Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non–small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study
Journal
Lung Cancer
Journal Volume
125
Pages
273-281
Date Issued
2018
Author(s)
Gadgeel S.M
Stevenson J.P
Langer C.J
Gandhi L
Borghaei H
Patnaik A
Villaruz L.C
Gubens M
Hauke R
Sequist L.V
Bachman R
Saraf S
Raftopoulos H
Papadimitrakopoulou V.
Abstract
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. ? 2018 Elsevier B.V.
SDGs
Other Subjects
alanine aminotransferase; aspartate aminotransferase; bevacizumab; carboplatin; paclitaxel; pembrolizumab; pemetrexed; antineoplastic agent; bevacizumab; carboplatin; monoclonal antibody; paclitaxel; pembrolizumab; pemetrexed; platinum complex; adrenal insufficiency; adult; advanced cancer; aged; alanine aminotransferase blood level; alopecia; anemia; antineoplastic activity; arthralgia; Article; aspartate aminotransferase blood level; cancer combination chemotherapy; clinical effectiveness; cohort analysis; colitis; constipation; controlled study; decreased appetite; diarrhea; drug blood level; drug eruption; drug safety; dry skin; dysgeusia; epistaxis; fatigue; female; follow up; human; hyperthyroidism; hypothyroidism; infusion related reaction; leukocyte count; maculopapular rash; maintenance therapy; major clinical study; male; multiple cycle treatment; nausea; neutrophil count; non small cell lung cancer; pain; pancreatitis; peripheral edema; peripheral neuropathy; phase 1 clinical trial; pneumonia; primary health care; priority journal; pruritus; randomized controlled trial; rash; response evaluation criteria in solid tumors; sensory neuropathy; side effect; skin manifestation; stomatitis; thrombocytopenia; thyroiditis; treatment outcome; treatment response; uveitis; lung tumor; middle aged; non small cell lung cancer; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carboplatin; Carcinoma, Non-Small-Cell Lung; Cohort Studies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Paclitaxel; Pemetrexed
Publisher
Elsevier Ireland Ltd
Type
journal article