ESMO Congress 2026

Ramucirumab is a monoclonal antibody targeting VEGFR-2 ^[4], and its position in previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma rests on two randomised phase III trials: REGARD assigned patients who progressed after first-line platinum- or fluoropyrimidine-containing chemotherapy 2:1 to ramucirumab monotherapy or placebo (both with best supportive care), with overall survival as the primary endpoint ^[4]; RAINBOW compared ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients progressing on or within 4 months after first-line platinum plus fluoropyrimidine therapy, also with overall survival as the primary endpoint ^[3]. On this evidence, ramucirumab is licensed as anti-angiogenic second-line targeted therapy in gastric cancer, alongside trastuzumab first line in HER2-positive disease and nivolumab or pembrolizumab in the third line, while median survival for advanced gastric cancer after sequential chemotherapy remains less than 1 year ^[2].

What was presented at ESMO26 are the final results of the phase III IKFs602/AIO RAMIRIS study: in taxane-pretreated patients with advanced or metastatic gastroesophageal adenocarcinoma (n=317), second-line FOLFIRI plus ramucirumab was compared head-to-head with paclitaxel plus ramucirumab, with co-primary endpoints of OS and ORR. Median OS was 8.7 vs 7.5 months (HR 0.95, p=0.33) and ORR was 25.3% vs 22.6% (p=0.29), so neither co-primary endpoint was met; median PFS was 5.5 vs 3.7 months (HR 0.7, p=0.003), clearly improved; grade 3-5 adverse events were 70% vs 68%.

Relative to prior knowledge, this readout answers a different question: RAINBOW was placebo-controlled ^[3], whereas in RAMIRIS both arms contained ramucirumab, and the control arm was exactly the ramucirumab plus paclitaxel regimen tested in RAINBOW ^[3], so the real comparison was between chemotherapy backbones - whether switching to FOLFIRI outperforms re-using paclitaxel after prior taxane exposure. On OS and ORR the answer is no, but the PFS signal is clear. Commentators at the meeting noted that not every negative phase III trial is clinically uninformative: FOLFIRI plus ramucirumab may not broadly replace paclitaxel plus ramucirumab, but when prior taxane exposure, neuropathy, toxicity or other patient-specific factors make another taxane less attractive, it is a reasonable alternative, underscoring the value of personalised sequencing.

The limitations are equally clear: the co-primary endpoints were not met, the PFS gain did not translate into an OS difference, and grade 3-5 adverse events were high in both arms (70% vs 68%), with no separation on safety either. The data therefore support flexibility in treatment choice rather than establishing a new standard second-line regimen.