Efficacy of ramucirumab combination chemotherapy as second-line treatment in patients with advanced adenocarcinoma of the stomach or gastroesophageal junction after exposure to checkpoint inhibitors and chemotherapy as first-line therapy within the prospective phase II IKF-S628/AIO-STO-0417 (MOONLIGHT) trial.

Abstract

4043 Background: FOLFOX plus nivolumab has become standard of care for first-line therapy of patients (pts) with advanced gastroesophageal cancer (aGEC). The efficacy of 2nd line VEGF-2 inhibition with ramucirumab (Ram) plus chemotherapy after progression to immunochemotherapy remains unclear. Methods: Medical records of consecutive pts with aGEC enrolled in the multi-centre randomized phase II AIO-STO-0417 trial who had tumor progression after 1st line FOLFOX plus nivolumab and ipilimumab were retrospectively analysed. Pts were divided into two groups based on the subsequent 2nd line therapy: Ram plus chemotherapy (ramucirumab group) or chemotherapy alone (control group). Outcomes were compared between both groups in the overall population and in subgroup analysis according to best response (CR/PR) under 1st line therapy and tumor PD-L1 expression. Results: In total, 83 pts (38 Ram group, 45 control group) were included. The most frequent 2nd line therapy in the Ram group was Ram plus paclitaxel (85%). In the overall population, median progression-free survival (PFS) in the Ram group was longerthan in the control group (4.5 vs. 2.9 months). Responders (CR/PR) to 1st line immunochemotherapy who received Ram containing 2nd line therapy (n = 15) showed a clearly prolonged median OS counted from start of 1st line therapy (28.9 vs. 16.5 months), as well as 2nd line OS (9.6 vs. 7.5 months), PFS (5.6 vs. 2.9 months) and DCR (53% vs. 29%) compared to the control group (n = 24). PD-L1 CPS ≥ 1 (status known for77% of pts) was 42% and 44% for the Ram and the control group, respectively. Patients with CPS ≥ 1 in the Ram group (n = 16) showed a trend towards better tumor control (ORR 25% vs. 10%, DCR 44% vs. 30%) and improved survival (total OS 11.5 vs. 8.0 months; 2nd line OS 6.5 vs. 3.9 months; PFS 4.5 vs. 1.6 months) compared to the control group (n = 20). Conclusions: Ramucirumab is effective as 2nd line treatment after progression on 1st line FOLFOX plus dual checkpoint inhibition, especially in patients with initial response and positive PD-L1 expression. Sequential angiogenesis inhibition with anti-VEGFR-2 targeting therapy following immunochemotherapy might be a promising option to overcome resistance to immunotherapy, which warrants further investigations in a larger cohort. Clinical trial information: NCT03647969 .