The Relevance of MFS as a Primary End Point in the ARAMIS Trial

Neal Shore, MD, FACS, discusses the use of metastases-free survival as the primary end point in the ARAMIS trial, which looked at darolutamide in men with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC).

Neal Shore, MD, FACS, the US chief medical officer of surgery and oncology at GenesisCare USA and the director and certified principal investigator at the Carolina Urologic Research Center, discusses the use of metastases-free survival (MFS) as the primary end point in the ARAMIS trial (NCT02200614), which looked at darolutamide (Nubeqa) in men with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC).

According to Shore, MFS is a composite end point that has largly been driven by radiographic progression. Radiographic progression is where most events occurs. MFS was found to correlate overall survival in a castration sensitive population in the ICECaP trial (NCT03673787), which looked at ipatasertib in combination with atezolizumab (Tecentriq).

The FDA has also recognized MFS as a pathway for approval, according to shore. The ARAMIS trial found that the study agent caused nearly a 2-year delay in MFS, with 80% of events being radiographic progression. The secondary end point of overall survival was also met, according to Shore. 

0:08 | MFS is a somewhat of a composite end point that has largely been driven by studies to look at both radiographic progression, and that's really where most of the events occur, but then also death or survival. really wonderful work by Christopher Sweeney, MBBS and others in the ICECaP analysis demonstrated in a meta-analysis that MFS correlated very well also with overall survival in the castration sensitive population. I think to the credit of the FDA, they recognize that MFS is now a pathway for approvability for drug indications. And in ARAMIS, we certainly in a very statistically significant way, demonstrated the benefit of metastasis free survival for nmCRPC patients. A near 2-year delay improvement in MFS, largely driven by 80% of the events were radiographic progression. But the subsequent secondary end point of overall survival was also robustly demonstrated. So, I think this is a really great example of strategic trial development, in collaboration with FDA recognizing the importance of approvable pathways beyond just overall survival. And fortunately, overall survival was also subsequently demonstrated.