ASCO GI 2022 | Prior RT may potentially enhance treatment of MSS-CRC with regorafenib and pembrolizumab

Afsaneh Barzi, MD, PhD, City of Hope, Duarte, CA, outlines the results of the Phase I/II trial (NCT03657641) that investigated the use of regorafenib and pembrolizumab for the treatment of patients with refractory microsatellite-stable colorectal cancer (MSS-CRC). The aim of Phase I of the study was to uncover the optimal dose of regorafenib to use in combination with 200mg of pembrolizumab administered every 3 weeks. Phase II investigated progression-free survival (PFS). The recommended dose of regorafenib was found to be 80mg administered every day on days 1 to 14 in a 21-day cycle. A total of 73 patients met the eligibility criteria for Phase II, 70 of which were treated at the 80mg recommended dose. 23% of patients had rectal cancer and 77% had colon cancer and 67% of the study population had been heavily pretreated. The trial did not meet the prespecified PFS threshold, however, compelling results were found in the subgroup analysis. A univariate analysis showed that patients with no liver metastasis had better PFS, as well as patients who had undergone surgery for metastases. Notably, patients who had previously received radiotherapy (RT) had significantly improved PFS. In a multivariate analysis, the only significant variable in terms of PFS was prior RT. Prior RT as a potential sensitizer to immunotherapy has previously been reported in a population of patients with non-small cell lung cancer (NSCLC), suggesting prior RT to be a predictor for patients with NSCLC who will benefit from treatment with pembrolizumab. This Phase I/II trial revealed novel findings in patients with gastrointestinal malignancies that prior treatment with radiotherapy may enhance the effect of combining regorafenib with pembrolizumab. This interview took place at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2022.