Pembrolizumab and Platinum-Based Chemotherapy as First-Line Therapy for Advanced Non-Small-Cell Lung Cancer: Phase 1 Cohorts From the KEYNOTE-021 Study
Mené sur 74 patients atteints d'un cancer du poumon non à petites cellules de stade avancé, cet essai de phase I/II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement combinant pembrolizumab et doublet de chimiothérapie à base de sels de platine en traitement de première ligne
Objectives : Platinum-based chemotherapy for advanced non―small-cell lung cancer (NSCLC) has modest benefit overall, but has the potential to amplify immune responses. In cohorts A-C of the multicohort phase 1/2 study KEYNOTE-021 (Clinicaltrials.gov, NCT02039674), we evaluated the combinations of platinum-doublet chemotherapy with the anti―programmed death 1 monocloncal antibody pembrolizumab. Materials and Methods : Patients with previously untreated, advanced NSCLC without EGFR/ALK aberrations were randomized to pembrolizumab 2 or 10 mg/kg Q3W plus carboplatin area under the serum concentration-time curve (AUC) 6 mg/mL/min plus paclitaxel 200 mg/m2 (cohort A, any histology), carboplatin AUC 6 mg/mL/min plus paclitaxel 200 mg/m2 plus bevacizumab 15 mg/kg (cohort B, non-squamous), or carboplatin AUC 5 mg/mL/min plus pemetrexed 500 mg/m2 (cohort C, non-squamous) for 4 cycles followed by maintenance pembrolizumab (cohort A), pembrolizumab plus bevacizumab (cohort B), or pembrolizumab plus pemetrexed (cohort C). Response was assessed by blinded independent central review. Results : Overall, 74 patients were randomized; median follow-up was 21.4, 16.4, and 17.4 months in cohorts A, B, and C, respectively. No dose-limiting toxicities occurred in any cohort at either pembrolizumab dose. Most frequent treatment-related adverse events (AEs) were alopecia, fatigue, and nausea. Treatment-related grade 3/4 AEs occurred in 40%, 42%, and 46% of patients in cohorts A, B, and C, respectively; AEs with possible immune etiology occurred in 24%, 50%, and 38% of patients. Objective response rates were 48%, 56%, and 75% in cohorts A, B, and C. Conclusion : Pembrolizumab in combination with carboplatin-paclitaxel and with pemetrexed-carboplatin yielded encouraging antitumor activity and toxicity consistent with known toxicities of platinum-based chemotherapy or pembrolizumab monotherapy.