Phase II Trial Finds LuPSMA May be Effective for Men with mCRPC

A randomized phase II trial presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program found that in men with metastatic castration resistant prostate cancer (mCRPC) who progressed after being treated with docetaxel, ¹⁷⁷Lu-PSMA-617 (LuPSMA) was more active than cabazitaxel (Jevtana).

Even further, grade 3 to 4 adverse events (AEs) were relatively fewer with the use of LuPSMA and PSA-progression-free survival (PSA-PFS) favored LuPSMA as well. 

“(Metastatic castration resistant prostate cancer) is a lethal disease, and novel treatments are urgently needed to improve patient outcomes,” Michael S. Hofman, FRACP, MBBS, of the Peter MacCallum Cancer Center in Melbourne, Australia, said in a presentation of the results. 

The trial, titled TheraP, randomly assigned men with mCRPC, and imaging with ⁶⁸Ga-PSMA-11 and ¹⁸F-FDG PET/CT that confirmed high PSMA-expression and no sites of FDG-positive/PSMA-negative disease, in a 1:1 fashion to either LuPSMA or cabazitaxel. Men in the experimental arm of the study underwent post therapy SPECT/CT after each cycle of LuPSMA, and if an exceptional response was demonstrated, their treatment was paused and could resume thereafter at the time of PSA progression. 

The primary end point of the study was PSA response rate, defined by ≥50% reduction. Key secondary efficacy endpoints included PSA-PFS, adverse events, and overall survival (OS). The data cutoff for the results reported was March 31, 2020. 

Overall, 200 of 291 men across 11 in sites in Australia who were PET screened were randomized to LuPSMA (n = 99) or cabazitaxel (n = 101). Importantly, 17 patients withdrew or died before receiving study treatment (1 in the LuPSMA arm vs 16 in the cabazitaxel arm). 

The PSA response rate was higher in patients who received LuPSMA than those who received cabazitaxel (66% [95% CI, 56-75] vs 37% [95% CI, 27-46]; P < 0.001). This represented a 29% (95% CI, 16%-42%; P < 0.0001) absolute greater PSA response rate in participants receiving LuPSMA compared to cabazitaxel. For sensitivity analysis per protocol, the difference observed was 23% (95% CI, 9%-37%; P = 0.0016). 

At a median follow-up of 13.3 months, LuPSMA was shown to have significantly improved PSA-PFS (HR, 0.69; 95% CI, 0.50-0.95; P = 0.02). This data was based on 157 of the 170 events required for primary analysis.

“Importantly, improvements in overall survival have not yet been demonstrated, and we eagerly await the results of the upcoming phase III VISION trial,” Hofman said.

Efficacy results were similar when the analyses were restricted to per-protocol treated men. 

Grade 3 to 4 AEs occurred in 36% of men treated with LuPSMA compared with 49% of men treated with cabazitaxel. Moreover, grade 5 AEs occurred in 11 patients treated with LuPSMA and 5 patients treated with cabazitaxel. There were no treatment-related deaths. 

The investigators indicated that they await further follow-up results of other key secondary endpoints, including radiologic PFS (the next planned analysis after 170 events), quality of life, and PFS. Moreover, they believe that LuPSMA warrants study in earlier phases of prostate cancer, as well as in combination with other therapies.

“On the basis of these results, LuPSMA appears to represent a new class of effective therapy for men with metastatic castration-resistant prostate cancer,” said Hofman. 

Reference:

Hofman MS, Emmett L, Sandhu SK, et al. TheraP: A randomized phase II trial of 177Lu-PSMA-617 (LuPSMA) theranostic versus cabazitaxel in metastatic castration resistant prostate cancer (mCRPC) progressing after docetaxel: initial results (ANZUP protocol 1603). Presented at: 2020 ASCO Virtual Scientific Program; May 29, 2020. Abstract 5500.