Improved efficacy of taxanes and ramucirumab combination chemotherapy after exposure to anti-PD-1 therapy in advanced gastric cancer

Background The efficacy and safety of chemotherapy (CTx) after anti-PD-1 therapy in patients with advanced gastric cancer (AGC) remains unclear. Methods Medical records of consecutive patients with AGC treated with both CTx (taxanes plus ramucirumab, taxanes monotherapy or irinotecan) and anti-PD-1 therapy from June 2015 to April 2019 were retrospectively analysed. Patients were divided into two groups based on prior exposure to anti-PD-1 therapy: anti-PD-1-exposed and anti-PD-1-naive groups. CTx-related outcomes were compared between two groups in the overall population and each CTx population. Results In total, 233 patients (67 anti-PD-1-exposed, 166 anti-PD-1-naive) were included. In the overall population, the objective response rate (ORR) to CTX was 44.6% in the anti-PD-1-exposed group and 19.6% in the anti-PD-1-naive group (p=0.001); the median progression-free survivals (PFS) were 3.7 months and 3.3 months (HR=0.82, p=0.20), respectively. Among patients receiving taxanes plus ramucirumab (n=149), ORR (60.6% vs 20.0%, p<0.001) and median PFS (4.8 vs 3.4 months, p=0.004, HR=0.56) were significantly better in the anti-PD-1-exposed group (n=39) compared with the anti-PD-1-naive group (n=110). These differences were not observed in patients receiving taxane monotherapy (n=34) or irinotecan (n=50). CTx after anti-PD-1 therapy showed no severe or unexpected adverse events. Conclusions Prior anti-PD-1 therapy might increase tumour response to taxanes plus ramucirumab without unexpected adverse events, which warrants further investigations in a large cohort.