The latest trial results are based on a larger patient population and were reported at the 2019 ASCO Genitourinary Cancers Symposium.
The investigational radiolabeled small molecule that targets prostate-specific membrane antigen (PSMA), lutetium-177 PSMA-617 (LuPSMA), conferred a high response rate among a small group of men with metastatic castration-resistant prostate cancer in a single-arm, single-center, phase II trial. Results from an initial group of 30 patients who received LuPSMA were reported previously. The updated trial results are based on a larger patient population and were reported at the 2019 ASCO Genitourinary Cancers Symposium.
“[The trial] is exciting for a number of reasons,” Scott Tagawa, MD, MS, medical director of the Genitourinary Oncology Program at Weill Cornell Medicine and NewYork-Presbyterian, told Cancer Network during an interview. He explained that the field has been looking at PSMA as a therapeutic target for prostate cancer for “decades,” and the trial is “the first prospective study with a lutetium-radiolabeled small molecule.”
The trial enrolled 50 eligible men with metastatic castration-resistant prostate cancer that progressed after standard treatments. All patients had high PSMA expression and received up to 4 cycles of LuPSMA every 6 weeks. The primary endpoints were prostate-specific antigen (PSA) response (per Prostate Cancer Clinical Trials Working Group Criteria) and toxicity (per Common Terminology Criteria for Adverse Events v4.3).
Patients had a median age of 71 years (range, 50 to 87 years), Gleason score of 8 (range, 6 to 10), PSA level of 189.8 µg/mL (range, 7.4 to 4022.4), and PSA doubling time of 2.6 months (range, –9.1 to 387.0). Common prior treatments were abiraterone or enzalutamide or both (90%), docetaxel (84%), and cabazitaxel (48%). Patients received a median number of 4 cycles of LuPSMA (range, 1 to 4) with a median administered radioactivity of 7.8 GBq per cycle (range, 4.0 to 8.9).
At a median follow-up of 23.5 months, 32 of 50 patients (64%; 95% CI, 50–77) achieved a PSA decline of at least 50%; of those patients, 22 (44%; 95% CI, 30–59) achieved a PSA decline of at least 80%. A total of 14 patients received additional cycles of LuPSMA after disease progression, and 9 of those patients (64%) achieved a PSA decline of at least 50%.
Patients had a median PSA progression-free survival (PFS) of 6.9 months (95% CI, 5.7–8.8), and those who achieved a PSA decline of more than 50% had a longer median PSA PFS than those who did not (8.3 vs 4.2 months; P < .001). Patients had a median overall survival (OS) of 13.3 months (95% CI, 10.5–18.0), and similarly, those who achieved a PSA decline of more than 50% had a longer median OS than those who did not (18.0 vs 8.7 months; P < .001).
The most common treatment-emergent grade 1 or 2 adverse events were dry mouth (66%), nausea (48%), and fatigue (36%). Treatment-emergent grade 3 or 4 thrombocytopenia (10%) and anemia (10%) were considered “infrequent.”
“Nothing really stands out that’s high grade or long term,” Tagawa said about the adverse events. “I think the drug is very safe.” He noted that a previous retrospective analysis by Rahbar and colleagues evaluated LuPSMA and showed that grade 1 or 2 dry mouth occurred in a minority of patients (8%), not the majority (66%). Given the prospective nature of the current trial, Tagawa is more likely to “believe” the prospective data.
In light of the positive trial results, two randomized, prospective trials are now underway: the phase III VISION trial, which is sponsored by Endocyte and will evaluate LuPSMA vs standard of care (ClinicalTrials.gov Identifier: NCT03511664); and the phase II TheraP trial, which is sponsored by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group and will evaluate LuPSMA vs cabazitaxel (ClinicalTrials.gov Identifier: NCT03392428).
“Overall this is a good study, and I’m glad that now multiple different places are doing prospective studies,” Tagawa said.