177Lu-PSMA-617 Earns FDA Breakthrough Designation for Metastatic Castration-Resistant Prostate Cancer

Radioligand therapy 177Lu-PSMA-617 receives breakthrough designation from the FDA based on better overall survival outcomes in patients with metastatic castration-resistant prostate cancer.

Breakthrough therapy designation was granted by the FDA to 177Lu-PSMA-617 for treatment of patients with metastatic castration-resistant prostate cancer (mCRPC), according to the drug’s developer, Novartis.

This designation was granted based on positive data from the phase 3 VISION study (NCT03511664) which investigated 177Lu-PSMA-617 vs standard of care (SOC) for patients with progressive PSMA-positive mCRPC. The study found that those who received 177Lu-PSMA-617 had improved overall survival (OS) as well as radiographic progression-free survival (rPFS).

Findings presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting showed that the addition of 177Lu-PSMA-617 led to roughly a 40% reduction of risk of death as well as a 4-month improvement in median OS compared with SOC (HR, 0.62; 95% CI, 0.52-0.74; P <.001). For OS, the median was 15.3 months in the 177Lu-PSMA-617 arm vs11.3 months in the SOC arm.

Investigators also found that radioligand therapy led to a 5.3-month improvement in rPFS, equating to a 60% reduction in risk of progression or death (HR, 0.40; 99.2% CI, 0.29-0.57; P <.001). The median rPFS was 8.7 vs 3.4 months, respectively.

Secondary end points were statistically significant and favored the 177Lu-PSMA-617 arm. The objective response and disease control rates were 29.8% versus 1.7% and 89% versus 66.7%, respectively.

While 177Lu-PSMA-617 was well tolerated, some common adverse effects were fatigue (49.1% vs 29.3% in the control arm), bone marrow suppression (47.4% vs 17.6%, respectively), dry mouth (39.3% vs 1%), nausea/vomiting (39.3% vs 17.1%), kidney effects (8.7% vs 5.9%), second primary malignancies (2.1% vs 1%), and intracranial bleeding (1.3% vs 1.5%). There were no treatment related deaths.

This study included 831 patients who were randomized in a 2:1 fashion to the treatment arms. The open-label trial monitored patients for 6 to 10 months during treatment, with physicians being allowed to choose best supportive care with the exception of investigational agents, cytotoxic chemotherapy, other systemic radioisotopes, and hemi-body radiotherapy. Long-term follow-up will collect survival data and treatment updates with the addition of adverse event and blood monitoring. The coprimary end points of this study were OS and rPFS.

“This trial shows an alternative to traditional therapies by using radiation targeted to the PSMA antigen. So, it could be delivered directly to the prostate cancer cells, and by doing that, survival was significantly improved,” said ASCO President Lori J. Pierce, MD, FASTRO, FASCO.

Studies involving 177Lu-PSMA-617 radioligand therapy are ongoing, which may allow use of the agent in earlier phases of metastatic prostate cancer. It is also being studied for use in pre-taxane mCRPC setting as well as the metastatic hormone sensitive setting.


Novartis Receives FDA Breakthrough Therapy Designation for Investigational 177Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer. News Release. Novartis. June 16, 2021. Accessed June 17, 2021. https://bit.ly/3vwr7W9