| Contributors: |
N. C., Turner; M., Oliveira; S. J., Howell; F., Dalenc; J., Corte; H. L., Gomez Moreno; X., Hu; K., Jhaveri; P., Krivorotko; S., Loibl; S., Morales Murillo; M., Okera; Y. H., Park; J., Sohn; M., Toi; E., Tokunaga; S., Yousef; L., Zhukova; E. C., De Bruin; L., Grinsted; G., Schiavon; A., Foxley; CAPItello-291 Study Group: Luis Enrique Fein, Rugo H. S.; Lucas Kaen, Diego; Dario Kowalyszyn, Ruben; Varela, Mirta; Luis Lerzo, Guillermo; Wong, Vanessa; M Boyle, France; Fox, Peter; Kannourakis, George; Mccarthy, Nicole; Murray, Nichola; Okera, Meena; van der Westhuizen, Andre; Bae, Susie; Goodwin, Annabel; Morris, Michelle; Quaghebeur, Claire; Canon, Jean-Luc; Dirix, Luc; Duhoux, Francoi; Fontaine, Christel; Papadimitriou, Konstantino; Mates, Mihaela; Niraula, Saroj; C Pezo, Rossanna; Puchyr, Martina; Linda Yu, Joanne; Wu, Xinhong; Chen, Wenyan; Pang, Danmei; Zang, Aimin; Wang, Jingfen; Jiang, Ou; Wu, Zhiyong; Dalenc, Florence; Stefani, Laetitia; Luporsi, Elisabeth; Petit, Thierry; Hardy-Bessard, Anne-Claire; Peron, Julien; Monceau-Baroux, Lucie; Meynard, Guillaume; Christophe Thery, Jean; Harbeck, Nadia; Tio, Joke; Schneeweiss, Andrea; Wuelfing, Pia; Schem, Christian; Tesch, Han; A Fasching, Peter; Park-Simon, Tjoung-Won; Reinisch, Mattea; Wimberger, Pauline; Braun, Michael; Hegewisch-Becker, Susanna; Witzel, Isabell; Lux, Michael; Van Mackelenbergh, Marion; Wiebke Fischer, Dorothea; Fischer, Holger; Marmé, Frederik; Griesshammer, Martin; B Al-Farhat, Yousuf; Arkosy, Peter; Csoszi, Tibor; Papai, Zsuzsanna; Laszlo Rubovszky, Gabor; Horvath, Zsolt; Peretz, Tamar; Drumea, Karen; Lubovsky, Shlomit; Itay, Amit; Kuchuk, Iryna; Yerushalmi, