Ashish M. Kamat, President of IBCG, Associated Editor at European Urology Oncology, shared Tom Powles‘s, Head of Solid Tumor Research at Barts Cancer Institute, reply on X, adding:
“Great points. B15 establishes the potency of EVP but we have to be careful not to conflate maximum systemic efficacy with total local clearance – they’re not the same thing, and the 55.8% pCR rate, impressive as it is, didn’t eliminate the need for the adjuvant tail to drive EFS and OS.
If a patient achieves cCR after 3-4 cycles, pushing to 9 without a surgical safety net is a significant gamble on the durability of that systemic response.
We know pCR plateaus – beyond a threshold we’re trading efficacy for toxicity – and cCR ≠ pCR regardless. 9 cycles as the defining threshold feels like a blunt instrument for a question that requires a scalpel (at least for now!).”
Quoting Tom Powles‘s reply:
“My feeling is that the relationship between response in the primary tumour and metastatic sites varies between pateints.
It will depend on the extent of MRD and the size of primary tumor.
The biology/heterogeneity will also have an important role. 4 cycles will probably be too few for some, while 9 will be too much for others. Using pCR or cCR to define duration of therapy maybe counterproductive (like using IMDC to pick ipi/nivo treatment in RCC). utDNA and ctDNA together maybe be better at this. Designing studies with utDNA and ctDNA is hard as it takes a while to get initial results, but it’s a useful exploratory endpoint.
I think we should do these studies too. EV209 asks is we can get the same results as in B15 if we do exactly the same thing except we don’t do surgery in some. It’s an interesting time as things change and I might not be right about this (e.g utDNA).”
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