mCRPC in focus
Transcript: Differences in clinical trial design for PARP inhibitors and novel hormonal therapies
Dr Neeraj Agarwal
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There were three trials which happened in the first line mCRPC space using PARP inhibitors. First one is the MAGNITUDE trial with abiraterone plus niraparib combination.
Second is PROpel trial with abiraterone plus olaparib combination. And third trial is the TALAPRO-2 trial, which is testing the combination of enzalutamide plus talazoparib plus enzalutamide. All these trials are inherently different with different patient population, but there are similarities and dissimilarities.
Similarity stops at the type of combination being used and the control arm and the first line mCRPC setting. Although many patients in different trials have been exposed to NHTs or chemotherapy with docetaxel or abiraterone. But I think one of the major dissimilarities was in the MAGNITUDE trial, it was prospective tissue testing requirement before patient could enrol on the MAGNITUDE trial with abiraterone plus olaparib and in the TALAPRO-2 trial.
Prospective tissue testing was required. In the PROpel trial, all-comer patient population were enrolled, and then investigators went back and looked at who got tested, who had positivity or negativity for HRR mutations based on retrospective testing. Second major difference, MAGNITUDE trial had predefined cohorts of HRR positive patients and HRR negative patients. There were essentially two different trials happening under the umbrella of MAGNITUDE trial. PROpel trial was one trial, including all-comer populations and then went back and saw who had HRR positivity and who had HRR negativity. TALAPRO-2 trial, somewhere is in the middle. It had an all comer population, all prospectively tested.
HRR mutation positivity was used as a stratification factor, which basically put this at par with almost, almost at par with the MAGNITUDE trial as far as having two different trials within one trial is concerned. But then TALAPRO-2 trial had a separate cohort too, which was only focused on enrolling HRR positive patients. And these data were presented by Dr. Karim Fizazi in the ASCO 2023 meeting. So those were the major differences in their design and the methodology of these phase 3 trials of PARP inhibitor combination in the first line mCRPC setting.
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