Thus, the current study only generates a hypothesis. 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, Phenformin hydrochloride HR=0.56) were significantly better in the anti-PD-1-exposed group (n=39) compared with the anti-PD-1-na?ve 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. strong class=”kwd-title” Keywords: Gastric cancer, anti-PD-1 therapy, chemotherapy, ramucirumab, taxanes, irinotecan Key questions What is already known about this subject? Anti-PD-1 therapy might improve responses to subsequent chemotherapy without unexpected safety signals in patients with several cancers. The efficacy and safety of chemotherapy after anti-PD-1 therapy in Phenformin hydrochloride patients with advanced gastric cancer remains unclear. What does this study add? We assessed the tumour response to chemotherapy including taxanes plus ramucirumab, taxanes monotherapy, or irinotecan and toxicities in patients with advanced gastric cancer, with or without prior exposure to anti-PD-1 therapy. How might this impact on clinical practice? Prior exposure to anti-PD-1 therapy might improve tumour responses to taxanes plus ramucirumab. Further, chemotherapy administered after anti-PD-1 therapy was manageable without unexpected toxicities, but immune-related adverse events during chemotherapy after anti-PD-1 therapy should be monitored carefully. Introduction Gastric cancer is the fifth most common type of cancer and the third leading cause of cancer-related death globally.1 Although some chemotherapy (CTx) regimens, including a platinum and fluoropyrimidine combination, trastuzumab (for human epidermal growth factor receptor 2 (HER2)-positive cases), taxanes with or without ramucirumab (RAM), irinotecan and trifluridine/tipiracil improve the survival outcomes of patients with advanced gastric cancer (AGC),2C7 its prognosis remains poor with a median survival of approximately 1?year. Therefore, further therapeutic development is needed for AGC. Immune checkpoint inhibitors demonstrate antitumour immune responses by activating effector T cells in various cancers. 8C12 In third-line or later-line treatments, two anti-programmed cell death 1 (PD-1) monoclonal antibodies (mAbs) have been approved for AGC based on the results of phase II and phase III trials:13 14 pembrolizumab by the US Food and Drug Administration for programmed death-ligand 1 (PD-L1)-positive tumours and nivolumab in Asian countries, irrespective of PD-L1 status. However, response rates with these anti-PD-1 mAbs are limited to 10%C15% in patients with AGC,13 necessitating more effective therapies to achieve tumour shrinkage. Prior PD-1 blockade enhances the antitumour effect of CTx in a melanoma mouse model.15 Indeed, anti-PD-1 therapy might improve responses to subsequent CTx without unexpected safety signals in patients with non-small cell lung cancer (NSCLC).16C19 Further, the phase III KEYNOTE-024 trial showed that patients with NSCLC treated with first\line pembrolizumab followed by cytotoxic CTx showed longer time to progression after initiation of second\line therapy than patients with first\line cytotoxic CTx followed by anti-PD\1 mAb.20 However, the effect of prior anti-PD-1 therapy on the efficacy and safety of CTx in patients with AGC remains unclear. Here, we assessed the tumour response to CTx and toxicities in patients with AGC, with or without prior exposure to anti-PD-1 therapy. Methods Patients Phenformin hydrochloride The effect of prior Mouse monoclonal to PGR anti-PD-1 therapy on the efficacy and safety of CTx in patients with AGC was evaluated retrospectively. We reviewed the medical records of consecutive patients with AGC who were treated with both CTx including taxanes plus RAM, taxanes monotherapy, or irinotecan, and anti-PD-1 therapy in the metastatic setting from June 2015 to April 2019 at the National Cancer Hospital East. Patients received 80?mg/m2 paclitaxel (PTX) or 100?mg/m2 nanoparticle albumin-bound PTX (days 1, 8 and 15) Phenformin hydrochloride with or without 8?mg/kg RAM (days 1 and 15) or 150?mg/m2 irinotecan, every 2 weeks before and after anti-PD-1 therapy. The doses of taxanes or irinotecan could be reduced at the investigators judgement. Patients who met the following criteria were included: (1) Presence of histologically proven gastric adenocarcinoma. (2) Underwent at least one administration with both CTx including taxanes plus RAM, taxanes monotherapy, or irinotecan, and anti-PD-1 therapy. (3) An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2. (4) Adequate bone marrow, hepatic and renal function. Patients were divided into two groups based on prior exposure to anti-PD-1 therapy: anti-PD-1-exposed and anti-PD-1-na?ve groups. Clinical outcomes after CTx were compared between anti-PD-1-exposed and anti-PD-1-na?ve groups in the overall population and in each CTx population. Assessment The study primarily aimed to investigate the efficacy and safety of CTx after prior anti-PD-1 therapy. We assessed the objective response rate.