Adding adaptive-dosing of [¹⁷⁷Lu]Lu-PSMA-617 (¹⁷⁷Lu-PSMA-617) to enzalutamide improved prostate specific antigen-progression-free survival (PSA-PFS), and the PSA50% and PSA90% response rates among patients with metastatic castration-resistant prostate cancer.

These results were presented by Louise Emmett, MBChB, FRACP, MD, St. Vincent’s Hospital, New South Wales, Australia, at the 2023 European Society for Medical Oncology Annual Congress in Madrid, Spain.

This investigator-initiated, phase 2 trial enrolled 162 patients with metastatic castration-resistant prostate cancer who had not been previously treated with chemotherapy or androgen receptor pathway inhibitors and had at least 2 high risk features for enzalutamide failure. Patients were randomized on a 1-to-1 basis to receive either enzalutamide alone (n = 79), or with adaptive dosing ¹⁷⁷Lu-PSMA-617 (n = 83). The primary end point of this study was PSA-PFS, with secondary end points including radiological PFS, PSA50% and PSA90% response rates, adverse events, and overall survival.

In her presentation at the 2023 ESMO Annual Congress, Dr Emmett stated the adaptive dosing for ¹⁷⁷Lu-PSMA-617 was an important part of this trial. In the ¹⁷⁷Lu-PSMA-617 arm, patients received the first 2 doses of ¹⁷⁷Lu-PSMA-617 followed by a PSMA PET scan on day 92, which was centrally reviewed. If persistent disease was identified on that scan, patients went on to receive a further 2 doses of ¹⁷⁷Lu-PSMA-617, for a total of 4 doses. In this trial, 81% of patients on the 177Lu-PSMA-617 arm received a total of 4 doses of ¹⁷⁷Lu-PSMA-617.

With a median follow-up duration of 20 months, PSA-PFS was longer for patients in the ¹⁷⁷Lu-PSMA-617 arm compared to enzalutamide alone (13 months vs 7.8 months; hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.29 to 0.63; P < .001). Median radiologic PFS was 16 months on the ¹⁷⁷Lu-PSMA-617 arm, vs 12 months on the enzalutamide along arm (HR, 0.67; 95% CI, 0.44 to 1.01). PSA50% and PSA90% response rates were also higher in the ¹⁷⁷Lu-PSMA-617 arm (93% and 78% vs 68% and 37%). Serious adverse events were observed in 33% of patients in the ¹⁷⁷Lu-PSMA-617 arm, and 35% of patients in the enzalutamide alone arm.

Dr Emmett concluded that this trial “provides strong evidence of enhanced anticancer effect with the combination of enzalutamide and [¹⁷⁷Lu-PSMA-617] based on the primary end point PSA-PFS.” She added that while this trial administered 2 to 4 doses of ¹⁷⁷Lu-PSMA-617, “4 to 6 doses may further improve progression-free survival.”

Source:

Emmett L, Subramaniam S, Crumbaker M, et al. Enzalutamide and ¹⁷⁷Lu-PSMA-617 in poor-risk, metastatic, castration-resistant prostate cancer (mCRPC): A randomised, phase II trial: ENZA-p (ANZUP 1901). Presented at 2023 ESMO Annual Congress; October 20-24, 2023; Madrid, Spain. LBA84.