177Lu-PSMA-617, an investigational radioligand therapy, showed stronger clinical activity than cabazitaxel in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel.
The investigational radioligand therapy 177Lu-PSMA-617 (LuPSMA) was more clinically active than cabazitaxel (Jevtana) in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed after docetaxel, according to findings from the phase 2 TheraP trial presented during the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.
The PSA response rate was 66% (95% CI, 56-75) for patients receiving LuPSMA compared with 37% (95% CI, 27-46) for those treated with cabazitaxel, representing a 29% absolute greater PSA response rate (95% CI, 16-42; P <.0001). For sensitivity analysis per protocol, the difference observed was 23% (95% CI, 9-37; P = .0016). PSA-progression-free survival (PSA-PFS) also LuPSMA, as did the safety profile, with relatively fewer grade 3 to 4 adverse events (AEs) reported for the radioligand therapy.
“(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 when presenting the results. “On the basis of these results, LuPSMA appears to represent a new class of effective therapy for men with metastatic castration-resistant prostate cancer.”
The phase 2 TheraP trial results included 200 patients with mCRPC who had undergone imaging with 68Ga-PSMA-11 and 18F-FDG PET/CT confirming high PSMA-expression and no sites of FDG-positive/PSMA-negative disease. Patients were treated at 11 clinical locations in Australia.
Patients were randomized in a 1:1 ratio to LuPSMA (n = 99) or cabazitaxel (n = 101). In the LuPSMA cohort, men received posttreatment SPECT/CT after each cycle, with those achieving an exceptional response having their treatment paused. Treatment would subsequently resume at the time of PSA progression.
PSA response rate was the primary study end point. A response was defined as ≥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.
PSA-PFS was significantly improved in the LuPSMA arm compared to the cabazitaxel arm at a median follow-up of 13.3 months (HR, 0.69; 95% CI, 0.50-0.95; P = .02). These results were based on 157 of the 170 events required for primary analysis.
Regarding safety, grade 3/4 AEs occurred in 36% of the LuPSMA cohort compared with 49% of the cabazitaxel arm. Grade 5 AEs occurred in 11 patients who received LuPSMA compared with 5 patients treated with cabazitaxel; however, there were no treatment-related deaths.
The researchers are now awaiting data for additional secondary end points, including radiologic PFS (the next planned analysis after 170 events), quality of life, and PFS.
Hofman also noted that, “Importantly, improvements in overall survival have not yet been demonstrated, and we eagerly await the results of the upcoming phase 3 VISION trial.”
The open-label phase 3 VISION trial, (NCT03511664) accrued patients with progressive PSMA-positive mCRPC who received at least 1 novel androgen axis drug (eg, enzalutamide [Xtandi] or abiraterone acetate [Zytiga]) and were previously treated with 1 to 2 taxane regimens. Patients were randomized to 177Lu-PSMA-617 plus best supportive/best standard of care or best supportive/best standard of care alone.
The primary outcome measure for the VISION trial is overall survival. Secondary end points include radiographic PFS, response (RECIST criteria), time to first symptomatic skeletal event, safety and tolerability, health-related quality of life, and biochemical response as measured by PSA.
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.