I presented some exploratory analysis of biogene subgroups and potential associations with efficacy. So we looked at different markers such as rPFS and OS and overall response rate as well as PSA response and time to PSA progression. And just for short memory, the TALAPRO-2 study is a Phase III study that recruited patients that needed a treatment for first-line mCRPC...
I presented some exploratory analysis of biogene subgroups and potential associations with efficacy. So we looked at different markers such as rPFS and OS and overall response rate as well as PSA response and time to PSA progression. And just for short memory, the TALAPRO-2 study is a Phase III study that recruited patients that needed a treatment for first-line mCRPC. We started with recruiting patients that were in the all-comer population and those patients were prospectively tested for HRR alterations as well but once cohort one was fully recruited we started to recruit further patients with HRR alterations. So cohort two that was the cohort that I presented consists of patients that have HRR alterations within their tumor. Patients received either talazoparib plus enzalutamide or placebo plus enzalutamide. And the primary endpoint of the study was rPFS and OS and turned out positive. So that was previously presented at ASCO. And we were looking into the analysis or subgroup analysis of the biogenics and basically HRR was defined as having one of 12 alterations within the tumor tissue or the ctDNA and we used all data that we had from pre-screening and screening and decided to focus hands on six genes as 92% of the population had one of these or at least one of these six genes altered within their tumor or ctDNA. And we looked at rPFS and saw that for all six gene subgroups, which were ATM, CHK2, BRCA1, BRCA2, PALB2, and CDK12, patients had a benefit from the combination therapy. There was most pronounced for BRCA1, BRCA2, as expected, but also for CDK12 and PALB2, and not so much for CHK2 and ATM, but still beneficial or more beneficial than the monotherapy. We then looked at overall survival, which again, not surprisingly, was better for patients with BRCA1 and BRCA2 alterations, but also for CDK12. And it was a little bit surprising because for monotherapy, we know that patients did not have so much benefit from the PARP inhibitor therapy. And we assume that might be possible, or might be potentially because of the dual inhibition of the androgen receptor and PARP. And for the other endpoints, like overall response rate, five of six subgroups had a benefit from the combination therapy. And also for PSA progression and time to PSA, time to PSA progression and PSA response, all subgroups benefited from the combination. and that was something that probably not everybody had expected because a lot of people thought that those effects might be driven by BRCA1, BRCA2 only but the analysis showed that that was not the case.
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