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-naïve 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-naïve) 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-naïve 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-naïve 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.