PMID- 30366938
OWN - NLM
STAT- MEDLINE
DCOM- 20190703
LR  - 20190703
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 25
IP  - 8
DP  - 2019 Apr 15
TI  - A Multicenter Phase II Study of AMG 337 in Patients with MET-Amplified 
      Gastric/Gastroesophageal Junction/Esophageal Adenocarcinoma and Other 
      MET-Amplified Solid Tumors.
PG  - 2414-2423
LID - 10.1158/1078-0432.CCR-18-1337 [doi]
AB  - PURPOSE: MET gene amplification is associated with poor prognosis in 
      gastric/gastroesophageal junction/esophageal (G/GEJ/E) cancers. We determined 
      antitumor activity, safety, and pharmacokinetics of the small-molecule MET 
      inhibitor AMG 337 in MET-amplified G/GEJ/E adenocarcinoma or other solid 
      tumors.Patients and Methods: In this phase II, single-arm study, adults with 
      MET-amplified G/GEJ/E adenocarcinoma (cohort 1) or other MET-amplified solid 
      tumors (cohort 2) received AMG 337 300 mg/day orally in 28-day cycles. The 
      primary endpoint was objective response rate (ORR; cohort 1). Secondary endpoints 
      included ORR (cohort 2), progression-free survival (PFS), overall survival (OS), 
      and safety. RESULTS: Of 2101 patients screened for MET amplification, 132 were 
      MET-amplified and 60 were enrolled: 45 in cohort 1, and 15 in cohort 2. Fifty-six 
      patients (97%) had metastatic disease; 57 had prior lines of therapy (1 prior 
      line, 29%; >/=2 prior lines, 69%). A protocol-permitted review showed efficacy that 
      was lower-than-expected based on preliminary data from a first-in-human study, 
      and enrollment was stopped. Fifty-eight patients received >/=1 AMG 337 dose. ORR in 
      cohort 1 was 18% (8 partial responses). No responses were observed in cohort 2. 
      Of 54 evaluable patients, median (95% CI) PFS and OS were 3.4 (2.2-5.0) and 7.9 
      (4.8-10.9) months, respectively. The most frequent adverse events (AEs) were 
      headache (60%), nausea (38%), vomiting (38%), and abdominal pain, decreased 
      appetite, and peripheral edema (33% each); 71% had grade >/=3 AEs and 59% had 
      serious AEs. CONCLUSIONS: AMG 337 showed antitumor activity in MET-amplified 
      G/GEJ/E adenocarcinoma but not in MET-amplified non-small-cell lung cancer.See 
      related commentary by Ma, p. 2375.
CI  - (c)2018 American Association for Cancer Research.
FAU - Van Cutsem, Eric
AU  - Van Cutsem E
AD  - Department of Digestive Oncology, University Hospitals Gasthuisberg, Leuven, and 
      KU Leuven, Leuven, Belgium. eric.vancutsem@uzleuven.be.
FAU - Karaszewska, Boguslawa
AU  - Karaszewska B
AD  - Department of Oncology, Przychodnia Lekarska NZOZ KOMED, Konin, Poland.
FAU - Kang, Yoon-Koo
AU  - Kang YK
AD  - Department of Oncology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, South Korea.
FAU - Chung, Hyun Cheol
AU  - Chung HC
AD  - Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College 
      of Medicine, Seoul, South Korea.
FAU - Shankaran, Veena
AU  - Shankaran V
AD  - Division of Medical Oncology, University of Washington, Seattle, Washington.
FAU - Siena, Salvatore
AU  - Siena S
AUID- ORCID: 0000-0002-2681-2846
AD  - Department of Hematology and Oncology, Niguarda Cancer Center, Grande Ospedale 
      Metropolitano Niguarda and Dipartimento di Oncologia and Emato-Oncologia, 
      Universita degli Studi di Milano, Milan, Italy.
FAU - Go, Ning F
AU  - Go NF
AD  - Clinical Biomarkers and Diagnostics, Amgen Inc., Thousand Oaks, California.
FAU - Yang, Hui
AU  - Yang H
AUID- ORCID: 0000-0002-5088-046X
AD  - Global Biostatistical Sciences, Amgen Inc., Thousand Oaks, California.
FAU - Schupp, Marco
AU  - Schupp M
AD  - Global Development, Amgen (Europe) GmbH, Zug, Switzerland.
FAU - Cunningham, David
AU  - Cunningham D
AD  - Department of Medicine, Royal Marsden Hospital, London, United Kingdom.
LA  - eng
PT  - Journal Article
DEP - 20181026
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (AMG 337)
RN  - 0 (Pyridones)
RN  - 0 (Triazoles)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
CIN - Clin Cancer Res. 2019 Apr 15;25(8):2375-2378. PMID: 30770350
MH  - *Adenocarcinoma
MH  - Adult
MH  - Antineoplastic Combined Chemotherapy Protocols
MH  - *Carcinoma, Non-Small-Cell Lung
MH  - Disease-Free Survival
MH  - Esophagogastric Junction
MH  - Fluorouracil
MH  - Humans
MH  - *Lung Neoplasms
MH  - Pyridones
MH  - *Stomach Neoplasms
MH  - Triazoles
EDAT- 2018/10/28 06:00
MHDA- 2019/07/04 06:00
CRDT- 2018/10/28 06:00
PHST- 2018/04/30 00:00 [received]
PHST- 2018/09/26 00:00 [revised]
PHST- 2018/10/22 00:00 [accepted]
PHST- 2018/10/28 06:00 [pubmed]
PHST- 2019/07/04 06:00 [medline]
PHST- 2018/10/28 06:00 [entrez]
AID - 1078-0432.CCR-18-1337 [pii]
AID - 10.1158/1078-0432.CCR-18-1337 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2019 Apr 15;25(8):2414-2423. doi: 10.1158/1078-0432.CCR-18-1337. 
      Epub 2018 Oct 26.