Eur J Cancer. 2019;108:17-24.
A phase II, randomised study of mFOLFOX6 with or without the Akt inhibitor ipatasertib in patients with locally advanced or metastatic gastric or gastroesophageal junction cancer.
제1저자 방영주 · 교신저자 Ajani JA
소속 (12)
- Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu Seoul 03080, South Korea. Electronic address: bangyj@snu.ac.kr.
- Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea. Electronic address: ykkang@amc.seoul.kr.
- National Cancer Centre Singapore, Singapore. Electronic address: matthew.ng.c.h@singhealth.com.sg.
- Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Yonsei University Health System, Yonsei-ro 50-1 Seodaemun-gyu Shinchon-dong 134 Seoul 03722, South Korea. Electronic address: unchung8@yuhs.ac.
- David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. Electronic address: ZWainberg@mednet.ucla.edu.
- Genentech, Inc., South San Francisco, CA 94080, USA. Electronic address: gendreau.steven@gene.com.
- Genentech, Inc., South San Francisco, CA 94080, USA. Electronic address: wychan4@gmail.com.
- Genentech, Inc., South San Francisco, CA 94080, USA. Electronic address: xu.na@gene.com.
- Genentech, Inc., South San Francisco, CA 94080, USA. Electronic address: dmaslyar@gmail.com.
- Genentech, Inc., South San Francisco, CA 94080, USA. Electronic address: meng.raymond@gene.com.
- The Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom SM2 5PT UK. Electronic address: ian.chau@rmh.nhs.Uk.
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: jajani@mdanderson.org.
Abstract
BACKGROUND Akt activation is common in gastric/gastroesophageal junction cancer (GC/GEJC) and is associated with chemotherapy resistance. Treatment with ipatasertib, a pan-Akt inhibitor, may potentiate the efficacy of chemotherapy in GC/GEJC.
PATIENTS AND METHODS In this randomised, double-blind, placebo-controlled, multicentre, phase II trial, patients with locally advanced or metastatic GC/GEJC not amenable to curative therapy were randomised 1:1 to receive ipatasertib or placebo, plus mFOLFOX6 (modified regimen of leucovorin, bolus and infusional 5-fluorouracil [5-FU], and oxaliplatin). The co-primary end-point was progression-free survival (PFS) in the intent-to-treat (ITT) population and in phosphatase and tensin homolog (PTEN)-low patients. Secondary end-points included PFS in patients with PI3K/Akt pathway-activated tumours; overall survival, investigator-assessed objective response rate and duration of response in the ITT population; and safety assessments.
RESULTS In 153 enrolled patients, the median PFS (ITT) was 6.6 months (90% confidence interval [CI], 5.7-7.5) with ipatasertib/mFOLFOX6 versus 7.5 months (90% CI, 6.2-8.1) with placebo/mFOLFOX6 (hazard ratio, 1.12; 90% CI, 0.81-1.55; P = 0.56). No statistically significant PFS benefit was observed in biomarker-selected patient subgroups (PTEN-low and PI3K/Akt pathway-activated tumours) with ipatasertib/mFOLFOX6 versus placebo/mFOLFOX6. Other secondary end-points did not favour the ipatasertib/mFOLFOX6 treatment arm. The percentages of patients with ≥1 adverse event (AE, 100% versus 98%) and grade ≥3 AEs (79% versus 74%) were similar between arms. Higher rates of AEs leading to treatment withdrawal (16% versus 6%) and serious AEs were reported in the ipatasertib arm (54% versus 43%). Thirty-nine and 29 deaths occurred in the ipatasertib and placebo arms, respectively.
CONCLUSIONS Ipatasertib/mFOLFOX6 compared with placebo/mFOLFOX6 did not improve PFS in unselected or biomarker-selected patients. No unexpected safety concerns were observed.
TRIAL REGISTRATION ClinicalTrials.gov (NCT01896531).
Copyright © 2018 Elsevier Ltd. All rights reserved.
Keywords
Akt inhibitorGastric cancerGastroesophageal junction cancerIpatasertibmFOLFOX6
그 밖의 정보
- 출판 형태
- Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
- 저널
- European journal of cancer (Oxford, England : 1990) · eISSN 1879-0852
- 전자 출판
- 2018-12-25
- MeSH
- Adult · Aged · Aged, 80 and over · Antineoplastic Combined Chemotherapy Protocols / therapeutic use · Bone Neoplasms / drug therapy / secondary · Carcinoma / drug therapy / secondary · Esophagogastric Junction* · Female · Fluorouracil / therapeutic use · Humans · Leucovorin / therapeutic use · Liver Neoplasms / drug therapy / secondary · Lung Neoplasms / drug therapy / secondary · Lymph Nodes / pathology · Male · Middle Aged · Organoplatinum Compounds / therapeutic use · Piperazines / therapeutic use · Progression-Free Survival · Proto-Oncogene Proteins c-akt / antagonists & inhibitors · Pyrimidines / therapeutic use · Stomach Neoplasms / drug therapy / pathology
- Substances
- Organoplatinum Compounds · Piperazines · Pyrimidines · ipatasertib · Proto-Oncogene Proteins c-akt · Leucovorin · Fluorouracil
- 데이터
- ClinicalTrials.gov: NCT01896531