Triplet Therapy in Metastatic Hormone-Sensitive Prostate Cancer—Calling Out the “Double Standard”

A partir d'une revue systématique de la littérature publiée jusqu'en juin 2021 (10 essais cliniques incluant au total 11 043 patients), cette méta-analyse en réseau compare l'intérêt, du point de vue de la survie sans progression, de la survie globale, de la survenue d'événements secondaires de grade 3 ou plus et de la qualité de vie, de différentes options de traitements systémiques de première ligne chez les patients atteints d'un cancer métastatique de la prostate sensible à la castration

Résumé en anglais

The gold standard for treating metastatic hormone-sensitive prostate cancer (mHSPC) has evolved rapidly in the past decade based on completed phase 3 randomized clinical trials (RCTs) of doublets showing that androgen deprivation therapy (ADT) in combination with docetaxel (ADT-D), reported first in the CHAARTED trial, and later with multiple androgen-receptor signaling inhibitors (ARSIs) were superior to ADT alone in improving the time to progression and prolonging life. More recently, the PEACE-1 and ARASENS trials showed a similar overall survival (OS) benefit with a triplet regimen of ADT, docetaxel, and either abiraterone (ADT-D-AA) or darolutamide (ADT-D-Daro), the latter drug first approved by the US Food and Drug Administration for nonmetastatic castration-resistant disease. In both trials, the triplet was superior to ADT-D, with ADT-D-Daro established as an US Food and Drug Administration–approved standard of care for mHSPC. Not formally studied was whether the triplet regimen confers a similar progression-free survival and OS advantage to an ADT-ARSI doublet, the more broadly used treatment in contemporary practice due to a more favorable safety profile and ease of administration.