At the ESMO 2018 Conference that was recently concluded, there was a report of the clinical experience of 100 men with metastatic castrate resistant prostate cancer (mCRPC) who were consecutively treated with Lu-177 PSMA-I&T Radioligand Therapy. The therapy uses the prostate-specific membrane antigen (PSMA) which shows increased activity in prostate cancer cells that are androgen independent for targeting a radioactive treatment, Lutetium-177 (177Lu)-PSMA617 (LuPSMA).
PSMA is over-expressed in all prostate tissue, including prostatic cancer. The Lutetium-177 is a small radiolabeled molecule which binds to the PSMA and delivers a dose of radiation. Lutetium-177 delivers short range β radiation (maximal tissue penetration of <2mm), thereby decreasing the potential collateral damage to nearby organs including the bone marrow.
This study presented at the ESMO Conference describes the clinical experience of 100 men treated who were treated with 177Lu-PSMA. Regarding baseline characteristics, the median age was 72, and median PSA was 175. This cohort was a heavily pretreated population of men with 57% of them have already had 3 or more prior therapy. Pretreatment experiences included 82% of them having had chemotherapy. Overall, this was a cohort of men with very aggressive disease.
Eleven percent (11%) of the men had a >90% PSA decline, with 38% achieving 50% PSA decline and 47% reaching 30% PSA decline. The median clinical progression-free survival was 4.1 months, and overall survival was 12.9 months.
A PSA decline by 50% or more was associated with longer clinical progression-free survival and overall survival (OS). Those men who had a PSA decline of 50% or more had a median OS of 10.8 months, compared to 2.9 months for those who had a lesser PSA decline.
Toxicities were tolerable with no grade 3 or 4 non-hematologic toxicities, and the most common grade 3 or 4 hematologic toxicities were anemia (9%), thrombocytopenia (4%) and neutropenia (6%). Dry mouth is the most common non-hematologic toxicity.
The study authors concluded that 177Lu-PSMA appears to be a safe and active therapy for men with mCRPC who have been heavily pretreated. The PSA response, progression-free survival, and overall survival appear similar to that of cabazitaxel (Jevtana) treatment for men who progressed on docetaxel. However, the toxicity profile is noticeably lower with 177Lu-PSMA – grade 3 or higher neutropenia was present in almost all men (82%) with cabazitaxel compared to only 6% for 177Lu-PSMA. Also, 177Lu-PSMA had no grade 3 or 4 non-hematologic toxicities, but men with cabazitaxel had several grades 3 or higher toxicities.
By Joel T Nowak, MA, MSW