Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: Primary analysis of JAVELIN Gastric 300

Y. J. Bang, E. Yañez Ruiz, E. Van Cutsem, K. W. Lee, L. Wyrwicz, M. Schenker, M. Alsina, M. H. Ryu, H. C. Chung, L. Evesque, S. E. Al-Batran, S. H. Park, M. Lichinitser, N. Boku, M. H. Moehler, J. Hong, H. Xiong, R. Hallwachs, I. Conti, J. Taieb

Research output: Contribution to journalArticlepeer-review

158 Citations (Scopus)

Abstract

Background: There currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/ gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician's choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC. Patients and methods: Patients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10 mg/kg by intravenous infusion every 2 weeks or physician's choice of chemotherapy (paclitaxel 80 mg/m2 on days 1, 8, and 15 or irinotecan 150 mg/m2 on days 1 and 15, each of a 4-week treatment cycle); patients ineligible for chemotherapy received best supportive care. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. Results: A total of 371 patients were randomised. The trial did not meet its primary end point of improving OS {median, 4.6 versus 5.0 months; hazard ratio (HR)¼1.1 [95% confidence interval (CI) 0.9-1.4]; P ¼ 0.81} or the secondary end points of PFS [median, 1.4 versus 2.7 months; HR¼1.73 (95% CI 1.4-2.2); P > 0.99] or ORR (2.2% versus 4.3%) in the avelumab versus chemotherapy arms, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 90 patients (48.9%) and 131 patients (74.0%) in the avelumab and chemotherapy arms, respectively. Grade 3 TRAEs occurred in 17 patients (9.2%) in the avelumab arm and in 56 patients (31.6%) in the chemotherapy arm. Conclusions: Treatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared with chemotherapy. Avelumab showed a more manageable safety profile than chemotherapy.

Original languageEnglish
Pages (from-to)2052-2060
Number of pages9
JournalAnnals of Oncology
Volume29
Issue number10
DOIs
Publication statusPublished - 2018 Oct

Bibliographical note

Funding Information:
This work was supported by Merck KGaA, Darmstadt, Germany, and is part of an alliance between Merck KGaA and Pfizer Inc., New York, NY, USA. Medical writing support was provided by ClinicalThinking, Inc., Hamilton, NJ, USA, and funded by Merck KGaA, and Pfizer Inc. No grant number is applicable.

Funding Information:
Y-JB reports consultancy or advisory role with ADC Therapeutics, AstraZeneca, Bayer, Bristol-Myers Squibb, Eli Lilly, Five Prime Therapeutics, Genentech/Roche, Green Cross, Merck Serono, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, and Samyang Biopharm; and research funding from AstraZeneca, Bayer, BeiGene, Boehringer-Ingelheim, Boston Biomedical, Bristol-Myers Squibb, CKD, Curis, Daiichi Sankyo, Eli Lilly, Five Prime Therapeutics, Genentech/Roche, GlaxoSmithKline, Green Cross, Hanmi, MacroGenics, Merck Serono, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Otsuka, Pfizer, Takeda, and Taiho Pharmaceutical. EVC reports research funding from Amgen, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ipsen, Merck, Merck KGaA, Novartis, Roche, and Servier. K-WL reports consultancy or advisory role with Merck KGaA, and Sanofi/Aventis; and research funding from AstraZeneca/MedImmune, Daiichi Sankyo, Five Prime Therapeutics, Green Cross, MacroGenics, Merck KGaA, Merck Sharp & Dohme, Ono Pharmaceutical, and Taiho Pharmaceutical. LW reports consultancy or advisory role with Amgen, Eisai, Halozyme, and Roche; speaker services for Amgen, Roche, and Sanofi; and travel, accommodations, or expenses from Roche and Servier. MS reports personal fees from AbbVie, Astellas, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Mylan, Novartis, Pfizer, and Roche. M-HR reports honoraria from Bristol-Myers Squibb, Dae Hwa Pharmaceutical, Eli Lilly, and Ono Pharmaceutical; and consultancy or advisory with Bristol-Myers Squibb, Dae Hwa Pharmaceutical, Eli Lilly, and Ono Pharmaceutical. HCC reports consultancy or advisory role with Bristol-Myers Squibb, Celltrion, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Quintiles, and Taiho Pharmaceutical; research funding from Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck Serono, Merck Sharp & Dohme, Ono Pharmaceutical, and Taiho Pharmaceutical; and speaker services for Eli Lilly, Merck Serono, and Foundation Medicine. S-EA-B reports consultancy or advisory role with Bristol-Myers Squibb, Celgene, Eli Lilly, Merck, Merck Sharp & Dohme, Nordic Pharma, and Roche; speaker services for AIO gGmbH, Celgene, Eli Lilly, Forum für Medizinische Fortbildung, MCI, Nordic Pharma, Promedicis, and Roche; is the CEO/Founder of IKF Klinische Krebsforschung GmbH; and research funding from Celgene, Eli Lilly, Federal Ministry of Education of Research, German Cancer Aid (Krebshilfe), German Research Foundation, Hospira, Medac, Merck, Roche, Sanofi, and Vifor. NB reports honoraria from Chugai Pharma, Eli Lilly, Merck KGaA, Ono Pharmaceutical, Shionogi Pharma, Taiho Pharmaceutical, and Yakult Honsha, and his institution has received research grants from Bristol-Myers Squibb, Ono Pharmaceutical, and Taiho Pharmaceutical. MHM reports consultancy or advisory fees and speaker services for Amgen, Bayer, Merck & Co, Merck KGaA, and Roche and has received travel expenses from Amgen, Merck KGaA, and Pfizer. JH and HX and are employees of EMD Serono, a company of Merck KGaA, Darmstadt, Germany. JH reports personal fees from EMD Serono during the conduct of the study and outside the submitted work. RH is an employee of Merck KGaA, Darmstadt. IC is an employee of EMD Serono and owns stock in Eli Lilly. JT reports honoraria from Amgen, Baxalta, Celgene, Eli Lilly, Merck KGgA, Roche/Genentech, Sanofi, and Servier; consultancy or advisory role with Amgen, Baxalta, Celgene, Eli Lilly, Merck KGgA, Roche/Genentech, Sanofi, and Servier; and travel, accommodations, or expenses from Amgen, Baxalta, Celgene, Eli Lilly, Merck KGgA, Roche/ Genentech, Sanofi, and Servier. All remaining authors have declared no conflicts of interest.

Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

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