Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer
Mario Campone, Michelino De Laurentiis, Komal Jhaveri, Xichun Hu, Sylvain Ladoire, Anne Patsouris, Claudio Zamagni, Jiuwei Cui, Marina Elena Cazzaniga, Timuçin Çil, Katarzyna J. Jerzak, C.S. Fuentes, Tetsuhiro Yoshinami, Álvaro Rodríguez-Lescure, Ahmet Sezer, Andrea Fontana, Valentina Guarneri, Andrea Molckovsky, Marie‐Ange Mouret‐Reynier, Umut Demırcı, Yongqiang Zhang, Olga Valota, Dongrui R. Lu, Marcella Martignoni, Janaki Parameswaran, Xin Zhi, Erika Hamilton
Abstract
BACKGROUND: Vepdegestrant is an oral proteolysis-targeting chimera (PROTAC) estrogen receptor (ER) degrader that directly harnesses the ubiquitin-proteasome system. METHODS: mutations and among all the patients who underwent randomization. Progression-free survival was estimated with Kaplan-Meier methods and hazard ratios with a stratified Cox proportional-hazards model. RESULTS: mutations, the median progression-free survival was 5.0 months (95% confidence interval [CI], 3.7 to 7.4) with vepdegestrant and 2.1 months (95% CI, 1.9 to 3.5) with fulvestrant (hazard ratio, 0.58 [95% CI, 0.43 to 0.78]; P<0.001). Among all the patients, the median progression-free survival was 3.8 months (95% CI, 3.7 to 5.3) with vepdegestrant and 3.6 months (95% CI, 2.6 to 4.0) with fulvestrant (hazard ratio, 0.83 [95% CI, 0.69 to 1.01]; P = 0.07). Adverse events of grade 3 or higher occurred in 23.4% of the patients in the vepdegestrant group and in 17.6% of the patients in the fulvestrant group. Adverse events led to treatment discontinuation in 2.9% and 0.7% of the patients, respectively. CONCLUSIONS: mutations but not in the full patient population. (Funded by Pfizer and Arvinas Estrogen Receptor; VERITAC-2 ClinicalTrials.gov number, NCT05654623.).