Ramucirumab, Avelumab, and Paclitaxel as Second-Line Treatment in Esophagogastric Adenocarcinoma

• DOI: 10.1001/jamanetworkopen.2023.52830
• Publication Date: 2024-01-23T16:04:48Z
• Authors: Peter Thuss-Patience; Anica Högner; Eray Goekkurt; Michael Stahl; Albrecht Kretzschmar; Thorsten Götze; Gertraud Stocker; Peter Reichardt; Frank Kullmann; Daniel Pink; Prisca Bartels; Armin Jarosch; Axel Hinke; Christoph Schultheiß; Lisa Paschold; Alexander Stein; Mascha Binder
• Keywords: Ramucirumab; Avelumab; Tolerability

Importance Adding immune checkpoint inhibitors to chemotherapy has been associated with improved outcomes in metastatic esophagogastric adenocarcinoma, but treatment combinations and optimal patient selection need be established. Objective To investigate the efficacy tolerability of programmed cell death ligand 1 (PDL-1) inhibitor avelumab paclitaxel plus ramucirumab. Design, Setting, Participants This multicenter, single-group, phase 2 nonrandomized controlled trial was conducted among patients second-line adenocarcinoma. Patients pretreated platinum fluoropyrimidine between April 2019 November 2020 across 10 German centers (median follow-up, 27.4 months [95% CI 22.0-32.9 months]) were included. Data analysis performed from January December 2022. Interventions received ramucirumab at 8 mg/kg on days 15, 80 mg/m 1, 8, 15 every 4 weeks. Main Outcomes Measures The prespecified primary end point overall survival (OS) rate 6 months, experimental therapy considered insufficiently active an OS 50% or less a promising candidate 65% greater. Results Of 60 enrolled patients, 59 [range] age, 64 [18-81] years; 47 males [70.7%]) evaluable, including 30 adenocarcinoma stomach 29 gastroesophageal junction. All fluoropyrimidine, 40 (67.8%) had prior taxanes; 24 56 evaluable (42.9%) PDL-1 combined positive score (CPS) 5 greater, centrally assessed. 71.2% (95% CI, 61.5%-83.7%). median intention-to-treat population (59 patients) 10.6 8.4-12.8 months) overall. Among assessable by central pathology, 9.4 7.2-11.7 32 CPS than 14.0 6.0-22.1 greater ( P = .25). Treatment generally well tolerated, without unexpected toxicities. higher vs lower T repertoire richness showed increased 20.4 7.7-33.0 compared 8.3 3.7-12.9 months; hazard ratio, 0.43; 95% 0.23-0.81; .008). cell-free DNA burden 19.2 8.9-29.6 7.3 3.2-11.4 0.30; 0.16-0.59; < .001). Conclusions relevance In this study, combination favorable for A level median, OS. Trial Registration ClinicalTrials.gov Identifier: NCT03966118