Experimental Therapy Shows Promise in Metastatic Castration-Resistant Prostate Cancer

An experimental molecular radiopharmaceutical, ¹⁷⁷Lu-PSMA-617 (LuPSMA), appeared to be more active than the chemotherapy drug Jevtana (cabazitaxel) in patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease progressed after receiving treatment with the chemotherapy docetaxel, according to data from the TheraP trial presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.

The data also demonstrated that grade 3 or 4 side effects, which are considered serious or severe, were less common in patients who received LuPSMA.

“LuPSMA is a novel class of therapy with high activity and relatively low toxicity, consistent with the results of prior single-center studies in phase 2 data,” Dr. Michael S. Hofman, of the Peter MacCallum Cancer Center in Australia, said during a presentation of the data. “On the basis of these results, (LuPSMA) appears to represent a new class of effective therapy for men with metastatic castration-resistant prostate cancer.”

This form of the disease has spread beyond the prostate to distant parts of the body and has stopped responding to previous treatments.

LuPSMA, a small molecule that bonds to prostate-specific membrane antigen (a cell-surface glycoprotein that is overexpressed in metastatic prostate cancer) enables delivery of high doses of radiation to sites affected by prostate cancer. This delivery method results in high tumor targeting, but also limits damage to the surrounding tissue.

Patients were included in the randomized phase 2 trial if their cancer had progressed after treatment with docetaxel and they were deemed suitable for Jevtana. To be eligible, patients also had to have progressive disease with rising prostate-specific antigen (PSA), a protein associated with the presence of prostate cancer, and their PSA level had to be equal to or greater than 20 nanograms (ng) per milliliter (mL).

Study participants were divided into groups to receive either LuPSMA (99 patients) or Jevtana (101 patients). Men in the experimental arm underwent SPECT/CT imaging after each cycle of LuPSMA, and if an exceptional response was demonstrated, their treatment was paused, and they could resume treatment when their PSA levels progressed.

The main outcome of the study was PSA response rate, which was defined by a 50% or greater reduction in PSA levels. Additional outcomes of the study included PSA-progression-free survival (PFS), meaning the amount of time from the start of treatment until PSA increased; side effects; and overall survival (OS), or the length of time from the start of treatment until death.

Of note, 17 patients, 16 of whom were randomized to receive Jevtana, withdrew or died prior to beginning treatment on the study.

Patients who received LuPSMA achieved a higher PSA response rate (66%) than those who received Jevtana (37%), which represents a 29% absolute greater PSA response rate. However, in a sensitivity analysis, the difference the investigators observed was 23%.

At a median follow-up of 13.3 months, LuPSMA was shown to have significantly improved PSA-PFS. There have been 71 deaths in total, a number that is not yet analyzable, according to Hofman; additional follow-up is needed to assess overall survival.

“Importantly, improvements in overall survival have not yet been demonstrated, and we eagerly await the results of the upcoming phase 3 VISION trial,” Hofman said.

Thirty-six percent of the men who received LuPSMA reported experiencing grade 3 or 4 side effects, compared with 49% of the patients who received Jevtana. More patients within the LuPSMA arm (11) died compared with those in the Jevtana arm (5), but the investigators noted that none of the deaths were related to treatment.

A version of this story originally appeared on OncLive® as “Phase II TheraP Trial Shows Promise for LuPSMA in mCRPC”.