LBA58 - A randomized phase III trial of perioperative chemotherapy (periop CT) with or without preoperative chemoradiotherapy (preop CRT) for resectable gastric cancer (AGITG TOPGEAR): Final results from an intergroup trial of AGITG, TROG, EORTC and CCTG

Background

In Western countries, the current standard of care for resectable gastric cancer is periop CT. There is much interest in preop CRT, but comparison to periop CT alone is lacking. In TOPGEAR we hypothesized that adding preop CRT to periop CT would improve pathological complete response (pCR) rates and ultimately overall survival (OS) compared to periop CT alone.

Methods

This international phase 3 trial randomized patients with resectable adenocarcinoma of the stomach and gastro-esophageal junction to periop CT alone, or with preop CRT. The periop CT alone group received 3 cycles of epirubicin/cisplatin/5-fluorouracil (ECF) or 4 cycles of fluorouracil/leucovorin/oxaliplatin/docetaxel (FLOT) both pre- and post-operatively. The preop CRT group received one less cycle of preop chemotherapy followed by chemoradiotherapy (45 Gy in 25 fractions radiation plus infusional 5-FU ), and then the same postop chemotherapy. The primary endpoint was overall survival, and secondary endpoints included progression free survival (PFS), pCR rates, toxicity and quality of life.

Results

Between September 2009 and May 2021, 574 patients were enrolled from 70 sites across 15 countries in Australasia, Europe, and Canada; 288 to periop CT group and 286 to preop CRT group. Compared to periop CT alone, patients receiving preop CRT achieved a higher pCR rate (16.7% vs 8.0%), a higher rate of major pathological response (0 - <10% residual tumor: 49.5% vs 29.3%), and greater tumor downstaging following resection. After a median follow-up of 66.7 months, there was no significant difference in OS or PFS: median OS periop CT 49.4 months vs preop CRT 46.4 months; median PFS periop CT 31.8 months vs preop CRT 31.4 months. Preop CRT was not associated with increased perioperative treatment toxicity or a higher rate of surgical complications.

Conclusions

Despite improving pathological outcomes, the addition of preop CRT to periop CT does not improve overall survival compared to periop CT alone in patients with resectable gastric and gastro-esophageal junction adenocarcinoma.

Clinical trial identification

ACTRN12609000035224. Registered 30 May 2009; NCT01924819.

Editorial acknowledgement

Legal entity responsible for the study

Australasian Gastro-Intestinal Trials Group (AGITG).

Funding

This work was supported by grants from the National Health and Medical Research Council: 1046425 and 2000711, Canadian Institutes of Health Research (CIHR) grant no. 119445, the Canadian Cancer Society Research Institute (CCSRI) grant no. 021039, the Health Research Council of New Zealand (HRC) International Investment Opportunities Fund: Contract no. 09/624, the EORTC Cancer Research Fund, and the Cancer Australia Priority-driven Collaborative Research Scheme: Project ID: 570996.

