PMID- 30429032
OWN - NLM
STAT- MEDLINE
DCOM- 20190830
LR  - 20191204
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Print)
IS  - 0169-5002 (Linking)
VI  - 125
DP  - 2018 Nov
TI  - Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced 
      non-small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study.
PG  - 273-281
LID - S0169-5002(18)30536-1 [pii]
LID - 10.1016/j.lungcan.2018.08.019 [doi]
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/m(2) (cohort A, any histology), carboplatin AUC 6 mg/mL/min 
      plus paclitaxel 200 mg/m(2) plus bevacizumab 15 mg/kg (cohort B, non-squamous), 
      or carboplatin AUC 5 mg/mL/min plus pemetrexed 500 mg/m(2) (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.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Gadgeel, Shirish M
AU  - Gadgeel SM
AD  - Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA. Electronic 
      address: sgadgeel@med.umich.edu.
FAU - Stevenson, James P
AU  - Stevenson JP
AD  - Taussig Cancer Institute/Cleveland Clinic, Cleveland, OH, USA.
FAU - Langer, Corey J
AU  - Langer CJ
AD  - Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
FAU - Gandhi, Leena
AU  - Gandhi L
AD  - Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Borghaei, Hossein
AU  - Borghaei H
AD  - Fox Chase Cancer Center, Philadelphia, PA, USA.
FAU - Patnaik, Amita
AU  - Patnaik A
AD  - South Texas Accelerated Research Therapeutics, San Antonio, TX, USA.
FAU - Villaruz, Liza C
AU  - Villaruz LC
AD  - University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
FAU - Gubens, Matthew
AU  - Gubens M
AD  - University of California, San Francisco, Helen Diller Family Comprehensive Cancer 
      Center, San Francisco, CA, USA.
FAU - Hauke, Ralph
AU  - Hauke R
AD  - Nebraska Cancer Specialists, Omaha, NE, USA.
FAU - Yang, James Chih-Hsin
AU  - Yang JC
AD  - National Taiwan University Hospital and National Taiwan University Cancer Center, 
      Taipei, Taiwan.
FAU - Sequist, Lecia V
AU  - Sequist LV
AD  - Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, 
      MA, USA.
FAU - Bachman, Robert
AU  - Bachman R
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Saraf, Sanatan
AU  - Saraf S
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Raftopoulos, Harry
AU  - Raftopoulos H
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Papadimitrakopoulou, Vassiliki
AU  - Papadimitrakopoulou V
AD  - The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02039674
GR  - P30 CA022453/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180825
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Organoplatinum Compounds)
RN  - 04Q9AIZ7NO (Pemetrexed)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - BG3F62OND5 (Carboplatin)
RN  - DPT0O3T46P (pembrolizumab)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Bevacizumab/administration & dosage
MH  - Carboplatin/administration & dosage
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy
MH  - Cohort Studies
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Organoplatinum Compounds/administration & dosage
MH  - Paclitaxel/administration & dosage
MH  - Pemetrexed/administration & dosage
PMC - PMC6886233
MID - NIHMS1060337
OTO - NOTNLM
OT  - Antineoplastic agents
OT  - Bevacizumab
OT  - Carcinoma
OT  - Combination
OT  - Drug therapy
OT  - Non-small-cell lung
OT  - Pembrolizumab
COIS- Author conflict of interest Gadgeel: Honoraria from Genentech-Roche and 
      AstraZeneca; consulting for Pfizer, AstraZeneca, Genentech-Roche, ARIAD, 
      Bristol-Myers Squibb, and Novartis. Stevenson: Research funding from Merck, 
      Bayer, and Bristol-Myers Squibb. Langer: Grants from Merck, Clovis, GSK, 
      Genentech-Roche, Advantagene, and Inovio; personal fees from Lilly, AZ, Clovis, 
      Bristol-Myers Squibb, Genentech-Roche, Synta, Abbvie, and Amgen. Gandhi: Advisory 
      boards for Genentech/Roche, Merck, AstraZeneca and Ignyta; paid consulting for 
      Celldex and Eli Lilly; research funding from Bristol-Myers Squibb IION Foundation 
      and Merck; current employee of Eli Lilly and Company as of June 25, 2018. 
      Borghaei: Advisory boards for Bristol-Myers Squibb, Lilly, Celgene, Genenetch, 
      Novartis, Astra Zeneca, Trovagene, Merck, EMD-Serono, and Pfizer; research 
      funding from Celgene, Merck, and Millennium; honoraria from Celgene; travel 
      expenses from all companies listed here. Patnaik: Research funding from Merck to 
      institution. Villaruz: None declared. Gubens: Advisory boards for AbbVie, ARIAD, 
      AstraZeneca, Bristol-Myers Squibb, Genentech/Roche, Mersana, and Novartis; 
      research funding from Celegne, Merck, Novartis, OncoMed, and Roche. Hauke: 
      Honoraria from Best Doctors, Inc; research funding by US Oncology, Bristol-Myers 
      Squibb, Merck, Amgen, SOTIO, and Pharmacyclics; stock ownership for Aethlon; 
      patent pending on an immunotherapeutic. Yang: Personal fees from Boehringer 
      Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai, Astellas, MSD, Merck Serono, 
      Pfizer, Novartis, Clovis Oncology, Celgene, Merrimack, Yuhan Pharmaceutical, 
      Bristol-Myers Squibb, Ono Pharmaceutical, and AstraZeneca. Sequist: Advisory 
      boards for AstraZeneca, Bristol-Myers Squibb, ARIAD, and Genentech; research 
      funding from Clovis, Novartis, Boehringer Ingelheim, Merrimack, Merck, and 
      AstraZeneca. Bachman: employee of Merck Sharp & Dohme, Corp., a subsidiary of 
      Merck & Co., Inc., Kenilworth, NJ, USA. Saraf: employee of Merck Sharp & Dohme, 
      Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Raftopoulos: 
      employee of Merck Sharp & Dohme, Corp., a subsidiary of Merck & Co., Inc., 
      Kenilworth, NJ, USA. Papadimitrakopoulou: Advisory boards for Bristol-Myers 
      Squibb, AstraZeneca, Celgene, Janssen, Merck, OncLive, Genentech, Merck & Co, 
      Araxes Pharma, LLC, Nektar Therapeutics, Takeda Pharmaceuticals, and Eli Lilly & 
      Co.; speakers' bureau for Creative Educational Concepts (CEC Oncology); research 
      funding from Merck & Co., NIH/NCI, Bristol-Myers Squibb, Oregon Health Science 
      University, Cancer Prevention & Research Institute of Texas (CPRIT), and American 
      Association for Cancer Research (AACR).
EDAT- 2018/11/16 06:00
MHDA- 2019/08/31 06:00
PMCR- 2019/12/02
CRDT- 2018/11/16 06:00
PHST- 2018/06/15 00:00 [received]
PHST- 2018/08/16 00:00 [revised]
PHST- 2018/08/23 00:00 [accepted]
PHST- 2018/11/16 06:00 [entrez]
PHST- 2018/11/16 06:00 [pubmed]
PHST- 2019/08/31 06:00 [medline]
PHST- 2019/12/02 00:00 [pmc-release]
AID - S0169-5002(18)30536-1 [pii]
AID - 10.1016/j.lungcan.2018.08.019 [doi]
PST - ppublish
SO  - Lung Cancer. 2018 Nov;125:273-281. doi: 10.1016/j.lungcan.2018.08.019. Epub 2018 
      Aug 25.