Does Physical Activity Play a Role in the Efficacy of RegoNivo for MSS-mCRC?

Abstract

Background: In 2019, researchers reported a remarkable 33% response rate and a median progression free survival of almost 8 months in a study of Regorafenib and Nivolumab (RegoNivo) with 24 Japanese patients with chemo-refractory MSS-mCRC. These clinical outcomes were subsequently not replicated in clinical trials in North America. One hypothesis that has been put forth is that trials in North America had a higher percentage of patients with liver metastases who are less likely to respond to Regorafenib and Nivolumab. We propose an alternate hypothesis reflected by ECOG Performance Status = 0.

Methods: We reexamined the available trial data on RegoNivo for MSS-mCRC in the original Japanese trial and compared it to subsequent clinical trials of the same combination and setting in North America.

Results: 100% of patients on the original Japanese trial were ECOG PS = 0 whereas those in the subsequent trials in North America included a majority of patients with ECOG PS = 1. The percentage of patients with liver metastases is not as clearly different among these trials compared to ECOG PS 0.

Conclusions: ECOG PS may represent a composite marker of patient physical activity and/or fitness and disease biology. Although ECOG PS and physical activity are not completely the same, ECOG PS and physical activity of patients has not been fully investigated in the context of response to RegoNivo. Alternatively, it is possible that poor ECOG PS may also reflect unfavorable tumor biology, and such tumors might progress before RegoNivo has a chance to provide clinical benefit.

Keywords: ECOG; Immunotherapy; Microsatellite stable; Nivolumab colorectal cancer; Physical activity; Regorafenib.