Disclosure

K.M. Haustermans: Financial Interests, Personal, Other, Clinical editor Radiotherapy & Oncology: Elsevier; Financial Interests, Institutional, Funding: IBA; Financial Interests, Institutional, Research Grant: Varian, RaySearch. R. Wong: Other, Personal, Other, expert panel in radiotheranostics: Novartis; Non-Financial Interests, Institutional, Local PI: precirix; Non-Financial Interests, Institutional, Other, education grant: Bruce power. J.R. Zalcberg: Financial Interests, Personal, Advisory Board: MSD, FiveFusion, Duo Oncology, RevMed; Financial Interests, Institutional, Other, Research: MSD, BMS, Astellas, Taiho, Servier, STA; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Writing Engagement: Servier; Financial Interests, Personal, Member of Board of Directors, NED: ICON, PRAXIS; Financial Interests, Personal, Stocks/Shares: Biomarin, Amarin, Ophthea, Frequency Therapeutics, Gilead, UniQure, Orphazyme, Novavax, CSL; Non-Financial Interests, Member of Board of Directors, Australian Clinical Trials Alliance: ACTA. A. Boussioutas: Financial Interests, Personal, Invited Speaker, Company meeting invited speaker, speakers bureau: AbbVie; Financial Interests, Institutional, Full or part-time Employment, Employee of this health service: Alfred Health; Financial Interests, Institutional, Full or part-time Employment, Employee of the University as Professor of Gastroenterology: Monash University; Non-Financial Interests, Member of Board of Directors, Chair of the Board and President: Gastroenterology Society of Australia; Non-Financial Interests, Advisory Role, On Clinical Advisory Committee (unpaid): Lifeblood; Non-Financial Interests, Member: American Gastroenterology Association. M. Findlay: Financial Interests, Personal, Ownership Interest, private healthcare provider - ownership shares sold February 2014 - no remaining interest: Canopy Cancer Care (New Zealand); Non-Financial Interests, Member of Board of Directors, not for profit organisation promoting awareness, fundraising for and funding research into Gastro-Intestinal Cancers: Gut Cancer Foundation (New Zealand). A. Moore: Financial Interests, Institutional, Full or part-time Employment, Employed at the TROG Radiation Therapy Manager: Trans Tasman Radiation Oncology. F. Lordick: Financial Interests, Personal, Advisory Board: Astellas, BMS, BeiGene, Biontech, MSD, Daiichi Sankyo, Page; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Eli Lilly, Imedex, Incyte, MSD, MedUpdate, Medscape, Merck Serono, Servier, StreamedUp!, Daiichi Sankyo, Art Tempi, Astellas; Financial Interests, Personal, Writing Engagement: Deutscher Ärzteverlag, Elsevier, Iomedico; Financial Interests, Institutional, Research Grant: BMS, Gilead, AstraZeneca; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, BeiGene. G.E. Darling: Financial Interests, Personal, Invited Speaker, Honorarium 2023, $2000: BMS; Financial Interests, Personal, Stocks/Shares, stocks in multiple companies managed funds - I do not direct buying or selling of shares: multiple. M. Liberman: Financial Interests, Personal, Advisory Board: Johnson & Johnson, SherMATRIX, Sparrow, Noah Medical, J&J - Lung Cancer Initiative; Financial Interests, Personal, Stocks/Shares, CMO: Endocision, AssistIQ, Ditch Labs; Financial Interests, Institutional, Other, Radio-Opaque Marker and System for Tumourous Tissue - Sting-MarkPatent number: 10249569-94USPR: Patent; Financial Interests, Institutional, Other, Intragastric Balloon System - Endoscopic Sleeve Gastrectomy (ESG) BalloonPatent number: 10249569-96USPR: Patent; Financial Interests, Institutional, Other, Attachment System for Endoscopes - Cryo CorsetPatent numbers: CA3178623A1 - Canadian applicationUS20230172436A1 - US applicationEP4149342A1 - European application: Patent; Financial Interests, Local PI: Merck, AstraZeneca, Pfizer, BMS; Financial Interests, Research Grant: J&J; Financial Interests, Institutional, Research Grant, Research and Educational Grant: Boston Scientific, Olympus, Intuitive, Novartis, Broncus, Roche, POINT Biopharma, Galvanize Therapeutics, Caprion, ODS Medical. L. Mineur: Financial Interests, Personal, Advisory Board, Œsophagus carcinoma Treatment preoperative what strategy ?Congress intervention symposium congress of the Sfro in 2023 french congress in radiotherapy: Bms; Non-Financial Interests, Advisory Board, Develop patient oostomy expertise in care patwaysPatient assistance: Association oostomy Provence contact. J. Simes: Financial Interests, Institutional, Advisory Board, Advisory Board Member: Detsamma FivepHusion; Financial Interests, Institutional, Research Grant, Research funding for clinical trials: Bayer, Roche; Financial Interests, Institutional, Research Grant, Research Funding for Clinical Trials: BMS, MSD, AstraZeneca, Pfizer. All other authors have declared no conflicts of interest.