TY - JOUR
T1 - Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non–small-cell lung cancer
T2 - Phase 1 cohorts from the KEYNOTE-021 study
AU - Gadgeel, Shirish M.
AU - Stevenson, James P.
AU - Langer, Corey J.
AU - Gandhi, Leena
AU - Borghaei, Hossein
AU - Patnaik, Amita
AU - Villaruz, Liza C.
AU - Gubens, Matthew
AU - Hauke, Ralph
AU - Yang, James Chih Hsin
AU - Sequist, Lecia V.
AU - Bachman, Robert
AU - Saraf, Sanatan
AU - Raftopoulos, Harry
AU - Papadimitrakopoulou, Vassiliki
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/11
Y1 - 2018/11
N2 - 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 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, respectively. Objective response rates were 48%, 56%, and 75% in cohorts A, B, and C, respectively. 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.
AB - 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 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, respectively. Objective response rates were 48%, 56%, and 75% in cohorts A, B, and C, respectively. 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.
KW - Adult
KW - Aged
KW - Antibodies, Monoclonal, Humanized/administration & dosage
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Bevacizumab/administration & dosage
KW - Carboplatin/administration & dosage
KW - Carcinoma, Non-Small-Cell Lung/drug therapy
KW - Cohort Studies
KW - Female
KW - Humans
KW - Lung Neoplasms/drug therapy
KW - Male
KW - Middle Aged
KW - Organoplatinum Compounds/administration & dosage
KW - Paclitaxel/administration & dosage
KW - Pemetrexed/administration & dosage
UR - https://www.scopus.com/pages/publications/85054844104
U2 - 10.1016/j.lungcan.2018.08.019
DO - 10.1016/j.lungcan.2018.08.019
M3 - Article
C2 - 30429032
AN - SCOPUS:85054844104
SN - 0169-5002
VL - 125
SP - 273
EP - 281
JO - Lung Cancer
JF - Lung Cancer
ER -
