Abstract 5531: PD-1 blockades plus targeted therapy and cytotoxic drugs as conversion therapy in unresectable metastatic colorectal cancer (mCRC): A real-world experience

Abstract Background: Resection of metastatic tumor site has been proven beneficial for survival in mCRC, thus the need for conversion therapy of mCRC is strong. Anti-PD-1 antibody has presented durable clinical response in mismatch repair deficient (dMMR)/microsatellite instable (MSI-H) mCRC as first-line treatment while its efficacy in microsatellite stable (MSS) mCRC is still controversial. Combination of anti-PD-1 and targeted therapy or chemotherapies was regarded as potential regimens in MSS mCRC. Moreover, it is fully elucidated that immune checkpoint inhibitor used in initial therapy would have higher probability to achieve treatment response. We retrospectively analyzed the efficacy of anti-PD-1 plus targeted drugs and cytotoxic drugs as conversion/first-line therapy in fifteen untreated mCRC. Methods: Thirteen MSS and two MSI-H mCRC were included. All patients received at least one cycle of anti-PD-1 (Pembrolizumab, Sintilimab or Toripalimab, q3w) combined with bevacizumab or cetuximab plus chemotherapy (FOLFOX or FOLFOXIRI regimens). Results: 8 patients were RAS-mutant and 1 patient harbored BRAF-V600E. 13 patients had liver metastasis, 3 had lung metastasis and 3 had retroperitoneal lymph metastasis. 4 patients, including 2 MSI-H patients and 2 MSS patients had complete response (CR), 8 patients had partial response (PR), 2 patients had stable disease (SD) and 1 patient had progression disease (PD). The conversion rate was 80% (12/15), including 10 patients received resection or thermal ablation of metastatic tumor and 2 patients achieved CR. 9 patients were R0 resection and 10 patients achieved NED (no evidence of disease) status. G3-4 treatment-related adverse events (AEs) occurred in 1 patient (neutropenia, n=1). No patient discontinued treatment due to adverse events. Conclusions: The triplet regimen of anti-PD-1, bevacizumab or cetuximab and chemotherapy was safe and tolerant and showed encouraging anti-tumor activities in MSS mCRC. Our experience suggested the clinical value of PD-1 blockades as initial treatment in MSS mCRC. Citation Format: Ling Huang, Liying Zhao, Xinyi Liu, Mengli Huang. PD-1 blockades plus targeted therapy and cytotoxic drugs as conversion therapy in unresectable metastatic colorectal cancer (mCRC): A real-world experience [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5531.