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Does Physical Activity Play a Role in the Efficacy of RegoNivo for MSS-mCRC?
1Patient Knowhow, Inc., San Mateo, CA.
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.
Insights
The combination of Regorafenib and Nivolumab (RegoNivo) showed promising results in Japanese patients with MSS-mCRC. Subsequent trials in North America did not replicate these outcomes, possibly due to differences in patient ECOG Performance Status (PS).
Area of Science:
- Oncology
- Clinical Trials
- Biomarkers
Background:
- Initial studies of Regorafenib and Nivolumab (RegoNivo) in Japanese patients with chemo-refractory MSS-mCRC demonstrated a 33% response rate.
- Subsequent North American trials failed to replicate these positive outcomes.
- Hypotheses for the discrepancy include a higher proportion of liver metastases in North American trials or differences in patient performance status.
Purpose of the Study:
- To re-examine clinical trial data for RegoNivo in MSS-mCRC.
- To compare outcomes between the original Japanese trial and subsequent North American trials.
- To investigate the role of ECOG Performance Status (PS) as a potential factor influencing treatment response.
Main Methods:
- Retrospective analysis of available trial data for RegoNivo in MSS-mCRC.
- Comparison of patient characteristics, specifically ECOG PS and liver metastases, between Japanese and North American trials.
Main Results:
- The original Japanese trial exclusively included patients with ECOG PS = 0.
- Subsequent North American trials predominantly included patients with ECOG PS = 1.
- Differences in the percentage of patients with liver metastases were less pronounced than differences in ECOG PS.
Conclusions:
- ECOG Performance Status (PS) may serve as a composite marker for patient fitness and disease biology.
- Poor ECOG PS might indicate unfavorable tumor biology, potentially leading to rapid progression before RegoNivo can be effective.
- Further investigation is warranted to explore the relationship between ECOG PS, physical activity, and response to RegoNivo in MSS-mCRC.
