Clinical treatment found that in metastatic castration-resistant prostate cancer (mCRPC), the tumor spreads to other parts of the body, such as neighboring organs or bones, and there is still no response to hormone therapy. The 5-year survival rate of mCRPC patients is about 15%. Recently, the U.S. FDA granted targeted radioligand therapy Lu-177-PSMA-617 breakthrough drug qualification (BTD) for the treatment of metastatic castration-resistant prostate cancer.
Introduction to Lu-177 therapy
Drug name: Lu-177-PSMA-617
Other name: LuPSMA
R&D: Novartis (Novartis)
Consultant: United Cancer Centre of Hong Kong
Lu-177-PSMA-617 is a precision cancer treatment that combines a targeted compound (ligand) with a therapeutic radioisotope (radioactive particles). After injection into the bloodstream, Lu-177-PSMA-617 binds to prostate cancer cells expressing PSMA (a transmembrane protein), resulting in higher drug uptake by the tumor compared to normal tissue. Once bound, radiation from the radioisotope (beta particles) damages the tumor cells, impairing their replication ability and/or triggering cell death. The radiation from the radioisotope works only over a very short distance to limit damage to surrounding cells.
Lu-177 therapy research data
The FDA granted Lu-177-PSMA-617 BTD, based on the positive results of a key phase 3 VISION study. The study investigated the standard of care (SOC) of Lu-177-PSMA-617 and patients with progressive PSMA-positive mCRPC. The study found that the overall survival rate (OS) and progress-free survival rate (rPFS) of patients treated with Lu-177-PSMA-617 improved.
The VISION study included 831 patients who were randomized 2:1 to the treatment group. This open-label trial monitored patients for 6 to 10 months during treatment, allowing physicians to select the best supportive care, except for the study drug, cytotoxic chemotherapy, other systemic radioisotopes, and half-body radiation therapy. Long-term follow-up will collect survival data and treatment updates, and will include monitoring for adverse events and blood tests. The primary endpoints of this study were overall survival (OS) and recurrent progression-free survival (rPFS).
The results presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting showed that, compared with SOC, adding Lu-177-PSMA-617 reduced the risk of death by approximately 40% and improved median overall survival (OS) by 4 months (HR, 0.62; 95% CI, 0.52–0.74; P < .001). For OS, the median was 15.3 months in the Lu-177-PSMA-617 group and 11.3 months in the SOC group.
Researchers also found that radioligand therapy improved rPFS by 5.3 months, equivalent to a 60% reduction in the risk of progression or death (HR, 0.40; 99.2% CI, 0.29–0.57; P < .001). The median rPFS were 8.7 months and 3.4 months, respectively.
The secondary endpoints of the study were statistically significant and favored the Lu-177-PSMA-617 group. The objective remission rate and disease control rate were 29.8%, 1.7%, 89% and 66.7%, respectively.
Although Lu-177-PSMA-617 was well tolerated, some common adverse reactions were fatigue (49.1% vs. 29.3% in the control group), myelosuppression (47.4% vs. 17.6%, respectively), dry mouth (39.3% vs. 1%), nausea/vomiting (39.3% vs. 17.1%), renal effects (8.7% vs. 5.9%), second primary malignancy (2.1% vs. 1%), and intracranial hemorrhage (1.3% vs. 1.5%). There were no treatment-related deaths.
Reminder: Despite the progress made in the treatment of prostate cancer, for mCRPC patients, there is still a very high unmet medical need for new targeted treatment options. Studies have proved that Lu-177-PSMA-617 has the potential to improve the clinical treatment pattern, and it is expected to become a brand new treatment option for this type of patient. It is hoped that this new drug will be approved as soon as possible and will be used in clinical practice as soon as possible for the benefit of more cancer patients.
