Phase II TheraP Trial Shows Promise for LuPSMA in mCRPC

Michael S. Hofman, FRACP, MBBS

Michael S. Hofman, FRACP, MBBS

Results from the TheraP 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 treatment with docetaxel, ¹⁷⁷Lu-PSMA-617 (LuPSMA) was more active than cabazitaxel (Jevtana).

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

“Lu-PSMA is a novel class of therapy with high activity and relatively low toxicity, consistent with the results of prior single-center studies in phase II data,” Michael S. Hofman, FRACP, MBBS, of the Peter MacCallum Cancer Center in Melbourne, Australia, said in a presentation. “Lu-PSMA appears to represent a favorable treatment option compared to cabazitaxel in a selected population with high PSMA-expression.”

The randomized phase II trial included men with mCRPC post docetaxel suitable for cabazitaxel, progressive disease with rising PSA and PSA ≥ 20 ng/mL, imaging with ⁶⁸Ga-PSMA-11 and ¹⁸F-FDG PET/CT that confirmed high PSMA-expression and no sites of FDG-positive/PSMA-negative disease, adequate renal, hematologic, and liver function, and those with ECOG performance status 0-2.

The study participants were randomized 1:1 to receive 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, AEs, and overall survival (OS). The data cutoff for the results reported at the meeting 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 LuPSMA vs 16 cabazitaxel).

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 im-proved 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.

Efficacy results were comparable 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.

“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.

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

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.

<<< 2020 ASCO Virtual Scientific Program