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Phase II Study of Lutetium-177–Labeled Anti-Prostate-Specific Membrane Antigen Monoclonal Antibody J591 for Metastatic Castration-Resistant Prostate Cancer

2013; American Association for Cancer Research; Volume: 19; Issue: 18 Linguagem: Inglês

10.1158/1078-0432.ccr-13-0231

1557-3265

Scott T. Tagawa, Matthew I. Milowsky, Michael J. Morris, Shankar Vallabhajosula, Paul J. Christos, Naveed Akhtar, Joseph R. Osborne, Stanley J. Goldsmith, Steven M. Larson, Neeta Pandit Taskar, Howard I. Scher, Neil H. Bander, David M. Nanus,

Peptidase Inhibition and Analysis

Abstract Purpose: To assess the efficacy of a single infusion of radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (lutetium-177; 177Lu) by prostate-specific antigen (PSA) decline, measurable disease response, and survival. Experimental Design: In this dual-center phase II study, two cohorts with progressive metastatic castration-resistant prostate cancer received one dose of 177Lu-J591 (15 patients at 65 mCi/m2, 17 at 70 mCi/m2) with radionuclide imaging. Expansion cohort (n = 15) received 70 mCi/m2 to verify response rate and examine biomarkers. Results: Forty-seven patients who progressed after hormonal therapies (55.3% also received prior chemotherapy) received 177Lu-J591. A total of 10.6% experienced ≥50% decline in PSA, 36.2% experienced ≥30% decline, and 59.6% experienced any PSA decline following their single treatment. One of 12 with measurable disease experienced a partial radiographic response (8 with stable disease). Sites of prostate cancer metastases were targeted in 44 of 47 (93.6%) as determined by planar imaging. All experienced reversible hematologic toxicity, with grade 4 thrombocytopenia occurring in 46.8% (29.8% received platelet transfusions) without significant hemorrhage. A total of 25.5% experienced grade 4 neutropenia, with one episode of febrile neutropenia. The phase I maximum tolerated dose (70 mCi/m2) resulted in more 30% PSA declines (46.9% vs. 13.3%, P = 0.048) and longer survival (21.8 vs. 11.9 months, P = 0.03), but also more grade 4 hematologic toxicity and platelet transfusions. No serious nonhematologic toxicity occurred. Those with poor PSMA imaging were less likely to respond. Conclusion: A single dose of 177Lu-J591 was well tolerated with reversible myelosuppression. Accurate tumor targeting and PSA responses were seen with evidence of dose response. Imaging biomarkers seem promising. Clin Cancer Res; 19(18); 5182–91. ©2013 AACR.