Adding the targeted radioligand therapy 177Lu-PSMA-617 (LuPSMA) to best standard of care (BSC) improved overall survival (OS) in patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC), according to findings from the phase 3 VISION trial.1
LuPSMA also extended progression-free survival (PFS) when added to BSC versus BSC alone. No new safety signals emerged in the trial. Data from the study will be presented at a future scientific conference, according to Novartis, the developer of LuPSMA.
“Patients with metastatic castration-resistant prostate cancer have a less than 1 in 6 chance of surviving 5 years and need new treatment options. These groundbreaking data confirm our belief in the potential of 177Lu-PSMA-617 to reimagine outcomes for these patients through phenotypic precision medicine. We intend to submit these data to regulatory authorities as soon as possible,” John Tsai, head of Global Drug Development and chief medical officer for Novartis, stated in a press release.
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 LuPSMA plus BSC or BSC alone. The coprimary end points of the trial were OS and PFS.
Findings from the phase 2 TheraP trial of LuPSMA were previously published in the Lancet.2 The results showed that LuPSMA had stronger clinical activity with fewer grade 3/4 adverse events (AEs) compared with cabazitaxel (Jevtana) in patients with mCRPC.
The results, which were initially shared during the 2020 American Society of Clinical Oncology Virtual Scientific Program,3 showed a PSA response rate of 66% with LuPSMA compared with 37% with cabazitaxel, representing a 29% absolute greater PSA response rate (P <.0001). For sensitivity analysis per protocol, the difference observed was 23% (P = .0016).
Regarding safety, grade 3/4 AEs occurred in 33% versus 53% of the LuPSMA versus cabazitaxel arms, respectively. There were no LuPSMA-related deaths.
The TheraP trial enrolled 200 patients with mCRPC who progressed after docetaxel. Patients 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. Over 90% of patients in each arm had received abiraterone acetate, enzalutamide, or both.
Patients were randomized in a 1:1 ratio to LuPSMA (n = 99) or cabazitaxel (n = 101). Study treatment occurred at 11 clinical locations in Australia. 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, AEs, and OS.
At the time of the data analysis, there were 173 progression events, 90 and 83 in the LuPSMA and cabazitaxel cohorts, respectively. LuPSMA delayed progression versus cabazitaxel (HR, 0.63; P = .0028), with a comparable benefit observed in radiographic progression-free survival (PFS; HR, 0.64; P = .0070) and PSA-PFS (HR, 0.60; P = .0017).
The safety analysis included 98 men in the LuPSMA arm and 85 in the cabazitaxel arm. Grade 3/4 AEs occurred in 33% (n = 32) and 53% (n =45) of the 2 arms, respectively.
1. Novartis announces positive result of phase III study with radioligand therapy 177Lu-PSMA-617 in patients with advanced prostate cancer. Published online March 23, 2021. Accessed March 23, 2021. https://bit.ly/397IZ1i.
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. 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.