Important to mention most modern oncology trials are incorporating ctDNA and pathologic response. Surrogates and biomarkers even RECIST aren’t perfect by any means but in real life they do correlate well with disease.
Agree. ctDNA has real potential, once appropriately validated. Unfortunately, regulators don’t accept it yet as primary endpoint, so there’s a long road ahead (MRD in myeloma took over a decade to validate). RECIST is a decent metric for estimating disease trends, if one has enough resources, stamina, and a little luck to run a large enough study to capture it. Somewhat like doing vascular surgery with kitchen knives. Technically possible, but that’s about the best you can say for it. Also RECIST-based endpoints generally don’t correlate well with OS, which is ultimately what matters most. And crossover doesn’t fully explain the lack of correlation https://ascopubs.org/doi/10.1200/JCO.2014.59.0489?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
Yes, studies like that make it challenging to determine how RECIST-based end points contribute to the overall survival of a cancer patient. An important nuance for the study you shared is that it was in the pre-immunotherapy era. Things have shifted pretty significantly in the last decade.
Absolutely. RECIST is even more irrelevant for immunotherapies as the majority of patients deriving clinical benefit live in the “stable disease” zone. Reason regulators have placed OS as the gold standard for immunotherapies and don’t accept RECIST based endpoints (expect in rare biomarker selected groups where the responses are deep, cross RECIST boundaries, and the tumor dynamics are visible to the human eye).
Important to mention most modern oncology trials are incorporating ctDNA and pathologic response. Surrogates and biomarkers even RECIST aren’t perfect by any means but in real life they do correlate well with disease.
Agree. ctDNA has real potential, once appropriately validated. Unfortunately, regulators don’t accept it yet as primary endpoint, so there’s a long road ahead (MRD in myeloma took over a decade to validate). RECIST is a decent metric for estimating disease trends, if one has enough resources, stamina, and a little luck to run a large enough study to capture it. Somewhat like doing vascular surgery with kitchen knives. Technically possible, but that’s about the best you can say for it. Also RECIST-based endpoints generally don’t correlate well with OS, which is ultimately what matters most. And crossover doesn’t fully explain the lack of correlation https://ascopubs.org/doi/10.1200/JCO.2014.59.0489?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
Yes, studies like that make it challenging to determine how RECIST-based end points contribute to the overall survival of a cancer patient. An important nuance for the study you shared is that it was in the pre-immunotherapy era. Things have shifted pretty significantly in the last decade.
Absolutely. RECIST is even more irrelevant for immunotherapies as the majority of patients deriving clinical benefit live in the “stable disease” zone. Reason regulators have placed OS as the gold standard for immunotherapies and don’t accept RECIST based endpoints (expect in rare biomarker selected groups where the responses are deep, cross RECIST boundaries, and the tumor dynamics are visible to the human eye).