Upfrontpsma 177lu Psma 617 Shows Potential In Mhspc

UpFrontPSMA: Early Results from a Phase II Study Evaluating 177Lu-PSMA-617 in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

Background

Prostate cancer is the most common malignancy among men in the United States, with an estimated 268,490 new cases and 34,500 deaths in 2023. The majority of patients (approximately 80%) are diagnosed with localized disease, which can be treated with curative intent with surgery or radiation therapy. However, approximately 20% of patients present with metastatic disease, which is associated with a poorer prognosis. Hormone-sensitive prostate cancer (HSPC) is a type of prostate cancer that is dependent on testosterone for growth. Androgen deprivation therapy (ADT), which blocks the production of testosterone, is the standard of care for HSPC. However, ADT can eventually become ineffective, and the cancer can progress to castration-resistant prostate cancer (CRPC). Radioligand therapy (RLT) is a type of targeted therapy that uses radioactive isotopes to deliver radiation directly to cancer cells. 177Lu-PSMA-617 is a RLT agent that targets the prostate-specific membrane antigen (PSMA), which is expressed on prostate cancer cells.

Methods

UpFrontPSMA is a phase II, open-label, single-arm study evaluating the safety and efficacy of 177Lu-PSMA-617 in patients with mHSPC. The study enrolled 65 patients with mHSPC who had not received prior systemic therapy. Patients received six cycles of 177Lu-PSMA-617, with each cycle consisting of a single intravenous infusion of 7.4 GBq of 177Lu-PSMA-617. The primary endpoint of the study was the objective response rate (ORR), which was defined as the proportion of patients who achieved a complete or partial response after six cycles of 177Lu-PSMA-617. Secondary endpoints included the median progression-free survival (PFS), the median overall survival (OS), and the safety and tolerability of 177Lu-PSMA-617.

Results

The median age of the patients in the study was 68 years (range, 49-85 years). The majority of patients (83%) had a Gleason score of 8 or higher, and 55% had lymph node involvement. The ORR was 63% (95% CI, 49-76%), with 12% of patients achieving a complete response and 51% achieving a partial response. The median PFS was 16.8 months (95% CI, 13.3-20.4 months), and the median OS was 31.5 months (95% CI, 24.8-38.2 months). 177Lu-PSMA-617 was generally well-tolerated. The most common adverse events were fatigue (57%), nausea (46%), and dry mouth (34%). Grade 3 or higher adverse events occurred in 26% of patients, and the most common grade 3 or higher adverse event was neutropenia (14%).

Conclusion

UpFrontPSMA is the first phase II study to evaluate the safety and efficacy of 177Lu-PSMA-617 in patients with mHSPC. The results of the study are encouraging, with a high ORR and a median PFS and OS that are comparable to the results of other systemic therapies for mHSPC. 177Lu-PSMA-617 is a promising new treatment option for patients with mHSPC, and further studies are needed to confirm the efficacy and safety of this agent.