postate-cancer

Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer

Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer

Background on purpose

Therapeutic options for patients with metastatic castration resistant prostate cancer remain limited.  Many of these patients die of their disease rather than die with their disease.  In recent years prostate-specific membrane antigen has become a popular therapeutic target.  It is highly expressed in metastatic castration resistant prostate cancer cells.  Lutetium 177–PSMA–617 is a radiopharmaceutical that delivers beta particles to PSMA expressing cells as well as the local environment. 

Methods

An international, open label, phase 3 clinical trial was performed, evaluating Lutetium 177–PSMA–617 in patients with metastatic castration resistant prostate cancer.  These patients had been previously treated with at least 1 androgen receptor pathway inhibitor and 1 or 2 taxane agents.  Patients were required to have PSMA positive gallium-68 labeled PSMA-11 positron emission tomographic computed tomographic scans.  Patients were randomly assigned in a 2:1 ratio.  They were randomized to receive either Lutetium 177–PSMA–617 at 7.4 GBq every 6 weeks for 4-6 cycles plus protocol permitted standard of care alone or SOC alone.  Protocol permitted standard care excluded chemotherapy, immunotherapy, radium-223 and investigational agents.  Alternate primary endpoints were imaging based progression free survival as well as overall survival.  These were powered by hazard ratios of 0.67 and 0.73, respectively.  Important secondary endpoints included objective response, time to symptomatic skeletal events, and disease control rate.  Adverse events had to have occurred within 30 days of discontinuation of therapy.

Results

 831 out of 1179 screen patients underwent randomization. baseline patient characteristics were well balanced. the median follow-up was 20.9 months. Lutetium 177–PSMA–617 plus standard care significantly prolonged both imaging based progression free survival, median, 8.7 versus 3.4 months, hazard ratio for progression or death, 0.40, 99.2% confidence interval, 0.29–0.57, P < 0.001 and overall survival, median, 15.3 versus 11.3 months, hazard ratio for death, 0.62, 95% confidence interval 0.52–0.74, P < 0.001 versus control. All secondary endpoints significantly favored Lutetium 177–PSMA–617. The incidence of adverse events from grade 3 or above was higher with Lutetium 177–PSMA–617 then without, 52.7% versus 38%, but quality of life was not adversely affected.

Conclusion

the authors concluded “radioligand therapy with Lutetium 177–PSMA–617 prolonged imaging based progression free survival and overall survival when added to standard care in patients with advanced PSMA positive metastatic castration resistant prostate cancer.

Reference:

Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer

https://www.nejm.org/doi/full/10.1056/NEJMoa2107322

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