(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL between May 30th and June 3rd, 2025, was host to a prostate, testicular, and penile cancers poster session. Dr. Ashwani Sood presented the results of a randomized, phase II trial of 177Lu-PSMA-617 consolidation therapy post-docetaxel in patients with de novo, high-volume hormone-sensitive prostate cancer (mHSPC).
Patients with de novo, high volume mHSPC continue to have poor survival outcomes, despite treatment intensification in the 1st line setting with an androgen receptor pathway inhibitor (ARPI) +/- docetaxel.1,2 While ADT + docetaxel doublet therapy intensification is no longer recommended by the NCCN guidelines as 1st line therapy for de novo high volume mHSPC patients,3 there are limited options for such patients who continue to harbor residual disease following completion of the pre-determined 6 cycles of docetaxel.
177Lu-PSMA-617 has demonstrated survival benefits in the post-docetaxel + ARPI mCRPC setting.4,5 The objective of this study was to evaluate the efficacy and safety of 177Lu-PSMA-617 consolidative therapy following docetaxel therapy in patients with de novo, high-volume mHSPC.
This was an investigator-initiated, randomized, parallel-group, open-label, phase II randomized trial. The study design is summarized below. This trial included patients with de novo, high volume mHSPC who received 6 cycles of docetaxel + ADT and had residual disease (partial response or stable disease) with a PSA >0.2 ng/ml and PSMA-positive disease on 68Ga-PSMA-11 PET/CT (VISION criteria). Patients were randomized 1:1 to:
- Intervention: 177Lu-PSMA-617 (7.4 GBq) x 2 cycles every 6 weeks + standard of care therapy
- Control: Standard of care therapy alone
The primary endpoint is PSA ≤0.2 ng/ml at 6 months. Secondary endpoints are:
- Objective response rate (ORR)
- Radiographic progression-free survival (rPFS)
- PSA progression-free survival (PSA-PFS)
- Toxicity
- Overall survival (OS)
Thirty high volume mHSPC patients (15 in each arm) were recruited between January 2021 and May 2024. Patients in the intervention arm (177Lu-PSMA-617) had superior 6-months PSA ≤0.2 ng/ml responses (60% vs 13%; RR=4.5, p=0.008)
The median rPFS (18 vs 9 months) and PSA-PFS (15 vs 9 months) both favored the intervention arm.
No major grade 3–4 treatment-related adverse events were observed in the 177Lu-PSMA-617 arm. Dr. Sood acknowledged that larger phase III trials are needed to confirm the survival benefits of 177Lu-PSMA-617 consolidation following upfront ADT + docetaxel therapy.
Dr. Sood concluded that in de novo, high volume mHSPC patients treated with docetaxel and harboring residual disease (partial response or stable disease) on 68Ga-PSMA-11 PET/CT, 177Lu-PSMA-617 consolidation therapy for two cycles demonstrated significant improvements in biochemical response outcomes.
Presented by: Ashwani Sood, MBBS, DRM, DNB, Professor, Department of Nuclear Medicine, PGIMER, Chandigarh, India
Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.
References:- Hussain M, Tombal B, Saad F, et al. Darolutamide plus androgen-deprivation therapy and docetaxel in metastatic hormone-sensitive prostate cancer by disease volume and risk subgroups in the phase III ARASENS trial. J Clin Oncol. 2023; 41(20): 3595-3607.
- Sweeney CJ, Martin AJ, Stockler MR, et al. Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): An international, open-label, randomized, phase 3 trial. Lancet Oncol. 2023; 24(4): 323-334.
- Mohler JL, Antonarakis ES, Armstrong AJ, et al. Prostate cancer, version 2.2024, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2024; 22(4) :315–399.
- Sartor O, de Bono J, Chi KN et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021; 385(12): 1091-1103.
- Hofman MS, Emmett L, Sandhu S, et al. [(177)Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): A randomized, open-label, phase 2 trial. Lancet. 2021; 397(10276): 797-804.