FDA Grants Priority Review to 177Lu-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer


The FDA has granted a priority review designation to a new drug application for lutetium-177-PSMA-617 for use in the treatment of patients with metastatic castration-resistant prostate cancer following androgen receptor pathway inhibition and taxane-based chemotherapy.

The FDA has granted a priority review designation to a new drug application for lutetium-177 (177Lu)-PSMA-617 for use in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) following androgen receptor pathway inhibition and taxane-based chemotherapy.1

The decision was based on findings from the phase 3 VISION trial (NCT03511664), which showed that when the investigational targeted radioligand therapy was added to standard of care, it resulted in a significant improvement in overall survival (OS) and radiographic progression-free survival (PFS) over SOC alone in patients with progressive prostate-specific membrane antigen (PSMA)–positive mCRPC.2

At a median follow-up of 20.9 months, the median overall survival with 177Lu-PSMA-617 (n = 551) was 15.3 months vs 11.3 with SOC alone (n = 280; HR, 0.62; 95% CI, 0.52-0.74; P < .001). The median PFS in the investigative (n = 385) and control arms (n = 196) was 8.7 months and 3.4 months, respectively (HR, 0.40; 99.2% CI, 0.29-0.57; P < .001).

The regulatory agency is expected to decide on the application in the first half of 2022, under the Prescription Drug User Fee Act.

The open-label, international phase 3 trial enrolled patients with CRPC and at least 1 metastatic lesion on baseline computed tomography, magnetic resonance imaging, or bone-scan imaging. To be eligible for enrollment, patients also needed to have experienced progressive disease following prior treatment with both 1 or more approved androgen receptor–pathway inhibitors and with 1 or more taxane-based regimens. They also needed to have PSMA positivity, an ECOG performance status of 0 to 2, a life expectancy of 6 months or longer, and acceptable organ and bone marrow function.

Study participants were randomized 2:1 to receive either 177Lu-PSMA-617 plus SOC or SOC alone. SOC options could not include cytotoxic chemotherapy, systemic radioisotopes, immunotherapy, or agents that were investigational around the time that the study was designed, such as olaparib (Lynparza). Options could include approved hormonal treatments like abiraterone acetate (Zytiga) and enzalutamide (Xtandi), bisphosphonates, radiation, denosumab, or glucocorticoids.

Those on the investigative arm received intravenous infusions of the radioligand therapy at a dose of 7.4 GBq once very 6 weeks for 4 cycles. Two additional cycles could be given, at physician discretion, to those who exhibited response to treatment. Participants were still given SOC, with or without 177Lu-PSMA-617, until progressive disease, intolerable toxicity, of lack of clinical benefit.

The primary end points of the trial were imaging-based PFS and OS. Key secondary end points comprised objective response rate, disease control rate, the time to first symptomatic skeletal event, safety, health-related quality of life, and biomarker outcomes.

A total of 831 patients were randomized to receive 177Lu-PSMA-617 plus SOC (n = 551) or SOC alone (n = 280). The median age across the arms in all patients who underwent randomization was 70.8 years, 92.4% had an ECOG performance status of 0 or 1, and the majority had disease in the bone. The median PSA level in the investigative arm was 77.5 ng/mL vs 74.6 ng/mL in the control arm. The median time since diagnosis was 7.4 years in both arms, and just under half of patients on both arms had prior prostatectomy.

Moreover, across the arms, 49.9% of patients had 1 prior androgen receptor pathway inhibitor regimen, 42.2% had 2 prior regimens, and 8.0% of patients received more than 2 prior regimens. Regarding prior taxane therapy, 57.4% had 1 prior regimen and 41.8% had 2 prior regimens; moreover, 97.2% had received docetaxel, and 38.1% received cabazitaxel.

Of the 581 total patients included in the analysis set, the median time to first symptomatic skeletal event or death was 11.5 months and 6.8 months in the 177Lu-PSMA-617/SOC arm and the SOC-alone arms, respectively (HR, 0.50; 95% CI, 0.40-0.62; P < .01).

Of the 248 patients who had measurable target lesions per RECIST v1.1 criteria, 9.2% achieved a complete response with 177Lu-PSMA-617 vs 0% of those who received SOC alone; partial responses were reported in 41.8% and 3% of patients, respectively.

Additionally, more patients who received the radionuclide therapy experienced confirmed decreases in their PSA levels of at least 50% and 80% from baseline. The time to deterioration in the FACT-P total score and BPI-SF pain intensity score were also reported to favor the investigative group over the control group.

Regarding safety, all-grade adverse effects (AEs) were experienced by 98.1% and 82.9% of those on the investigative and control arms, respectively; 52.7% and 38.0% of patients, respectively, experienced grade 3 or higher effects.

The most common all-grade AEs reported in the radionuclide and control arms, respectively, were fatigue (43.1% vs 22.9%), dry mouth (38.8% vs 0.5%), nausea (35.3% vs 16.6%), anemia (31.8% vs 13.2%), back pain (23.4% vs 14.6%), arthralgia (22.3% vs 12.7%), decreased appetite (21.2% vs 14.6%), constipation (20.2% vs 11.2%), diarrhea (18.9% vs 2.9%), vomiting (18.9% vs 6.3%), thrombocytopenia (17.2% vs 4.4%), lymphopenia (14.2% vs 3.9%), and leukopenia (12.5% vs 2.0%).

Frequent grade 3 or higher AEs reported in the investigative and control arms include fatigue (5.9% vs 1.5%, respectively), nausea (1.3% vs 0.5%), anemia (12.9% vs 4.9%), back pain (3.2% vs 3.4%), arthralgia (1.1% vs 0.5%), decreased appetite (1.9% vs 0.5%), constipation (1.1% vs 0.5%), diarrhea (0.8% vs 0.5%), vomiting (0.9% vs 0.5%), thrombocytopenia (7.9% vs 1.0%), lymphopenia (7.8% vs 0.5%), and leukopenia (2.5% vs 0.5%).

Two studies are currently examining 177Lu-PSMA-617 in earlier lines of treatment for patients with metastatic prostate cancer. In the phase 3 PSMAfore trial (NCT04689828), investigators are evaluating the clinical utility of the radionuclide therapy vs androgren receptor–directed therapy in the treatment of patients with progressive metastatic CRPC. In the phase 3 PSMAddition trial (NCT04720157), 177Lu-PSMA-617 plus SOC is being compared with SOC alone in patients with metastatic hormone-sensitive prostate cancer.


  1. FDA grants priority review for investigational targeted radioligand therapy 177Lu-PSMA-617 for patients with metastatic castration-resistant prostate cancer (mCRPC). News release. Novartis. September 28, 2021. Accessed September 30, 2021. https://bit.ly/2Y0GCKY
  2. 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. doi:10.1056/NEJMoa2107322
Related Videos
Clara Hwang, MD
Clara Hwang, MD
Joshi Alumkal, MD
Clara Hwang, MD
Clara Hwang, MD
Alexandra Sokolova, MD
Expert on prostate cancer
Experts on prostate cancer
Neeraj Agarwal, MD
Zachery Roger Reichert, MD, PhD
Related Content