Marwan G. Fakih, MD, Discusses Regorafenib Plus Nivolumab in CRC and Multidisciplinary Care


CancerNetwork® sat down with Marwan G. Fakih, MD, of City of Hope at the 2021 ASCO Annual Meeting to talk about a potential multidisciplinary treatment approach to colorectal cancer with regorafenib/nivolumab.

At the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork® spoke with Marwan G. Fakih, MD, about how patients with colorectal cancer (CRC) may benefit from a multidisciplinary approach to care utilizing the combination of regorafenib (Stivarga) and nivolumab (Opdivo). A phase 2 clinical trial (NCT04126733) was conducted in North America to assess safety in this population with the immune-oncology combination. Notably, a similar phase 1b REGONIVO/EPOC1603 study (NCT03406871) had taken place previously in Japan in patients with advance CRC or gastric cancer. Although the study did not demonstrated the same outcomes as were seen in Japan, an absence of liver metastases may warrant further investigation.


There is always a multidisciplinary approach [to care] for our patients. This study brings up a lot of questions: What happens if somebody has liver metastases? Could [we] resect liver metastases? Could combinations of nivolumab plus regorafenib in the future be helpful for patients with liver and extrahepatic disease who have limited volume extrahepatic disease where [the liver has been resected] surgically? Should you take those patients for a liver resection? All of these are important questions that should be considered in the future.

The regorafenib/nivolumab study that was conducted in the US is a step forward. The questions that arise from this study, and many other studies, have to be answered prospectively in a clinical research setting. There are more questions today than there are answers. But the importance of the regorafenib/nivolumab trial that we presented at ASCO, as well as the phase 2 LEAP trial (NCT03797326) and other studies that have looked at PD-1 plus tyrosine kinase inhibitors, is that it tells us that the concept of mismatch repair (MMR)–proficient CRC being an immune-resistant disease is not true. MMR-proficient CRC can respond to immunotherapy.

The question is now, what is the best combination? Who are the best patients? What biomarkers do we use and select for patients [potentially undergoing] immunotherapy? What should be the subsequent clinical trial questions that we should be answering? There are many of those, and even today, there are phase 3 trials that are being investigated in this area. We will have more answers moving forward. I still think the combination should still be considered investigational at this point. We should move forward with additional studies in this area.


1. Fakih M, Pratap K, Raghav S, et al. Single-arm, phase 2 study of regorafenib plus nivolumab in patients with mismatch repair-proficent (pMMR)/microsatellite stable (MSS) colorectal cancer (CRC). J Clin Oncol. 2021;39(suppl 15):3560. doi:10.1200/JCO.2021.39.15_suppl.3560

2. Fukuoka S, Hara H, Takahasi N, et al. Regorafenib plus nivolumab in patients with advanced gastric or colorectal cancer: an ppen-label, dose-escalation, and dose-expansion phase Ib Trial (REGONIVO, EPOC1603). 2020;38(18):2053-2061. doi:10.1200/JCO.19.03296

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