Anti-PD-1 antibody plus regorafenib in refractory microsatellite stable metastatic colorectal cancer: A retrospective study

ABSTRACT

Background: To investigate the efficacy and safety of anti-PD-1 antibody plus regorafenib in refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Methods: We retrospectively analyzed the efficacy and safety of 103 MSS mCRC patients treated with anti -PD-1 antibodies(including nivolumab, pembrolizumab, camrelizumab, sintilimab, and toripalimab) combined with regorafenib(80 mg once daily for 21 days on/7 days off)between July 2019 and June 2021 in Hunan Cancer Hospital. Results: 103 patients had received at least one dose of regorafenib plus anti -PD-1 antibody. Due to COVID-19 pandemics, economic or other reasons, 48 patients (46.6%) did not return to hospital for second cycle of combination treatment .With a median follow-up of 5.30 months (range 0.50-22.50), the median overall survival (mOS) and progression-free survival (mPFS) were 8.40 months (95%CI6.40-12.70) and 2.50 months (95%CI2.27-3.47) in the entire cohort, respectively. The mOS and mPFS were significantly longer in patients who received more than 1 cycle (n = 55, 53.4%) compared to those who received just 1 cycle(n = 48, 46.6%). (16.07 vs. 4.37 months, HR 0.21;95%CI[0.12-0.38];P<0.001;3.10 vs. 1.11 months, HR 0.12;95%CI [0.05-0.31];P<0.001). Further analyses revealed that sintilimab (n = 66, 64.1%) significantly improved mPFS from 1.61 months to 3.30 months, compared to other anti-PD-1 antibodies (n = 37, 35.9%) (HR 0.55;95%CI[0.31-0.99];P = 0.044). Cox multivariate regression analysis demonstrated that cycles of regorafenib plus PD-1 was a significant independent risk factor for the OS and PFS(P0.001).Patients who had previously undergone surgery were better than those who had not (P= 0.029).Sintilimab plus regorafenib had a better PFS benefit(P= 0.044.)Seven patients were diagnosed as partial response and another 16 cases were diagnosed as stable disease in the 55 patients who were evaluated, but no complete response. Thus the objective response rate was 12.7% and the disease control rate was 41.8%.Treatment-related adverse events of grade 3 or higher occurred in 13 (12.6%) patients. Conclusions: The combination of regorafenib plus anti-PD-1 antibody had a manageable safety profile and promising efficacy in MSS mCRC patients, especially in patients who received more than one cycle. Compared with the other anti-PD-1 antibodies, sintilimab may have more encouraging efficacy, which needs further prospective studies.