1574P - Trastuzumab deruxtecan versus ramucirumab and paclitaxel as second-line therapy for patients with her2-positive gastric or gastro-esophageal junction adenocarcinoma: A propensity score matched comparison

Background

The single arm phase II DESTINY-Gastric02 (DG-02) study investigated the objective response rate, overall survival (OS) and safety of patients treated with Trastuzumab Deruxtecan (T-DXd) as second-line therapy in Western patients with HER2+ unresectable or metastatic gastric or gastro-esophageal junction (GEJ) adenocarcinoma who progressed during or after trastuzumab-based first-line therapy. As the DG-02 study had no control group, the aim of the current study was to compare patients in the DG-02 study to a real-world reference group treated with Ramucirumab and Paclitaxel (Ram+Pac) as second-line therapy.

Methods

DG-02 patients who received trastuzumab in a non-metastatic setting (N=8) were excluded, due to absence of similarly treated patients in the Netherlands Cancer Registry (NCR). All other DG-02 patients (N=71) were included. A comparable set of patients with HER2+ esophageal, gastric or GEJ adenocarcinoma who received trastuzumab in first-line and Ram+Pac in second-line settings were identified from the NCR (N=120). Propensity score trimming (exclusion of patients at the extremes of the propensity score) and propensity score matching based on sex, age, performance status, primary tumor location, BMI, renal function, number of metastatic sites, presence of liver metastases, and duration of first-line treatment were used to select a reference group for the DG-02.

Results

Propensity score trimming resulted in exclusion of 12 DG-02 and 33 NCR patients. Thereafter, propensity score matching resulted in a balanced group of patients from the NCR (N=78) and DG-02 (N=58). Median OS was significantly longer among patients treated with T-DXd (11.6 months, 95%CI: 9.0-20.5) compared to the Ram+Pac group (6.2 months, 95%CI: 4.5 – 10.0) (HR: 0.39, 95%CI: 0.26 –0.59, p<0.0001).

Conclusions

Compared to propensity score-matched patients with metastatic, trastuzumab-pretreated HER2+ gastric or GEJ adenocarcinomas who received Ram+Pac in the real-world as a second -line therapy, overall survival was better for patients who received T-DXd. Due to the nature of the comparison, the results should be interpreted with caution.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Amsterdam University Medical Centers.

Funding

Daiichi Sankyo.

Disclosure

R.H.A. Verhoeven: Financial Interests, Institutional, Advisory Board, Consultancy: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Non-Financial Interests, Member of Board of Directors, The Dutch Upper-GI Cancer Group is the Dutch multidisciplinary research group regarding Upper-GI cancers.: Dutch Upper-GI Cancer Group; Non-Financial Interests, Member of Board of Directors: Internation Association of Cancer Registries. F. Lordick: Financial Interests, Personal, Advisory Board: Amgen, Astellas, BMS, Bayer, BeiGene, Eli Lilly, MSD, Novartis, Roche, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Deutscher Ärzteverlag, Eli Lilly, Imedex, Incyte, Iomedico, MSD, MedUpdate, Medscape, Merck, Roche, Servier, Springer-Nature, StreamedUp!, Daiichi Sankyo, Novartis, Art Tempi; Financial Interests, Personal, Expert Testimony: Biontech, Elsevier; Financial Interests, Institutional, Research Grant: BMS, Gilead. M. Slingerland: Financial Interests, Institutional, Advisory Board: Lilly, Bristol Myers Squibb, AstraZeneca. A. Qin: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc.; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo, inc. H.W.M. van Laarhoven: Financial Interests, Institutional, Advisory Board: BMS, MSD; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Nordic Pharma, Servier; Financial Interests, Institutional, Research Grant, REPEAT study: Bayer; Financial Interests, Institutional, Research Grant: BMS, Philips; Financial Interests, Institutional, Invited Speaker, FRACTION study: BMS; Financial Interests, Institutional, Research Grant, ACTION study: Celgene; Financial Interests, Institutional, Research Grant, DECO study: Janssen; Financial Interests, Institutional, Invited Speaker, RAINFALL study: Lilly; Financial Interests, Institutional, Invited Speaker, KEYNOTE 062 and KEYNOTE 181 study: Merck/MSD; Financial Interests, Institutional, Research Grant, SOX study: Nordic Pharma; Financial Interests, Institutional, Research Grant, TRAP study, PERFECT study; local PI of JACOB study: Roche; Financial Interests, Institutional, Research Grant, LyRICX study: Servier; Financial Interests, Institutional, Research Grant, TAPESTRY study: Merck; Financial Interests, Institutional, Research Grant, Research money and investigational product: Incyte; Non-Financial Interests, Institutional, Product Samples, For all clinical study mentioned, study medication is provided: See 'research funding'. All other authors have declared no conflicts of interest.