Survival with novel hormonal therapies in patients with nonmetastatic castration-resistant prostate cancer: indirect comparison of three randomized phase-III trials.

In recent years, new treatments have been approved for nonmetastatic castration-resistant prostate cancer (M0CRPC). Because direct comparisons between these treatments are not available to guide treatment decisions, indirect comparisons can be of interest.

Our analysis evaluated second-generation hormone treatments proposed for M0CRPC. We searched multiple databases for articles published between 2010 and 2022. Phase-III clinical trials that studied these agents in M0CRPC patients were eligible. Among these, we included trials reporting overall survival (OS) through Kaplan-Meier curves. We performed the reconstruction of individual patient data from Kaplan-Meier graphs, according to the Shiny method, to indirectly compare the efficacy of the different agents. Indirect comparisons included testing for equivalence according to FDA criteria. Confidence intervals (CI) were 95% in all analyses except equivalence testing, where 90%CIs were used.

Three studies met these inclusion criteria. Apalutamide (hazard ratio [HR]: 0.75, 95% confidence interval [CI] 0.64-0.88), darolutamide (HR 0.70, 95%CI 0.58-0.84), and enzalutamide (HR 0.77, 95%CI 0.65-0.90) were all significantly more effective than the placebo. Our results showed no difference in OS between any of these three agents, and in testing for equivalence, our estimates of HR met the 0.75-1.33 level.

While the Shiny method has confirmed its validity in reconstructing individual patient data, our indirect comparisons based on mature OS demonstrated similar efficacy and substantial equivalence among these three second-generation androgen receptor inhibitors.

World journal of urology. 2022 Sep 09 [Epub ahead of print]

Melania Rivano, Luca Cancanelli, Lorenzo Di Spazio, Daniele Mengato, Marco Chiumente, Andrea Messori

Hospital Pharmacy Department, Binaghi Hospital, Via Is Guadazzonis, 2, 09126, Cagliari, Italy., Hospital Pharmacy Department, Azienda Ulss 2 Marca Trevigiana, Via Ospedale, 16, Castelfranco Veneto, 31033, Treviso, Italy., Hospital Pharmacy Department, S.Chiara Hospital, Largo Medaglie d'oro, 38122, Trento, Italy., Hospital Pharmacy Department, Azienda Ospedale - Università of Padova, via Giustiniani 2, 35128, Padua, Italy., Direzione Scientifica, Società Italiana Di Farmacia Clinica E Terapia (SIFaCT), Milan, Italia., HTA Unit, Regione Toscana, via Alderotti 26/N, 50135, Florence, Italy. .

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