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- Title
Circulating androgen receptor gene amplification and resistance to <sup>177</sup>Lu-PSMA-617 in metastatic castration-resistant prostate cancer: results of a Phase 2 trial.
- Authors
De Giorgi, Ugo; Sansovini, Maddalena; Severi, Stefano; Nicolini, Silvia; Monti, Manuela; Gurioli, Giorgia; Foca, Flavia; Casadei, Chiara; Conteduca, Vincenza; Celli, Monica; Di Iorio, Valentina; Calistri, Daniele; Matteucci, Federica; von Eyben, Finn Edler; Attard, Gerhardt; Paganelli, Giovanni
- Abstract
<bold>Background: </bold>In a Phase 2 clinical trial, we aimed to determine the lutetium-177 [177Lu]-PSMA-617 activity and the clinical utility of levels of plasma androgen receptor (AR) gene in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC).<bold>Methods: </bold>We determined AR copy number in pretreatment plasma samples. We used logistic regression to estimate the odds ratio (OR) and 95% confidence intervals (95% CIs) in order to evaluate the independent relevance of AR status and to evaluate patients with early progressive disease (PD) defined as treatment interruption occurring within 4 months after the start of 177Lu-PSMA-617.<bold>Results: </bold>Twelve of the 15 (80%) with AR gene gain and 5 of the 25 (20%) patients with no gain of AR had early PD (p = 0.0002). The OR for patients without PSA response having AR gain was 3.69 (95% CI 0.83-16.36, p = 0.085). The OR for patients with early PD having AR gain was 16.00, (95% CI 3.23-79.27, p = 0.0007). Overall, median PFS and OS were 7.5 and 12.4 months, respectively. AR-gained had a significant shorter OS compared to AR-normal patients (7.4 vs 19.1 months, p = 0.020). No treatment interruptions due to adverse effects were reported.<bold>Discussion: </bold>Plasma AR status helped to indicate mCRPC with early resistance to 177Lu-PSMA-617.<bold>Trial Registration: </bold>NCT03454750.
- Publication
British Journal of Cancer, 2021, Vol 125, Issue 9, p1226
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/s41416-021-01508-5