1826P - Lutetium-177-PSMA in pre- and post-taxane mCRPC setting: Results from a phase II clinical trial

Background

Lutetium-177(177Lu)-PSMA-617 prolonged progression-free survival (PFS) and overall survival (OS) versus standard of care in metastatic castration-resistant prostate cancer (mCRPC) patients, as shown in the phase III VISION trial; in this trial, patients already received taxane-based chemotherapy. Here we report the analysis from a phase II trial of 177Lu-PSMA617 administered in pre- and post-taxane mCRPC settings.

Methods

In the IRST-185.03 study, which is an open-label, single-center, phase 2 prospective trial, 145 mCRPC patients were enrolled between April 2017 and October 2022. 142 patients received up to 6 cycles of 177Lu-PSMA617 - radiolabelled by IRST Radiopharmacy - every 6 weeks, with a mean dose of 17.5 GBq (up to 33 GBq of total dose). Best biochemical response (BBR), defined as ≥50% PSA reduction from baseline, is the main clinical endpoint of the trial, whilst PFS, OS, and safety are the main secondary endpoints.

Results

Among 142 evaluable patients, 100 patients received at least one cycle of taxane-based chemotherapy for castration-sensitive and castration-resistant disease (post-taxane group), whilst 42 were taxane-naïve (pre-taxane group). Baseline clinical characteristics of the two groups were balanced in terms of age, Gleason score, and previous ARSI, except for a higher proportion of ECOG PS 1-2 patients in the post- versus pre-taxane group (42 and 16.7%, respectively). At the first interim analysis, after a median follow-up of 28.8 months, BBR was obtained in 23 (54.8%) and 35 (35%) patients in the pre- and post-taxane groups, respectively. Median PFS was 8.5 and 6.0 months while median OS was 35.1 and 12.6 months in the pre- and post-taxane groups, respectively. Concerning safety, anemia was the most common adverse event (G1: 71.4 and 69%, G2: 9.6 and 11%. G3: 0 and 5%, in the pre- and post-taxane groups, respectively). No G3 adverse events were recorded in the pre-taxane group.

Conclusions

177Lu-PSMA617 could be a valid therapeutic choice in taxane-naïve mCRPC patients, especially in those who are deemed frail and unfit for chemotherapy.

Clinical trial identification

EudraCT/RSO 2016-002732-32, Start date: 2017-02-15.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

E.F. Giunta: Financial Interests, Personal, Other, Travel fees: Janssen Cilag. N. Brighi: Financial Interests, Personal, Other: Ipsen, Novartis, Janssen Cilag, Pfizer; Financial Interests, Personal, Advisory Board: BMS. C. Lolli: Financial Interests, Personal, Advisory Board: Ipsen, BMS, MSD. G. Schepisi: Financial Interests, Personal, Advisory Board: Bayer, BMS, Ipsen. U.F.F. De Giorgi: Financial Interests, Personal, Advisory Board: Pfizer, BMS, MSD, PharmaMar, Astellas, Bayer, Ipsen, Novartis, Eisai, Janssen; Financial Interests, Personal, Invited Speaker: Roche, BMS, Clovis Oncology, AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca, Sanofi, Roche. All other authors have declared no conflicts of interest.