Lutetium-177 PSMA-617 (LuPSMA) has shown promising results in treating metastatic castration-resistant prostate cancer (mCRPC). Data from the Phase III PSMAfore trial and an expanded access program (EAP) in the U.S. highlight its efficacy and safety, offering new hope for patients with limited treatment options.
PSMAfore Trial: LuPSMA vs. ARPI Change
The PSMAfore trial, a Phase III study, compared LuPSMA to a change in androgen receptor pathway inhibitor (ARPI) in taxane-naive patients with mCRPC who had progressed on a prior ARPI. The trial enrolled 468 patients across Europe and North America, randomizing them to receive either LuPSMA or a change to abiraterone or enzalutamide.
The primary analysis revealed a median radiographic progression-free survival of 9.30 months in the LuPSMA group compared to 5.55 months in the ARPI-change group (HR = 0.41, P < .0001). Updated analysis with longer follow-up (median 24.11 months) showed a median radiographic progression-free survival of 11.60 months for LuPSMA versus 5.59 months for ARPI change (HR = 0.49).
Michael J. Morris, MD, of Memorial Sloan Kettering Cancer Center, the corresponding author for The Lancet article, noted that LuPSMA offers an effective treatment alternative for patients with PSMA-positive mCRPC who are being considered for a change of ARPI after progression on a previous ARPI.
Safety Profile
The PSMAfore trial also demonstrated a favorable safety profile for LuPSMA. Grade ≥ 3 adverse events occurred in 36% of patients in the LuPSMA group and 48% in the ARPI group. The most common adverse event in both groups was anemia (6% vs 7%). Treatment discontinuation due to adverse events was similar in both groups (6% vs 5%).
Expanded Access Program (EAP) Data
An expanded access program (EAP) in the U.S. provided LuPSMA to eligible patients before regulatory approval. A study evaluating the efficacy and safety of LuPSMA within the EAP included 117 patients with mCRPC. These patients were more heavily pretreated and had worse performance status than those in the VISION trial. Despite this, the EAP patients achieved similar PSA response rates (42% vs. 46%) and overall survival (median: 15.1 vs. 15.3 months) compared to the VISION trial patients.
The EAP data suggests that LuPSMA can be effective even in later stages of mCRPC. The safety profile was also similar between the EAP and VISION trial patients, with comparable rates of grade 3 or higher anemia, thrombocytopenia, and neutropenia.
Implications for mCRPC Treatment
These findings suggest that LuPSMA is a viable treatment option for taxane-naive mCRPC patients who have progressed on ARPI therapy. The PSMAfore trial demonstrated superior radiographic progression-free survival with LuPSMA compared to ARPI change, and the EAP data supports its use even in heavily pretreated patients. With its manageable safety profile and significant clinical benefits, LuPSMA represents a valuable addition to the mCRPC treatment landscape.
