ESMO 2019: Preliminary Results of A Phase I/II Dose-Escalation Study of Fractionated Dose 177Lu-PSMA-617 for Progressive Metastatic Castration Resistant Prostate Cancer - A Medical Oncologist's Perspective

Barcelona, Spain (UroToday.com) Prostate-specific membrane antigen (PSMA) is highly expressed in the vast majority of prostate cancers relative to normal prostate epithelium and other tissues, and is even more highly expressed in more aggressive and advanced prostate cancers. Lutetium is a beta-emitting therapeutic radionuclide with a relatively long half-life that has maximal tissue penetration of less than 2 mm. 177Lu-PSMA-617 consists of a PSMA molecule attached to the therapeutic radionuclide, which is preferentially internalized into prostate cancer cells. At ESMO 2018, Dr. Tagawa and colleagues presented initial phase 1 safety data from dose escalation of this therapeutic modalities, reporting no dose limiting toxicity.

In this poster, Dr. Tagawa and colleagues present results from a phase 1/2 cohort (NCT03042468) of 44 men with mCRPC that had progressed after chemotherapy and either enzalutamide or abiraterone. A subset of the analyzed patients were part of the dose-escalation group, and the rest received the phase 2 radiation dose. There was no selection for PSMA expression prior to cohort inclusion and 177Lu-PSMA-617 treatment. PSMA-PET scans, standard staging imaging, and circulating tumor cell (CTC) counts were obtained before and after treatment. Treatment was administered in a hypofractionated dose of 1 cycle, 2 doses two weeks apart.

The median age of treated men was 59 (range 55-91), and the median PSA was 182.97 (range 0.9-5541). Almost all men had bone metastatic disease, 18% had lung mets, 9% had liver mets, and 9% had other visceral metastatic disease. In total, 82% of patients exhibited some PSA decline and 67% of patients receiving the phase 2 dose had a PSA decline of greater than 50%. At the time of data analysis, the median overall survival was 16 months, and 57.7% of patients with pre- and post-treatment data had a decrease in CTC count. Major side effects were xerostomia (61.4%) reflective of PSMA positivity in salivary glands, fatigue (29.5%), pain flare (25%) and nausea (15.5%). In a multivariate analysis incorporating dose of lutetium, PSMA PET SUVmax, prior chemotherapy, and other factors, the dose administered and maximum PSMA-PET SUV were associated with response to treatment.

Overall, this poster shows that a single fractionate cycle of 177Lu-PSMA-617 is safe and effectively lowers PSA in the majority of patients even without pre-selection for PSMA positivity in tumors. Pre-treatment PSMA PET may still prove to be important in choosing patients most likely to respond to therapy.

Presented by: Scott Tagawa, MD, Medical Oncologist and Medical Director of Genitourinary Oncology research at Weill Cornell Medical Center, New York, New York