LuPSMA Therapy Prolongs Survival in Progressive PSMA-Positive mCRPC

¹⁷⁷Lu-PSMA-617, a targeted radioligand therapy, demonstrated improvement in both radiographic progression-free survival (rPFS) and overall survival (OS) as treatment of patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) compared with best standard ofcare (SOC) alone in the phase 3 VISION trial (NCT03511664), according to a press announcement from Novartis.¹

The key primary end points of the study were achieved with this result and, therefore, ¹⁷⁷Lu-PSMA-617 could become a targeted therapy to help >80% of patients with advanced prostate cancer. In addition, a consistent safety profile was observed for ¹⁷⁷Lu-PSMA-617 compared with previous reports.

“Patients with metastatic castration-resistant prostate cancer have a less than 1 in 6 chance of surviving 5 years and need new treatment options. 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,” said John Tsai, head of Global Drug Development and chief medical officer, Novartis.

The company also announced that results from the VISION trial will be presented during an upcoming medical meeting.

Based on a prior phase 2 study of ¹⁷⁷Lu-PSMA-617 as treatment of mCRPC, adverse events (AEs) that can occur with the agent include neutropenia, thrombocytopenia, dry mouth, diarrhea, dry eye, dysgeusia, neutropenia, fatigue, nausea, anemia, and vomiting.²

¹⁷⁷Lu-PSMA-617 combines a targeted ligand with a therapeutic radioisotope. Its mechanism of action allows it to bind to prostate cancer cells that express PSMA. Binding to these cell trigger tumor cell damage and cell death, but limits damage to non-malignant cells.¹

In prostate cancer, there remains an unmet medical need to provide more effective options for patients with metastatic and castration-resistant disease. Preclinical research of ¹⁷⁷Lu-PSMA-617 suggested that the imaging tool could provide important diagnostic information to help identify patients who could benefit from radioligand therapy.

In the international, prospective, randomized, open-label, multicenter VISION study, investigators assess the safety and efficacy of ¹⁷⁷Lu-PSMA-617, which is given via intravenous infusion every 6 weeks for a maximum of 6 cycles in combination with the investigator’s best SOC option and compared with best SOC alone. The patients whose scans were positive for mCRPC and whose disease progressed after prior taxane and androgen receptor-directed therapy were randomized in a 2:1 fashion. A total of 831 patients were enrolled.

During the study, patients were monitored for a 6- to 10-month period for survival, disease progression, and AEs. During follow-up, investigators collect updates related to the study end points as well as blood samples for hematology and chemistry testing. Every 3 months, study subjects were contacted for 24 months or until the overall censoring rate for survival reduces to a level identified in the protocol. Finally, a visit occurs at the end of treatment, which is roughly 30 days following the last use of ¹⁷⁷Lu-PSMA-617.

Patients were eligible to be included in the VISION study given they were at least 18 years of age or older with disease confirmed by either histology, cytology, or pathology, an ECOG performance status of 0 or 1, and a life expectancy of at least 6 months. Patients were also required to have document progressive disease, a castrate level of serum/plasma testosterone, and adequate organ function. Patients were excluded from the study if they had prior treatment with strontium-89, samarium-153, rhenium-186, rhenium-188, radium-223, hemi-body irradiation, prior treatment with a PSMA-targeted radioligand, or previous treatment with any systemic anticancer therapy. Comorbidities that may interfere with study treatment also caused some patients to be excluded from 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. https://bit.ly/3tNFpBs}

_{2. Hofman MS, Emmett L, Sandhu SK, et al. TheraP: A randomised phase II trial of 177Lu-PSMA-617 (LuPSMA) theranostic versus cabazitaxel in metastatic castration resistant prostate cancer (mCRPC) progressing after docetaxel: Initial results (ANZUP protocol 1603). J Clin Oncol. 2020;38(suppl):5500. doi:10.1200/JCO.2020.38.15_suppl.5500}