced the efficacy of first-line pembrolizumab plus chemotherapy versus alone.MethodsWe pooled data for KEYNOTE-021 cohort G (nonsquamous), KEYNOTE-189 and KEYNOTE-407 (squamous). Patients were assigned platinum-doublet or without addition 35 cycles 200 mg every 3 weeks. All studies permitted enrollment previously treated untreated (KEYNOTE-189 only) stable metastases. clinically 2 more weeks (≥4 wk G), had no evidence new enlarging metastases, steroid use at least days before dosing. known asymptomatic required regular imaging brain.ResultsA total 1298 included, 171 1127 Median (range) durations follow-up cutoff 10.9 (0.1‒35.1) 11.0 (0.1‒34.9) months, respectively. Hazard ratios (pembrolizumab + chemotherapy/chemotherapy) similar overall survival (0.48 [95% confidence interval (CI): 0.32‒0.70] 0.63 CI: 0.53‒0.75], respectively) progression-free (0.44 0.31‒0.62] 0.55 0.48‒0.63], respectively). In median was 18.8 months 7.6 chemotherapy, 6.9 4.1 Objective response rates higher duration longer regardless metastasis status. Incidences treatment-related adverse events 88.2% 82.8% among 94.5% 90.6% those without.ConclusionsWith metastasis, platinum-based histology-specific improved clinical alone across all programmed death ligand 1 subgroups, including tumor proportion score less than 1% a manageable safety profile NSCLC. This regimen is standard-of-care treatment option treatment-naive NSCLC,