Novel radiation therapy promising for metastatic castration-resistant prostate cancer

By Megan Brooks

NEW YORK (Reuters Health) - 14/2/2019

A novel, targeted radiation therapy called Lutetium-177 PSMA-617 (LuPSMA) has shown promising clinical activity in men with prostate-specific membrane antigen (PSMA)-positive metastatic, castration-resistant prostate cancer (mCRPC) that progressed despite multiple standard therapies.

"LuPSMA provides a new approach to a form of the disease that has been difficult to treat," lead study investigator Dr. Michael Hofman of the Peter MacCallum Cancer Centre, in Melbourne, Australia, said in a news release.

He discussed the findings of a new phase 2 trial during a press briefing February 11 in advance of presentation February 14 in San Francisco at the Genitourinary Cancers Symposium, co-sponsored by the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology and the Society of Surgical Oncology.

"PSMA is over-expressed 100 to 1000 times in prostate cancers, with expression further increased in metastatic and castration-resistant carcinomas," Dr. Hofman explained during the briefing. LuPSMA is a radiolabeled small molecule that binds with high affinity to PSMA, allowing tumor-targeted delivery of beta-radiation.

The trial enrolled 50 men (median age, 71) with mCRPC and PSMA expression on tumor cells determined by positron emission tomography (PET). Most had previously been treated with docetaxel or antiandrogen therapy (abiraterone and/or enzalutamide) and close to half had also received second-line cabazitaxel chemotherapy. Treatment consisted of up to four intravenous cycles of LuPSMA every six weeks.

Thirty-two of the 50 men (64%) had at least a 50% decline in PSA after treatment with LuPSMA and 22 (44%) had at least an 80% decline in PSA, Dr. Hofman reported.

Median overall survival for the cohort was 13.3 months, while the average survival time in this patient population is six to nine months. Survival time was significantly longer in patients with at least 50% decline in PSA (18.0 months vs. 8.7 months with less than 50% decline in PSA).

Among men who responded to LuPSMA, PSA values remained stable for a median of 6.9 months, indicating that the disease was not progressing.

Fourteen of the men who had disease progression were treated with a median of two more cycles of LuPSMA. In nine of these men, PSA subsequently declined 50% or more and survival in this group of men was 33 months, Dr. Hofman reported.

The most common grade 1 or 2 treatment-related side effects were dry mouth (68%), nausea (48%) and fatigue (36%). The most common grade 3 or 4 side effects were thrombocytopenia and anemia, each occurring in 10% of patients.

Dr. Hofman said the new results "provide further confidence" in previously published data on 30 patients, "demonstrating high response rates and low toxicity in men with mCRPC who progressed after conventional therapies. The high response rates in patients who have failed multiple lines of therapy support a novel mechanism of action for this therapy."

"We have made important progress in treating genitourinary cancers and (LuPSMA) is an intriguing agent," commented ASCO expert and briefing moderator Dr. Robert Dreicer. For patients with mCRPC, "in dire need of new options, using an entirely new approach, this study provides hope that we can start to change their outcomes,” he said.

Based on these early results, two randomized trials of LuPSMA in men with PSMA-positive, progressive mCRPC have been launched. The phase 2 TheraP trial (NCT03392428) is comparing LuPSMA with cabazitaxel and the phase 3 VISION trial (NCT03511664) is testing LuPSMA against best standard of care.

The trial was sponsored by the Peter MacCallum Cancer Centre. PSMA-617 was supplied by Endocyte and Lutetium-177 by ANSTO. Dr. Hofman is a consultant and advisor for Endocyte.

SOURCE: Genitourinary Cancers Symposium 2019

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