ASCO 2020: 177Lu-PSMA more active than cabazitaxel in first analysis of randomized TheraP trial in mCRPC after docetaxel
Published on: May 31, 2020
Professor Michael Hofman presented the first results at the ASCO 2020 Virtual meeting from the randomized TheraP trial, comparing 177Lu-PSMA-617 with cabazitaxel in men with metastatic castration-resistant prostate cancer (mCRPC) after treatment with docetaxel. 177Lu-PSMA-617 was more effective than cabazitaxel, with fewer adverse events and PSA-PFS favoring 177Lu-PSMA-617.
The study randomized 200 men with mCRPC and the primary endpoint was PSA response rate, defined as a reduction of 50% or more from baseline. Secondary endpoints reported included PSA progression-free survival and adverse events. Patients were selected using both 68GaPSMA and 18F-FDG to exclude non-PSMA expressing disease.
With a median follow-up of 13.3 months, 66% (95% CI 56-75%) of patients treated with 177Lu-PSMA-617 achieved a 50% or better reduction in PSA, compared to 37% (95% CI 27-46%) with cabazitaxel (P<0.0001).
In addition, the risk of PSA progression or death was 31% lower favoring the 177Lu-PSMA-617 treatment arm. At the time of data cut-off, the data set was not yet mature for an overall survival analysis.
Safety outcomes also favored 177Lu-PSMA-617 with any grade 3-4 adverse event occurring in 35% compared to 54% with cabazitaxel. This was mostly driven by a lower risk of neutropenia and diarrhea with 177Lu-PSMA-617.
This is the first randomized controlled trial comparing 177Lu-PSMA-617 with a standard of care regimen in mCRPC after treatment failure with docetaxel. While the TheraP trial was not blinded, it has shown convincing activity of 177Lu-PSMA-617 in this disease setting with acceptable toxicity.
Further follow-up and survival outcomes are awaited as well as key secondary endpoints (radiologic PFS, quality of life). Also, results from the phase 3 VISION trial will help in ascertaining whether these benefits translate into a better overall survival.
In men with mCRPC and progressive disease after docetaxel 177Lu-PSMA-617 was more effective than cabazitaxel, with fewer adverse events and PSA-PFS favoring 177Lu-PSMA-617.