177Lu-PSMA-617 Improves Progression-free Survival and Patient-reported Outcomes Compared to Cabazitaxel for Men with Metastatic Castration-resistant Prostate Cancer

The phase 2 TheraP clinical trial demonstrated that a small molecule delivering beta radiation, 177Lu-PSMA-617, was able to generate more prostate-specific antigen (PSA) responses of at least 50% reduction compared to the third-generation taxane cabazitaxel for men with metastatic castration-resistant prostate cancer (mCRPC). In an updated analysis presented during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium, Dr. Michael S. Hofman and colleagues found the patients receiving 177Lu-PSMA-617 had improved progression-free survival, fewer grade 3-4 adverse events, and some improvements in patient-reported outcomes (PROs) compared to cabazitaxel.

177Lu-PSMA-617 is a therapy that targets cells expressing prostate-specific membrane antigen (PSMA), a unique mechanism compared to traditional chemotherapeutics. TheraP demonstrated a 1-year progression-free survival rate of 19% for 177Lu-PSMA-617 compared to 3% for cabazitaxel (hazard ratio, 0.63; 95% confidence interval, 0.46-0.86; P=0.003). While many patients progressed, the results are a step forward for patients with mCRPC who have previously failed multiple other therapies. The lower rate of grade 3-4 adverse events (33% vs. 53%) and improvements in PROs related to fatigue, social functioning, insomnia, and diarrhea suggest patients may better tolerate 177Lu-PSMA-617 treatment. The findings support evaluation of 177Lu-PSMA-617 in larger phase 3 trials and potential combination therapies in the future.

References:

J Clin Oncol 39, 2021 (suppl 6; abstr 6)

Hofman MS, Emmett L, Sandhu S, et al. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021 Feb 11:S0140-6736(21)00237-3.