Treatment with 177lutetium-PSMA-617 (LuPSMA; Pluvicto®) is associated with similar overall survival (OS) but less toxicity than cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC) that progresses after docetaxel therapy, according to updated findings from the TheraP trial presented at the 2022 ASCO Annual Meeting.1

In patients with mCRPC for whom cabazitaxel is considered the next treatment option, LuPSMA is a suitable alternative, with lower toxicity and better patient quality of life, principal investigator Michael S. Hofman, MBBS, of the Peter MacCallum Cancer Centre in Victoria, Australia, said in an interview.

The US Food and Drug Administration on March 23 approved LuPSMA for the treatment of mCRPC following treatment with androgen receptor pathway inhibition and taxane-based chemotherapy. The drug is marketed as Pluvicto® by Advanced Accelerator Applications, a Novartis company.

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In 2021, Dr Hofman’s group reported in The Lancet that, in patients with mCRPC progressing after docetaxel, those treated with LuPSMA had a significant 38% decreased risk for progression (95% CI, 0.45-0.85; P =.0028), a significantly better PSA response rate (66% vs 37%), RECIST response rate (49% vs 24%), fewer grade 3-4 toxicities (33% vs 53%), and better patient-reported outcomes when compared to cabazitaxel.2 Cabazitaxel was the only standard life-prolonging therapy otherwise available to these patients, they noted.

At ASCO 2022, Dr Hofman reported the secondary endpoint of OS with mature follow-up data and presented results from patients excluded from the trial because of low PSMA expression or discordant disease on imaging with PSMA-PET and FDG-PET.

For the TheraP trial (NCT03392428), investigators randomly assigned 99 men to receive LuPSMA and 101 to receive cabazitaxel. Of the 291 patients who registered for the trial, 80 (28%) who registered after initial eligibility were excluded after PSMA-PET or FDG-PET.

Follow-up information was available for 61 patients (76%). After a median follow-up of 36 months (with data cutoff on December 31, 2021), 70 of the 101 cabazitaxel-treated patients and 77 of the 99 LuPSMA recipients died, as did 55 of 61 patients excluded after PSMA-PET or FDG-PET.

The longer follow-up showed that the OS rate was similar for the LuPSMA and cabazitaxel groups (restricted mean survival time [RMST] to 36 months was 19.1 and 19.6 months, respectively; 95% CI, −3.7 to 2.7).

The longer follow-up revealed no new safety issues, according to the investigators. Dr Hofman pointed out that 14 of the patients randomized to cabazitaxel withdrew before receiving treatment, and most received LuPSMA off trial; these patients were analyzed for efficacy as if they had received cabazitaxel.

Median survival was considerably shorter for patients excluded on imaging with PSMA-PET and FDG-PET prior to randomization due to either low PSMA expression or FDG-discordant disease. Among the 61 patients in this group, RMST to 36 months was 11.0 months (95% CI, 9.0-13.1) following treatment that included cabazitaxel in 29 (48%) and LuPSMA in 3 (5%). In comparison, the RMST to 36 months for the randomized patients was 18.8 months. 

“In conclusion,” Dr Hofman told attendees, “the TheraP data supports the choice of 177lutetium-PSMA-617 over cabazitaxel for patients with PSMA-positive progressive mCRPC after docetaxel and androgen receptor pathway inhibitors on the basis of its higher PSA response, greater PFS benefit, quality of life benefits, favorable safety profile [and] dosing schedule — 6 weeks vs 3 weeks — and similar survival outcomes to cabazitaxel, a proven life-prolonging therapy.”

In a separate analysis of ANZUP 1603 presented at the 2022 Genitourinary Cancers Symposium in February, Dr Hofman and colleagues reported that high uptake of PSMA on PSMA-PET predicted a greater likelihood of favorable response to LuPSMA compared with cabazitaxel, whereas a high volume disease on FDG-PET was associated with a worse prognosis regardless of which treatment patients received.3

Disclosures: TheraP was sponsored by the ANZUP Cancer Trials Group and supported by the Prostate Cancer Foundation Australia, ANSTO, Advanced Accelerator Applications (a Novartis company), Movember, and the NHMRC Clinical Trials Centre at the University of Sydney. 


1. Hofman MS, Emmett L, Sandhu S, et al. TheraP: 177Lu-PSMA-617 (LuPSMA) versus cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel — overall survival after median follow-up of 3 years (ANZUP 1603). Presented at ASCO 2022; June 3-7, 2022. Abstract 5000.

2. Hofman MS, Emmett L, Sandhu S, et al. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021;397(10276):797-804. doi:10.1016/S0140-6736(21)00237-3

3. Buteau JP, Martin AJ, Emmett L, et al. PSMA PET and FDG PET as predictors of response and prognosis in a randomized phase 2 trial of 177Lu-PSMA-617 (LuPSMA) versus cabazitaxel in metastatic, castration-resistant prostate cancer (mCRPC) progressing after docetaxel. (TheraP ANZUP 1603). Presented at 2022 Genitourinary Cancers Symposium; February 17-19, 2022. Abstract 10.