Genitourinary Cancers Symposium
Genitourinary Cancers Symposium
February 14, 2019
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Targeted radiation therapy yields high response rates in metastatic prostate cancer

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SAN FRANCISCO — The targeted radiation therapy Lutetium-177 PSMA-617 produced high response rates among men with prostate-specific membrane antigen-positive metastatic, castration-resistant prostate cancer, according to results of a single-arm, phase 2 trial scheduled for presentation at Genitourinary Cancers Symposium.

The treatment also appeared well-tolerated among these men, whose disease had progressed after multiple standard therapies.

“This is a study of cancer that has spread quite widely and is no longer sensitive to standard hormone treatment,” Michael S. Hofman, MD, professor of nuclear medicine at Peter McCallum Cancer Center in Melbourne, Australia, said during a press cast. “There have been major advances in the past few years with several drugs that prolong survival, but the disease remains fatal in a relatively short period of time, and there is an urgent need for more effective treatments.”

Lutetium-177 (177Lu)-PSMA-617 (Endocyte) is a radiolabeled small molecule that selectively binds to prostate-specific membrane antigen (PSMA) — a common receptor on prostate cancer cells — allowing beta-radiation to be delivered directly to tumors.

Researchers previously reported positive responses to 177Lu-PSMA-617 with low toxicity among 30 men with metastatic, castration-resistant prostate cancer. The updated results include an expansion cohort of 20 men, with median follow-up of 23.5 months.

Among all 50 patients (median age, 71 years; range 50-87; median PSA doubling time, 2.6 ng/ml/month; median PSA, 190), most (90%) had previously received abiraterone (Zytiga, Janssen), enzalutamide (Astellas, Pfizer) or both, whereas 84% had received docetaxel and 48% had received cabazitaxel (Jevtana;  Sanofi, Genzyme).

The investigators administered a median four cycles of 177Lu-PSMA-617 every 6 weeks. Eight men received less than four doses of due to a remarkable response, and 10 patients discontinued 177Lu-PSMA-617 because their disease had progressed.

Results showed reductions in PSA of 30% or greater in 37 men (74%; 95% CI, 60-84), including reductions of 50% or more in 32 men (64%; 95% CI, 50-77); and 80% or more in 22 men (44%; 95% CI, 30-59).

Median OS was 13.3 months (95% CI, 10.5-18), which researchers noted is longer than the average 9-month survival among men with disease at this stage. Patients who attained more than a 50% reduction in PSA levels had significantly longer OS than patients who did not (18 months vs. 8.7 months; P = .001).

Median PSA-PFS was 6.9 months (95% CI, 6-8.7).

Fourteen patients who experienced disease progression after the conclusion of the study received additional 177Lu-PSMA-617 (median, two cycles). Nine of these men subsequently showed PSA declines of 50% or more. Median OS among these patients was 33 months.

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The most frequent grade 1 or grade 2 treatment-related toxicities included dry mouth (68%), nausea (48%) and fatigue (36%). Treatment-associated grade 3 to grade 4 toxicities were uncommon and included thrombocytopenia (10%) and anemia (10%).

Two randomized trials, one comparing 177Lu-PSMA-617 with chemotherapy and the other with the standard of care, have been initiated based on these results, according to the researchers.

“The results of this 50-patient study provide further confidence to our 30-patient study demonstrating high response rates and low toxicity in men with metastatic castration-resistant prostate cancer which has progressed after conventional therapies,” Hofman said. – by Jennifer Byrne

Reference:

Hofman MS, et al. Abstract 4210. Presented at: Genitourinary Cancers Symposium; Feb. 14-16, 2019; San Francisco.

Disclosures: Hofman reports a consultant/advisory role with Endocyte, institutional research funding from Endocyte, and expenses for travel and accommodations from Ipsen and Sanofi. Please see the abstract for all other authors’ relevant financial disclosures.