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

Abstract FOLFOX plus nivolumab represents a standard of care for first‐line therapy of advanced gastroesophageal cancer (aGEC) with positive PD‐L1 expression. The efficacy of second‐line VEGFR‐2 inhibition with ramucirumab (RAM) plus chemotherapy after progression to immunochemotherapy remains unclear. Medical records of patients with aGEC enrolled in the randomized phase II AIO‐STO‐0417 trial after treatment failure to first‐line FOLFOX plus nivolumab and ipilimumab were retrospectively analyzed. Patients were divided into two groups based on second‐line therapy: RAM plus chemotherapy (RAM group) or treatment without RAM (control group). Eighty three patients were included. In the overall population, progression‐free survival (PFS) in the RAM group was superior to the control (4.5 vs 2.9 months). Responders (CR/PR) to first‐line immunochemotherapy receiving RAM containing second‐line therapy had prolonged OS from start of first‐line therapy (28.9 vs 16.5 months), as well as second‐line OS (9.6 vs 7.5 months), PFS (5.6 vs 2.9 months) and DCR (53% vs 29%) compared to the control. PD‐L1 CPS ≥1 was 42% and 44% for the RAM and the control, respectively. Patients with CPS ≥1 in the RAM group showed better tumor control (ORR 25% vs 10%) and improved survival (total OS 11.5 vs 8.0 months; second‐line OS 6.5 vs 3.9 months; PFS 4.5 vs 1.6 months) compared to the control. Prior exposure to first‐line FOLFOX plus dual checkpoint inhibition followed by RAM plus chemotherapy shows favorable response and survival rates especially in patients with initial response and positive PD‐L1 expression and has the potential to advance the treatment paradigm in aGEC.