Similar overall survival, better patient-reported outcomes, and fewer adverse effects were observed when patients were treated with 177Lu-PSMA-617 vs cabazitaxel in metastatic castration-resistant prostate cancer.
177Lu-PSMA-617 compared with cabazitaxel (Javtana) had similar overall survival (OS), less adverse effects, and improved patient-reported outcomes in patients with metastatic castration-resistant prostate cancer, according to a presentation from the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.1
The TheraP trial (NCT03392428), the first randomized controlled trial of LuPSMA, previously met its primary end point of prostate-specific antigen (PSA) decrease of at least 50% from baseline.2 The treatment was also associated with fewer grade 3 or 4 adverse events than treatment with cabazitaxel.
Patients with metastatic castration-resistant prostate cancer that progressed after docetaxel, had PET imaging with 68Ga-PSMA-11 that showed high PSMA-expression, and 18F-FDG demonstrating no sites of disease of FDG-positive and PSMA-negative were eligible for inclusion in the TheraP trial. Patients were randomized to treatment with either LuPSMA (8.5-6GBq every 6 weeks for a maximum of 6 cycles) or cabazitaxel (20 mg/m2 every 3 weeks for a maximum of 10 cycles).
A total of 291 were screened for the study, of whom 200 were deemed eligible for inclusion; 99 were randomized to LuPSMA and 101 were randomized to cabazitaxel. Eighty patients were excluded after PSMA/FDG-PET (51 patients had standardized uptake value maximum < 20, 29 were discordant); follow-up was available in 61 patients (76%). In the cabazitaxel arm, 15 men withdrew from the trial after randomization. At a median follow-up of 36 months, 70/101 patients receiving cabazitaxel, 77/99 patients receiving LuPSMA, and 55/61 patients excluded after PSMA/FDG-PET had died.
Presenting the results, study author Michael S. Hoffman, MBBS (Hons), FRACP, FAANMS, discussed post-protocol treatments. In patients randomized to LuPSMA, 32% patients went on to receive cabazitaxel and 5% received additional LuPSMA, and in the cabazitaxel arm, 21% received additional cabazitaxel and 20% received LuPSMA.
Hoffman reported that progression-free survival (PFS) favored LuPSMA, with a restricted mean survival time (RSMT) of 7.1 months for LuPSMA (95% CI, 5.9-8.4) vs 5.0 months for cabazitaxel (95% CI, 4.2-5.8).
Regarding OS, “We were unable to detect a statistical or clinically significant difference in overall survival with LuPSMA,” said Hoffman, director of the Prostate Cancer Theranostics and Imaging Centre of Excellence at the Peter MacCallum Cancer Centre in Melbourne, Australia.
“Importantly, no additional safety signals were reported with regards to lutetium PSMA in this longer term follow-up,” Hoffman added.
The investigators also evaluated OS in the patients who were excluded due to screening failure; 61 of 80 patients consented to follow-up. The next line of treatment for these patients was cabazitaxel in 29 patients (48%), enzalutamide (Xtandi) in 4 patients, LuPSMA in 3 patients (5%), carboplatin in 3 patients (5%), other in 3 patients (5%) and mitoxantrone in 1 patient (2%). RMST was 18.8 months (95% CI, 16.8-20.8) in the randomized patients vs 11.0 months in the patients who failed screening (95% CI, 9.0-13.1).
Hoffman explained that the strengths of the study including its prospective, randomized, multicenter design, the fact that it had 3 years of follow-up, and that it had an active control arm. Limitations included the fact that post-protocol cross-over limit the investigators’ ability to observe OS difference. In addition, “TheraP was never powered for overall survival, and this is also significant with regards to withdrawals in the cabazitaxel arm in patients seeking to have lutetium therapy, which did not occur in the lutetium arm,” Hoffman said.
“The clinical implications are that lutetium PSMA has similar overall survival to cabazitaxel, a proven life-prolonging therapy, but with fewer adverse events and better patient-reported outcomes. But we should be clear that lutetium PSMA shows greater activity, and that’s not just confined to PSA response rates, because we see it with radiographic PFS and RECIST,” Hoffman added.
In his concluding remarks, Hoffman said, “The TheraP data supports the choice of 177Lu-PSMA-617 over cabazitaxel for patients with PSMA-positive, progressive mCRPC after docetaxel and androgen-receptor pathway inhibitor, on the basis of its higher PSA response rate, greater PFS benefit, quality of life benefits, favorable safety profile, dosing schedule 6 weeks vs 3 weeks, and similar survival outcomes to cabazitaxel.”