Posted: Friday, March 10, 2023
According to Scott T. Tagawa, MD, MS, of Weill Cornell Medicine, New York, and colleagues, the prostate-specific membrane antigen (PSMA)-targeted monoclonal antibody J591 seemed to improve metastasis-free survival outcomes when radiolabeled with lutetium-177 (Lu-177) versus indium-111 (In-111) in patients with high-risk nonmetastatic castration-resistant prostate cancer who received ketoconazole and hydrocortisone. The results of this phase II study, which were presented during the 2023 American Society for Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium (Abstract LBA21), support the development of anti-PSMA radioimmunotherapy for low-volume advanced disease.
“PSMA is expressed on most prostate cancers and can be targeted by radiolabeled J591,” the investigators remarked. “Hormonal therapy is effective and may increase PSMA expression and radiosensitize.”
A total of 55 patients who were administered ketoconazole and hydrocortisone for a minimum of 4 weeks as lead-in therapy were randomly assigned in a 2:1 ratio to receive a single infusion of J591 labeled with either Lu-177 or In-111. The intention-to-treat analysis revealed an 18-month metastasis rate of 50% with Lu-177 and 76% with In-111 (P = .066). Based on analyses censoring the start of new treatment, the median durations of metastasis-free and biochemical progression–free survival were 23.8 and 18.7 months with Lu-177 and 20.8 and 8.9 months with In-111, respectively. Confirmed prostate-specific antigen declines of more than 50% occurred in 82% of the Lu-177 arm versus 71% of the In-111 arm.
Hematologic adverse events higher than grade 3, such as neutropenia (57% vs. 11%) and thrombocytopenia (77% vs. 11%; platelet transfusions: 25% vs. 6%), were reported more frequently with Lu-177. However, labeling with this radiometal resulted in fewer nonhematologic adverse events higher than grade 3, such as abdominal pain (0% vs. 11%), increased alanine transaminase levels (3% vs. 22%), and diarrhea (0% vs. 22%).
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
2023 ASCO GU Cancers Symposium