Serum biomarkers in metastatic castration-resistant prostate cancer (mCRPC) patients receiving [ <sup>177</sup> Lu]Lu-PSMA-617 therapy: Post hoc analysis of a phase II clinical trial.
Abstract
190 Background: [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) has been recently approved for metastatic castration-resistant prostate cancer (mCRPC). Several clinical trials have assessed the efficacy of 177 Lu-PSMA-617, but only half of the eligible patients seem to obtain a clear benefit from it. Currently, there is a lack of validated biomarkers that could help find the best candidates for this radioligand therapy. Methods: In the IRST185.03, a single-arm monocentric phase II clinical trial, 142 mCRPC patients received 177 Lu-PSMA-617 at a dose of 3.7-5.5 Gbq every 8-12 weeks for a maximum of 4 cycles. Baseline blood samples were collected within 7 days from the first dose of 177 Lu-PSMA-617. Hemoglobin (Hb), alkaline phosphatase (ALP), prostate-specific antigen (PSA), carcinoembryonic Antigen (CEA), chromogranin A (CgA), and neuron-specific Enolase (NSE), as well as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), were analyzed at both uni- and multivariate levels to evaluate their correlation to progression-free survival (PFS). Results: At the time of data cut-off, after a median follow-up time of 44.0 months, the median PFS in the global cohort was 7.0 months. At univariate analysis, among serum biomarkers, lower PLR (cut-off: 210, HR: 0.66, 95% CI: 0.44-0.99, p=0.04), lower ALP (cut-off: upper limit of normal, HR: 0.51, 95% CI: 0.34-0.75, p<0.01), lower PSA (cut-off: median value, HR: 0.51, 95% CI: 0.35-0.74, p<0.01), and lower CEA (cut-off: upper limit of normal, HR: 0.55, 95% CI: 0.32-0.95, p=0.03) were associated with longer PFS. Among clinical characteristics, the previous use of docetaxel (HR: 1.48, 95% CI: 1.04-2.10, p=0.03) was associated with shorter PFS. At multivariate analysis, only PSA and CEA remained prognostic for PFS (p=0.01 and 0.02. respectively). Conclusions: High PSA and CEA levels appeared the only serum predictors of poor clinical outcome to 177 Lu-PSMA-617 therapy in mCRPC. The role of CEA as potential biomarker associated with 177 Lu-PSMA-617 needs to be confirmed since it could be linked to aggressive prostate cancer variant. Clinical trial information: 2016-002732-32 .
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (17)
Emilio Francesco Giunta
Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori,” IRCCS, Meldola, Italy
Irene Marini
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Anna Sarnelli
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Nicole Brighi
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Flavia Foca
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Giuseppe Schepisi
Milena Urbini, PhD, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy; Thomas F. Eleveld, PhD, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Maurizio Polano, PhD, Experimental and Clinical Pharmacology Unit, IRCCS Centro di Riferimento Oncologico di Aviano (CRO), Aviano, Italy; Emanuela Scarpi, PhD, Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy; Cecilia Menna, MD, and Caterina Gianni, MD, Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy; Ferdinand W. Janssen, MSc, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Giuseppe Schepisi, MD, Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy; Giorgia Gurioli, PhD, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei ...
Cristian Lolli
Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
Manuela Monti
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Silvia Nicolini
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Maria Concetta Cursano
Giovanni Rosti
Milena Urbini, PhD, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy; Thomas F. Eleveld, PhD, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Maurizio Polano, PhD, Experimental and Clinical Pharmacology Unit, IRCCS Centro di Riferimento Oncologico di Aviano (CRO), Aviano, Italy; Emanuela Scarpi, PhD, Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy; Cecilia Menna, MD, and Caterina Gianni, MD, Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy; Ferdinand W. Janssen, MSc, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Giuseppe Schepisi, MD, Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy; Giorgia Gurioli, PhD, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei ...
Ilaria Grassi
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Giovanni Paganelli
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Stefano Severi
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Federica Matteucci
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Maddalena Sansovini
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Ugo De Giorgi
Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori, Meldola, Italy