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Regorafenib, ipilimumab and nivolumab activity in microsatellite stable colorectal cancer patients with disease progression and prior chemotherapy
An immunotherapy combination of regorafenib, ipilimumab and nivolumab demonstrated interesting clinical activity in microsatellite stable metastatic colorectal cancer patients, as shown in a new study published on JAMA Oncology.
This single-center, nonrandomized clinical trial enrolled 39 patients with microsatellite stable colorectal cancer whose disease progressed after standard chemotherapy and who had not received prior regorafenib or anti–PD-1 therapy, with the aim to determine the recommended phase 2 dose of an immunotherapy combination of regorafenib, ipilimumab and nivolumab. Patients received regorafenib daily for 21 days every 4 weeks; fixed-dose ipilimumab, 1 mg/kg, intravenously every 6 weeks; and fixed-dose nivolumab, 240 mg intravenously every 2 weeks. No dose-limiting toxic effects were noted in the first 9 patients at the starting dose of regorafenib, ipilimumab and nivolumab; with regorafenib 80 mg daily no dose de-escalation was needed and this dose was declared the recommended phase 2 dose. With this dose, the combination had a manageable safety profile and an overall response rate of 27.6%, a median progression-free survival of 4 months, and a median overall survival of 20 months. Responses were limited to patients without liver metastases (overall response rate, 36.4%). «This study lends further support to the significance of metastatic disease site in dictating responses to immunotherapy», authors say. «Consistent with our prior reports, results suggest that liver metastatic disease is a strong biomarker of resistance to immunotherapy in patients with microsatellite stable colorectal cancer. Four of the 8 responding patients had lung-only metastatic disease, suggesting that this group may have the most favorable tumor microenvironment to predispose them to respond to therapy. This nonrandomized clinical trial shows that a combination of regorafenib, 80 mg/day, ipilimumab, 1 mg/kg every 6 weeks, and nivolumab, 240 mg every 2 weeks, has encouraging activity in patients with non-liver metastatic microsatellite stable colorectal cancer: additional investigations will be needed to confirm the value of each of these components and to further define additional clinical and molecular biomarkers of response», authors conclude.