177Lu-PSMA-617 Improves OS and rPFS Over Best Standard of Care in Advanced Prostate Cancer

John Tsai

The addition of the targeted radioligand therapy 177Lu-PSMA-617 to best standard of care was found to significantly improve overall survival (OS) and radiographic progression-free survival (rPFS) over best standard care alone in patients with prostate specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC), meeting both primary end points of the phase 3 VISION trial (NCT03511664).¹

Moreover, the safety findings reported with the product proved to be consistent with what has been observed in prior clinical trials. The results from VISION will be shared at an upcoming medical conference and will be included in regulatory submissions in both the United States and the European Union, according to Novartis.

“Patients with mCRPC have a less than 1 in 6 chance of surviving 5 years and need new treatment options,” John Tsai, head of Global Drug Development and chief medical officer of Novartis, commented in a press release. “These groundbreaking data confirm our belief in the potential of ¹⁷⁷Lu-PSMA-617 to reimagine outcomes for these patients through phenotypic precision medicine. We intend to submit these data to regulatory authorities as soon as possible.”

Through the combination of a targeting compound that binds to markers expressed by tumors and a radioactive isotope and initiating DNA damage that hinders tumor growth and replication, radioligand therapy allows for the targeted delivery of radiation into the tumor that limits damage to surrounding normal tissue.

¹⁷⁷Lu-PSMA-617 combines a ligand with a radioactive particle. After the product is delivered to the bloodstream, the therapy binds to PSMA-expressing prostate cancer cells. Once bound, the radioisotope elicits emissions that damage tumor cells and hinder their capability of replicating and/or triggering cell death.

In the international, prospective, open-label, multicenter VISION trial, investigators set out to compare OS in patients with progressive PSMA-positive mCRPC who receive ¹⁷⁷Lu-PSMA-617 plus best standard care vs those given best standard of care alone.

To be eligible for enrollment, patients had to be at least 18 years of age, have an ECOG performance status of 0 to 2, have a life expectancy of longer than 6 months, and have histological, pathological, and/or cytological confirmation of prostate cancer, among other criteria.² If they received prior treatment with strontium-89, samarium-153, rhenium-186, rhenium-188, radium-223 (Xofigo), hemi-body irradiation, or prior PSMA-targeted radioligand treatment, they were excluded, as were those who received any systemic anticancer therapy.

Participants who had PSMA-positive scans were randomized 2:1 to receive either ¹⁷⁷Lu-PSMA-617 at 7.4 GBq via intravenous infusion very 6 weeks for a maximum of 6 cycles plus best standard of care or best standard of care only. Notably, investigators will determine what the best standard of care will entail, but it will exclude investigational agents, cytotoxic chemotherapy, other systemic radioisotopes, and hemi-body radiotherapy. Novel androgen axis drugs like abiraterone acetate (Zytiga) and enzalutamide (Xtandi).

Patients will be monitored throughout the 6- to 10-month treatment period for survival, disease progression, and adverse effects. In the long-term follow-up period, investigators will continue to look at survival, toxicities, and collect blood for hematology and chemistry testing. During this follow-up, patients will be contacted every 3 months for 24 months or until the overall censoring rate for survival drops to a level identified in the SAP.

Once the patient enters long-term follow-up, an end-of-treatment visit will be conducted; this should be done about 30 days following the last dose of ¹⁷⁷Lu-PSMA-617 or best standard of care but prior to the start of subsequent anticancer treatment outside of what is permitted on the study.

References

1. Novartis announces positive result of phase III study with radioligand therapy 177Lu-PSMA-617 in patients with advanced prostate cancer. News release. Novartis. March 23, 2021. Accessed March 23, 2021. http://bit.ly/318s5LJ
2. Study of 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer (VISION). ClinicalTrials.gov. Updated February 4, 2021. Accessed March 23, 2021. https://clinicaltrials.gov/ct2/show/NCT03511664