Improved efficacy of taxanes and ramucirumab combination chemotherapy after exposure to anti-PD-1 therapy in advanced gastric cancer
Akinori Sasaki, Akihito Kawazoe, Testuya Eto, Mashiro Okunaka, Saori Mishima, Kentaro Sawada, Yoshiaki Nakamura, Daisuke Kotani, Yasutoshi Kuboki, Hiroya Taniguchi, Takashi Kojima, Toshihiko Doi, Takayuki Yoshino, Tetsuo Akimoto, Kohei Shitara
Abstract
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.