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Lung Cancer. 2018 Nov;125:273-281. doi: 10.1016/j.lungcan.2018.08.019. Epub 2018 Aug 25.

Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non-small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study.

Author information

1
Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA. Electronic address: sgadgeel@med.umich.edu.
2
Taussig Cancer Institute/Cleveland Clinic, Cleveland, OH, USA.
3
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
4
Dana-Farber Cancer Institute, Boston, MA, USA.
5
Fox Chase Cancer Center, Philadelphia, PA, USA.
6
South Texas Accelerated Research Therapeutics, San Antonio, TX, USA.
7
University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
8
University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
9
Nebraska Cancer Specialists, Omaha, NE, USA.
10
National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan.
11
Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, USA.
12
Merck & Co., Inc., Kenilworth, NJ, USA.
13
The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

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.

KEYWORDS:

Antineoplastic agents; Bevacizumab; Carcinoma; Combination; Drug therapy; Non–small-cell lung; Pembrolizumab

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