Novartis Highlights 177Lu-PSMA-617 Radioligand Therapy Significantly Delays Deterioration in Health-Related Quality of Life and Pain in Advanced Prostate Cancer

September 18, 2021 /BioonBIOON/ --Novartis(Novartis) recently at the 2021 European MedicalTumorannounced at the European Society for Medical Oncology (ESMO) Virtual CongressTargeted Radioligand Therapy 177Lu-PSMA-617 for Prostate CancerPositive health-related quality of life (HRQoL) data from the pivotal Phase 3 VISION study. The study was conducted in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who had previously received multiple lines of therapy, evaluating 177Lu-PSMA-617 in combination with standard of care (SOC) versus SOC alone.

Many patients with mCRPC experience functional decline and significant pain.. The HRQoL data presented at the meeting showed:Compared with the SOC treatment group, the 177Lu-PSMA-617 + SOC treatment group significantly delayed the deterioration of these intolerable symptoms.No new or unexpected safety issues were observed, including changes in creatinine clearance.

Specifically, HRQoL and post hoc analyses showed: compared with the SOC treatment group, the 177Lu-PSMA-617 + SOC treatment groupThe estimated risk of deterioration in HRQoL (measured using the Functional Assessment of Cancer Therapy-Prostate [FACT-P] scale) from baseline was reduced by 54%.(HR=0.46; 95% CI: 0.35–0.61). In addition, compared with the SOC treatment group, the 177Lu-PSMA-617 + SOC treatment groupThe estimated risk of pain intensity worsening relative to baseline (measured using the Brief Pain Inventory-Short Form [BPI-SF] scale) was reduced by 55%.（HR=0.45，95%CI:0.33-0.60）。

NovartisTumorJeff Legos, Global Head of Hematology Development and Executive Vice President, stated: “Patients with mCRPC face numerous complications associated with advanced disease that can significantly impact their quality of life. These new data highlight the potential impact of 177Lu-PSMA-617 as a potential new treatment option on quality of life, extending beyond the previously reported improvements in overall survival (OS) and radiographic progression-free survival (rPFS).”

Previously, the United StatesFDABreakthrough Therapy Designation (BTD) has been granted for 177Lu-PSMA-617 in the treatment of metastatic castration-resistant prostate cancer (mCRPC). Metastatic prostate cancer carries a poor prognosis, with a 5-year survival rate of approximately 30%.

VISION was an international, prospective, randomized, open-label, multicenter study conducted in 831 patients with metastatic castration-resistant prostate cancer (mCRPC) who experienced disease progression following prior taxane and androgen receptor-directed therapy (ARDT) and were PSMA-PET scan-positive. The study evaluated the efficacy and safety of 177Lu-PSMA-617 (administered as an intravenous infusion of 7.4 GBq every 6 weeks for up to 6 cycles) in combination with best standard of care (SOC), compared with SOC alone.

The results of this study have been published in the international medical journal *The New England Journal of Medicine* (NEJM), for details, see:Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. The results showed that,The study met both primary endpoints. Compared with the SOC group, the 177Lu-PSMA-617 + SOC group demonstrated: (1) significantly prolonged overall survival (median OS: 15.3 months vs. 11.3 months; p < 0.001), with a 38% reduction in the risk of death (HR = 0.62; 95% CI: 0.52–0.74); (2) significantly prolonged radiographic progression-free survival (median rPFS: 8.7 months vs. 3.4 months; p < 0.001), with a 60% reduction in the risk of radiographic progression or death (HR = 0.40; 99.2% CI: 0.29–0.57).

Furthermore, compared with the SOC treatment group, the 177Lu-PSMA-617 + SOC treatment group: (1) demonstrated a significantly delayed time to first symptomatic skeletal event (SSE) or death (median time: 11.5 months vs. 6.8 months; p < 0.001; α = 0.05; HR = 0.50 [95% CI: 0.40, 0.62]); and (2) achieved a significantly higher overall response rate (ORR: 29.8% vs. 1.7%; p < 0.001). In terms of safety, 9.3% of patients in the 177Lu-PSMA-617 + SOC treatment group experienced serious drug-related treatment-emergent adverse events, compared with 2.4% in the SOC treatment group.

The above data confirm the potential of 177Lu-PSMA-617 to improve clinical outcomes in patients with PSMA-positive mCRPC. Based on these study results,NovartisA marketing application for 177Lu-PSMA-617 is planned to be submitted in the United States and the European Union in the second half of 2021.

Prostate cancer is a cancer that occurs in the prostate, a small walnut-shaped gland in the male pelvis. In castration-resistant prostate cancer (CRPC), despite hormone therapy to lower testosterone levels, the tumor continues to show signs of growth, such as elevated prostate-specific antigen (PSA) levels. In metastatic CRPC (mCRPC),TumorIt spreads to other parts of the body, such as adjacent organs or bone, and remains unresponsive to hormone therapy. The 5-year survival rate for patients with mCRPC is approximately 15%.

Despite advances in the treatment of prostate cancer, there remains a very high unmet medical need for new targeted therapies for patients with mCRPC. Over 80% of prostate cancerTumorhighly expresses a phenotypic biomarker called prostate-specific membrane antigen (PSMA), making it a promisingDiagnosisTargets (imaged via positron emission tomography [PET] scans) and therapeutic targets for radioligand therapy.

177Lu-PSMA-617 is a PSMA-targeted radioligand therapy developed for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This drug is a precision cancer treatment that combines a targeting compound (ligand) with a therapeutic radioisotope (radionuclide). Following intravenous administration, 177Lu-PSMA-617 binds to prostate cancer cells expressing PSMA (a transmembrane protein), resulting in higher drug uptake in tumors compared to normal tissues. Once bound, the radiation (beta particles) emitted from the radioisotope damages...Tumorcells, disrupting their ability to replicate and/or triggering cell death. The radiation from radioisotopes acts only over a very short range to limit damage to surrounding cells.

Currently, Novartis is also conducting two additional clinical trials to evaluate the use of 177Lu-PSMA-617 for the early treatment of metastatic prostate cancer, including in taxane-naïve mCRPC (PSMAfore) and metastatic hormone-sensitive prostate cancer (mHSPC) (PSMAddition). Furthermore,Novartisis also evaluating the potential of 177Lu-PSMA-617 for early-stage prostate cancer treatment. (Bioon.com)

Original Source:Novartis reports positive health-related quality of life data for 177Lu-PSMA-617 radioligand therapy in patients with advanced prostate cancer at ESMO 2021