PMID- 34607222
OWN - NLM
STAT- MEDLINE
DCOM- 20220310
LR  - 20220310
IS  - 2468-2942 (Electronic)
IS  - 2468-2942 (Linking)
VI  - 29
DP  - 2021
TI  - Phase 1 study of pembrolizumab plus chemotherapy as first-line treatment in 
      Japanese patients with advanced NSCLC.
PG  - 100458
LID - S2468-2942(21)00154-4 [pii]
LID - 10.1016/j.ctarc.2021.100458 [doi]
AB  - INTRODUCTION: Pembrolizumab plus chemotherapy significantly improved outcomes 
      over chemotherapy alone as first-line treatment in patients with advanced 
      non-small-cell lung cancer (NSCLC) in phase 3 international trials. In the phase 
      1 KEYNOTE-011 study (parts B and C), we evaluated the safety/activity of 
      pembrolizumab plus chemotherapy as first-line treatment in Japanese patients with 
      advanced NSCLC. METHODS: Eligible patients received 4 cycles (every 3 weeks) of 
      pembrolizumab 200 mg plus chemotherapy (cisplatin 75 mg/m(2)/carboplatin area 
      under the curve [AUC] 5 mg/mL/min and pemetrexed 500 mg/m(2) in part B 
      [nonsquamous]; carboplatin AUC 6 mg/mL/min and paclitaxel 
      200 mg/m(2)/nab-paclitaxel 100 mg/m(2) (weekly) in part C [squamous]), followed 
      by maintenance pembrolizumab (and pemetrexed, part B). The primary endpoint was 
      incidence of dose-limiting toxicities (DLTs) during the first 3 weeks of 
      treatment. Overall response rate (ORR; RECIST v1.1 by central review) was 
      exploratory. RESULTS: In part B (median follow-up, 16.0 months; n = 12) 1 DLT 
      occurred (grade 4 hyponatremia). Grade >/=3 treatment-related adverse events (AEs) 
      occurred in 9 patients (75%). Two patients had grade 5 treatment-related AEs 
      (pneumonitis and interstitial lung disease). In part C (median follow-up, 9.9 
      months; n = 14), 2 DLTs occurred (both grade 3 febrile neutropenia). Grade >/=3 
      treatment-related AEs occurred in 11 patients (79%); none were fatal. ORR was 73% 
      in part B and 50% in part C, irrespective of PD-L1 status. CONCLUSION: Safety 
      results show first-line pembrolizumab plus chemotherapy is feasible in Japanese 
      patients with advanced NSCLC. Antitumor activity was observed irrespective of 
      PD-L1 status and was comparable to that in international studies. TRIAL REGISTER: 
      ClinicalTrials.gov, NCT01840579.
CI  - Copyright (c) 2021 Merck Sharp & Dohme Corp., The Author(s). Published by Elsevier 
      Ltd.. All rights reserved.
FAU - Kurata, Takayasu
AU  - Kurata T
AD  - Department of Thoracic Oncology, Kansai Medical University Hospital, 2-3-1 
      Shin-machi, Hirakata, Osaka 573-1191, Japan. Electronic address: 
      kuratat@hirakata.kmu.ac.jp.
FAU - Nakagawa, Kazuhiko
AU  - Nakagawa K
AD  - Department of Medical Oncology, Kindai University Faculty of Medicine, 
      Osaka-Sayama, 13-70, Kitaoji-cho, Akashi City, Hyogo 673-8558, Japan.
FAU - Satouchi, Miyako
AU  - Satouchi M
AD  - Department of Thoracic Oncology, Hyogo Cancer Center, 13-70, Kitaoji-cho, Akashi 
      City, Hyogo 673-8558, Japan.
FAU - Seto, Takashi
AU  - Seto T
AD  - Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer 
      Center, 3-1-1 Notame, Minami-ku, Fukuoka 811-1395, Japan.
FAU - Sawada, Takeshi
AU  - Sawada T
AD  - MSD K.K, Kitanomaru Square, 1-13-12, Kudan Kita, Chiyoda-ku, Tokyo 102-8667, 
      Japan.
FAU - Han, Shirong
AU  - Han S
AD  - MSD K.K, Kitanomaru Square, 1-13-12, Kudan Kita, Chiyoda-ku, Tokyo 102-8667, 
      Japan.
FAU - Homma, Masae
AU  - Homma M
AD  - MSD K.K, Kitanomaru Square, 1-13-12, Kudan Kita, Chiyoda-ku, Tokyo 102-8667, 
      Japan.
FAU - Noguchi, Kazuo
AU  - Noguchi K
AD  - MSD K.K, Kitanomaru Square, 1-13-12, Kudan Kita, Chiyoda-ku, Tokyo 102-8667, 
      Japan.
FAU - Nogami, Naoyuki
AU  - Nogami N
AD  - Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer 
      Center, 160 Minami-Umemoto-cho, Matsuyama, 791-0280, Japan.
LA  - eng
SI  - ClinicalTrials.gov/NCT01840579
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210915
PL  - England
TA  - Cancer Treat Res Commun
JT  - Cancer treatment and research communications
JID - 101694651
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/pharmacology/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology
MH  - Female
MH  - Humans
MH  - Japan
MH  - Lung Neoplasms/*drug therapy/pathology
MH  - Male
MH  - Middle Aged
OTO - NOTNLM
OT  - Antineoplastic agents
OT  - Antitumor activity
OT  - Japan
OT  - Non-small-cell lung carcinoma
OT  - Programmed death ligand 1
EDAT- 2021/10/05 06:00
MHDA- 2022/03/11 06:00
CRDT- 2021/10/04 20:26
PHST- 2021/08/11 00:00 [received]
PHST- 2021/09/10 00:00 [revised]
PHST- 2021/09/13 00:00 [accepted]
PHST- 2021/10/05 06:00 [pubmed]
PHST- 2022/03/11 06:00 [medline]
PHST- 2021/10/04 20:26 [entrez]
AID - S2468-2942(21)00154-4 [pii]
AID - 10.1016/j.ctarc.2021.100458 [doi]
PST - ppublish
SO  - Cancer Treat Res Commun. 2021;29:100458. doi: 10.1016/j.ctarc.2021.100458. Epub 
      2021 Sep 15.