Investigational Therapy Significantly Improves Survival in Patients with Prostate Cancer

Treatment with the investigational targeted radioligand therapy ¹⁷⁷Lu-PSMA-617 (LuPSMA) and standard of care induced a nearly 40% reduction in the risk of death versus standard of care alone in patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC), according to data from the phase 3 VISION trial.

The findings, which were presented during a presscast held before the 2021 ASCO Annual Meeting, showed that at a median follow-up of 20.9 months, the addition of LuPSMA improved the median overall survival (time that a patient with cancer is still alive) by four months over standard of care alone. Adding the targeted radioligand therapy also led to a 5.3-month improvement in median radiographic progression-free survival (time from randomization to first evidence of radiographic disease progression or death), translating to a 60% reduction in the risk of progression or death (HR, 0.40).

“These findings warrant adoption of LuPSMA as a new treatment option in patients with mCRPC, pending (Food and Drug Administration) approval,” said lead VISION trial author Dr. Michael J. Morris, head of the Prostate Cancer Section at Memorial Sloan Kettering Cancer Center in New York.

The trial included 831 patients with progressive PSMA-positive mCRPC who received at least one novel androgen axis drug (eg, Xtandi [enzalutamide] or Zytiga [abiraterone acetate]) and were previously treated with one to two taxane regimens.

Patients were randomized to receive LuPSMA plus standard of care (551 patients) or standard of care alone (280 patients). Individual investigators determined what the standard of care would be; however, treatment with Xofigo (radium-223) and cytotoxic chemotherapy were not allowed. Measuring overall survival and radiographic progression-free survival were the main goals of the study.

LuPSMA is described, by it’s manufacturer Novartis, as a precision cancer treatment that combines a targeting compound with a particular radioactive particle. Once administered, the therapy binds to prostate cancer cells that express a certain protein. The treatment then damages tumor cells, which help disrupt their ability to replicate and/or trigger cell death, according to Novartis.

Patients who received LuPSMA plus standard of care achieved a median overall survival of 15.3 months compared with 11.3 months in those who received standard of care alone, translating to a 38% reduction in the risk of death. Moreover, radiographic progression-free survival was 8.7 versus 3.4 months, respectively.

There was also a statistically significant benefit favoring the LuPSMA treatment group for other outcomes including, but not limited to, objective response rate (the percentage of patients with partial and complete responses to the treatment).

The safety analysis included 529 patients in the LuPSMA treatment group and 205 patients in the standard-of-care treatment group. The investigators considered LuPSMA treatment to be well tolerated. The most common side effects occurring in the LuPSMA group were fatigue (49.1% vs. 29.3% in the standard of care alone group), bone marrow suppression (47.4% vs. 17.6%, respectively), dry mouth (39.3% vs. 1%), nausea/vomiting (39.3% vs. 17.1%), kidney effects (8.7% vs. 5.9%), second primary malignancies (2.1% vs. 1%), and intracranial bleeding (1.3% vs. 1.5%).

Serious or severe treatment-emergent side effects occurred in 52.7% of patients receiving LuPSMA compared with 38% of patients treated with standard of care alone.

Regarding the next steps with LuPSMA, Morris said, “There are ongoing trials of LuPSMA in patients with prostate cancer at earlier phases of the disease.”

Commenting on the significance of the VISION study results, ASCO President Dr. Lori J. Pierce said, “This is an important study, as the patients in this trial had mCRPC, so they had disease that grew even when testosterone in the body had already been reduced to very low levels, despite receiving one to two prior taxane regimens.”

She added, “This trial shows an alternative to traditional therapies by using radiation targeted to the PSMA antigen. So, it could be delivered directly to the prostate cancer cells, and by doing that, survival was significantly improved. Use of the PSMA radioligand therapy, if it obtains regulatory approval, could indeed become an important treatment option for these patients with refractory disease.”

There are currently two PSMA PET imaging agents approved for patients with prostate cancer, Ga 68 PSMA-11 and Pylarify (18F-DCFPyL). Novartis plans to file for FDA approval of the radioligand therapy based on these positive findings from the VISION trial. If approved, LuPSMA would become the first PSMA theranostic approved in prostate cancer.

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