Dr. Kim on Efficacy and Next Steps With Regorafenib/Nivolumab Combo in CRC

Richard D. Kim, MD, a medical oncologist within the Department of Gastrointestinal Oncology at Moffitt Cancer Center and an assistant professor of oncology with University of South Florida College of Medicine, discusses the efficacy of and next steps for a phase 1/1b study with regorafenib (Stivarga) and nivolumab (Opdivo) in patients with mismatch repair proficient advanced refractory colorectal cancer (CRC).

The phase 1b study treated a small population of 28 patients with the doublet regimen, including 12 patients in the phase 1 portion and 16 patients in the expanded cohort. The median progression-free survival was 4.3 months (95% CI, 2.1-15.6) and the median overall survival was 11 months (95% CI, 5.9–not reached) after a median follow-up of 4.7 months, says Kim. The toxicity seen in the study was very similar to what was has been seen in the group phase 1b REGONIVO study, which was based in Japan. The most common adverse effects associated with the combination across all grades were rash (39.3%), fatigue (39.3%), palmar-plantar erythrodysesthesia syndrome (35.7%), and some gastrointestinal toxicity. The study aims to enroll a total of 40 patients to the expanded cohort within the next 2 to 3 months for a total data set of 52 patients. Those data will be presented sometime in 2021, adds Kim.

The findings from this study were quite different than the REGONIVO study for a number of reasons. One possibility is that the baseline demographic could be slightly different. Many patients included in the study had a KRAS mutation (71.4%) while even more were found to have right-sided tumors (85.7%). There were also many patients with liver (67.9%) versus lung metastases (60.7%). Investigators hypothesize that patients with lung metastases do better because they seem to be more immunogenic than patients with liver metastases. This is difficult to confirm, as the study numbers are small; however, mixed responses have been seen between patients with liver and lung metastases, explains Kim. This theory stems from patients with lung lesions having experienced tumor shrinkage, while those with liver lesions had disease progression on the combination regimen. However, more data are needed to confirm this.

Unlike the data from the REGONIVO study, Kim explains that the combination regimen shows very modest efficacy with expected safety data. However, the investigators are waiting to accrue a cohort of 40 patients in the expanded cohort to gather more efficacy data and help identify biomarkers or phenotypes of the tumor that are predictive of the response to regorafenib and nivolumab, concludes Kim.