PMID- 33730652
OWN - NLM
STAT- MEDLINE
DCOM- 20210621
LR  - 20230717
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 155
DP  - 2021 May
TI  - Safety of pemetrexed plus platinum in combination with pembrolizumab for 
      metastatic nonsquamous non-small cell lung cancer: A post hoc analysis of 
      KEYNOTE-189.
PG  - 53-60
LID - S0169-5002(21)00081-7 [pii]
LID - 10.1016/j.lungcan.2021.02.021 [doi]
AB  - OBJECTIVES: This post hoc analysis assessed the safety of pemetrexed and platinum 
      in combination with pembrolizumab, including time-to-onset and time-to-resolution 
      of all-cause any-grade and grade >/=3 adverse events (AEs) and renal AEs. MATERIALS 
      AND METHODS: Patient-level data from KEYNOTE-189 were analyzed in the 
      all-subjects-as-treated population (pembrolizumab arm, n = 405; placebo arm, 
      n = 202), and among patients who received >/=5 cycles of pemetrexed 
      (pemetrexed/pembrolizumab/platinum arm, n = 310; pemetrexed/placebo/platinum arm, 
      n = 135). All-cause AEs were selected based on >/=2 % incidence from previously 
      reported KEYNOTE-189 data and included neutropenia, febrile neutropenia, anemia, 
      thrombocytopenia, asthenia, fatigue, dyspnea, diarrhea, nausea, vomiting, 
      pneumonitis, and renal events. Descriptive statistics summarized all-cause AEs. 
      Medians and interquartile ranges were used to examine time-to-onset and 
      time-to-resolution. The data cutoff was November 8, 2017. RESULTS: In both 
      treatment arms, most non-hematologic (nausea, vomiting, diarrhea, and asthenia), 
      and hematologic (febrile neutropenia, thrombocytopenia, and neutropenia) grade >/=3 
      AEs with >/=2 % incidence had a median time-to-onset within the first 4 cycles, and 
      a median time-to-resolution of within 2 weeks from onset. A small number of AEs 
      had longer median time-to-onset (pneumonitis and fatigue) and median 
      time-to-resolution (pneumonitis, fatigue, acute kidney injury, and anemia). Among 
      patients who received >/=5 cycles of pemetrexed, the incidence of any-grade renal 
      toxicity in the pemetrexed/pembrolizumab/platinum arm was 2.3 % in Cycles 1-4, 
      4.8 % in Cycles 5-8, 2.6 % in Cycles 9-12, and 2.5 % in Cycles >/=13; and, in the 
      pemetrexed/placebo/platinum arm, 0.7 % in Cycles 1-4, 1.5 % in Cycles 5-8, 1.3 % 
      in Cycles 9-12, and 2.0 % in Cycles >/=13. CONCLUSION: 
      Pemetrexed/pembrolizumab/platinum has manageable toxicity with longer duration of 
      treatment. While the incidence of renal toxicity was slightly higher in the 
      pembrolizumab combination as compared to pemetrexed, the incidence did not 
      increase in later treatment cycles. These results support the safe use of the 
      KEYNOTE-189 regimen in clinical practice. CLINICAL TRIAL REGISTRATION NUMBER: 
      NCT02578680 (clinicaltrials.gov).
CI  - Copyright (c) 2021 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Garon, Edward B
AU  - Garon EB
AD  - David Geffen School of Medicine, University of California Los Angeles, 2825 Santa 
      Monica Blvd, Santa Monica, CA, 90404, USA. Electronic address: 
      egaron@mednet.ucla.edu.
FAU - Aerts, Joachim
AU  - Aerts J
AD  - Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, the 
      Netherlands. Electronic address: j.aerts@erasmusmc.nl.
FAU - Kim, Jong Seok
AU  - Kim JS
AD  - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. 
      Electronic address: kim_jong_seok@lilly.com.
FAU - Muehlenbein, Catherine E
AU  - Muehlenbein CE
AD  - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. 
      Electronic address: muehlenbein_catherine_e@lilly.com.
FAU - Peterson, Patrick
AU  - Peterson P
AD  - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. 
      Electronic address: peterson_patrick@lilly.com.
FAU - Rizzo, Maria Teresa
AU  - Rizzo MT
AD  - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. 
      Electronic address: rizzo_maria_teresa@lilly.com.
FAU - Gadgeel, Shirish M
AU  - Gadgeel SM
AD  - Henry Ford Cancer Institute/Henry Ford Health System, 2799 W Grand Blvd K13, 
      Detroit, MI, 48202, USA. Electronic address: sgadgee1@hfhs.org.
LA  - eng
SI  - ClinicalTrials.gov/NCT02578680
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210219
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 04Q9AIZ7NO (Pemetrexed)
RN  - 49DFR088MY (Platinum)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
EIN - Lung Cancer. 2023 Sep;183:107285. PMID: 37460344
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy
MH  - Humans
MH  - *Lung Neoplasms/drug therapy
MH  - Pemetrexed/adverse effects
MH  - Platinum/therapeutic use
OTO - NOTNLM
OT  - KEYNOTE-189
OT  - NSCLC
OT  - Pembrolizumab
OT  - Pemetrexed
OT  - Safety
EDAT- 2021/03/18 06:00
MHDA- 2021/06/22 06:00
CRDT- 2021/03/17 20:15
PHST- 2020/12/11 00:00 [received]
PHST- 2021/02/11 00:00 [revised]
PHST- 2021/02/15 00:00 [accepted]
PHST- 2021/03/18 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2021/03/17 20:15 [entrez]
AID - S0169-5002(21)00081-7 [pii]
AID - 10.1016/j.lungcan.2021.02.021 [doi]
PST - ppublish
SO  - Lung Cancer. 2021 May;155:53-60. doi: 10.1016/j.lungcan.2021.02.021. Epub 2021 
      Feb 19.