ASCO 2020: 177Lu-PSMA more active than cabazitaxel in first analysis of randomized TheraP trial in mCRPC after docetaxel

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.