PD-1 blockade combined chemotherapy and bevacizumab in DNA mismatch repair-proficient/microsatellite stable colorectal liver metastases.

Abstract

e15547 Background: Although PD-1 blockade has been recommended as the first line treatment in DNA mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC), it is worthwhile to investigate whether mCRC with DNA mismatch repair-proficient/microsatellite stable(pMMR/MSS) tumors benefit from a combination treatment with PD-1 blockade. Methods: In this cohort, ten patients with pMMR/MSS colorectal liver metastases (CRLM) treated in the 6th Affiliated Hospital of Sun Yat-sen University were enrolled. All the patients were exploratively treated with at least four doses of PD-1 monoclonal antibody combined with chemotherapy and bevacizumab as neoadjuvant/adjuvant therapy. The aim of the study was to evaluate the short-term efficacy and safety of this combined strategy. Results: All the 10 patients were confirmed pMMR/MSS by IHC or next generation sequencing (NGS). Eight of the 10 patients accepted the combined therapies before primary tumor resections, disease control rate (DCR) was 100% (8/8) and objective response rate (ORR) was 62.5% (5/8). The ORR of liver metastases was 70% (7/10) after this treatment. Pathologic complete response (pCR) was achieved in one patient’s primary tumor and was also achieved in another patient’s hepatic lesion. Four patients underwent simultaneous resection of primary tumor and liver metastases. Nine patients underwent microwave ablation for liver metastases. Five patients were assessed no evidence of disease (NED) with a median progress-free survival (PFS) of 5.0 (4.2-9.9) months after multimodality treatments for both primary and metastatic lesions. No immunotherapeutic associated sever adverse event (SAE) or operational complications were found in this cohort. Conclusions: PD-1 blockade combined chemotherapy and bevacizumab was safe and effective for patients with pMMR/MSS CRLM, which might lead to better tumor regression as well as more chances of NED. Further clinical phase II studies of evaluation of long-term efficacy of this combined strategy was needed.