1424P - Maintenance capecitabine plus ramucirumab after first-line platinum-based chemotherapy in advanced oesophagogastric adenocarcinoma (OGA): Final analysis from the PLATFORM trial

Background

PLATFORM, a prospective, open-label, multi-centre, adaptive phase II trial assessed maintenance therapy in patients (pts) with advanced OGA after platinum-based first-line induction chemotherapy. We report HER2-negative pts randomised 1:1 to surveillance (control) or maintenance capecitabine plus ramucirumab (cape-ram).

Methods

After 18 weeks of platinum-based chemotherapy, pts with response or stable disease were randomised. Pts had 4- weekly surveillance visits or maintenance cape-ram on day 1 and 8 of a 21-day cycle to progression, death or toxicity. Primary endpoint was progression-free survival (PFS): randomisation to progression or death (pre-specified one-sided p-value 0.025). Key secondary endpoints: overall survival (OS), toxicity. The trial arm closed early in November 2022 due to withdrawal of industry support.

Results

47 pts were randomised. At data cut-off 28 March 2024, 25 control and 22 cape-ram pts were in intention-to- treat (ITT) population. Median follow up was 24.4 mo. Median PFS was 2.5 mo in control arm vs 5.5 mo in cape-ram arm (HR 0.33, 95% CI 0.17 – 0.63, p <0.001) and 6 mo PFS rate was 4% (95% CI 0.3-17.0) vs 42.9% (95% CI 21.9 – 62.3) respectively. Median OS from randomisation of maintenance therapy was 7.1 mo in control arm vs 14.4 mo in cape-ram arm (HR 0.51, 95% CI 0.26-1.00, p=0.025) and median OS from start of induction chemotherapy was 12.1 mo in control arm vs 19.5 mo in cape-ram arm. Of 10 cape-ram pts with measurable disease, 1 had an incremental partial response. 25 control and 21 cape-ram pts were in the safety population. Grade ≥3 adverse events (AEs) were 32% in control arm vs 57% in cape-ram arm. Six cape-ram pts had grade 3 treatment related AEs; hypertension (14%) thromboembolism (10%), anaemia (5%) and hand-foot syndrome (5%). No grade 4+ related AEs or new safety signals were identified.

Conclusions

Maintenance cape-ram after first-line platinum-based chemotherapy for HER2-negative pts significantly improves survival compared to surveillance. To our knowledge, this is the first maintenance study demonstrating survival benefit and should be considered a new option for pts who have not had first-line chemo-immunotherapy.

Clinical trial identification

EudraCT: 2014-002169-30, First opened February 2018.

Editorial acknowledgement

Legal entity responsible for the study

The Royal Marsden GI/Lymphoma Unit.

Funding

Eli Lilly.

Disclosure

C.Y.K. Fong: Financial Interests, Other, Honoraria: BMS. M. Davidson: Financial Interests, Speaker, Consultant, Advisor: Takeda. N.R. Maisey: Financial Interests, Funding: BMS, MSD, Servier. S. Darby: Financial Interests, Invited Speaker: Servier, BMS. T.S. Waddell: Financial Interests, Other, Honoraria, Advisory, Research Funding: Pfizer; Financial Interests, Other, Honoraria, Advisory, Research Funding, Travel/accommodation expenses: BMS, EUSA Pharma; Financial Interests, Other, Advisory, Research Funding: Roche, Eisai Europe; Financial Interests, Other, Advisory, Research Funding,: Merck Sharp & Dohme; Financial Interests, Other, Research Funding, Travel/accommodation: Ipsen. N. Starling: Financial Interests, Personal, Advisory Board: GSK, Novartis, MSD Oncology, Servier, AstraZeneca, Pfizer, Gilead Sciences, Seagen, Janssen, Takeda, Moderna, BMS; Financial Interests, Personal, Invited Speaker: Eli Lilly, Pierre Fabre, Amgen, Merck Serono, Novartis, MSD Oncology, GSK, Servier, Seagen, BMS, AstraZeneca, Astellas; Financial Interests, Institutional, Research Grant, Sept 2017 (24m) Paid to institution research: Merck; Financial Interests, Institutional, Research Grant, Nov 2017 (48m) -Paid to institution research fund: AstraZeneca; Financial Interests, Institutional, Research Grant, Jan 2018 - Paid to institution research fund: Pfizer; Financial Interests, Institutional, Research Grant, July 2018 (36m) Paid to institution research fund: BMS; Financial Interests, Institutional, Research Grant, June 2022 - Paid to institution research fund: Guardant; Financial Interests, Institutional, Research Grant, August 2023 - Paid to institution research fund: Gilead; Non-Financial Interests, Advisory Role, Ad Board uncompensated: Guardant. I. Chau: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Eli Lilly, MSD, Roche, Merck-Serono, AstraZeneca, OncXerna, Astella, Incyte, GSK, Sotio, Daiichi Sankyo, Eisai, Taiho, Seagen, Turning Point Therapeutics, Novartis, Takeda, Elevation Oncology; Financial Interests, Personal, Invited Speaker: Eisai, Eli Lilly, Servier, Roche; Financial Interests, Institutional, Coordinating PI: Cilag-Janssen, Eli Lilly. D. Cunningham: Financial Interests, Research Grant: Clovis, Eli Lilly, 4SC, Bayer, Celgene, NIHR EME, Roche; Financial Interests, Other, IMP drug supply: Leap; Financial Interests, Advisory Board: Ovibio. All other authors have declared no conflicts of interest.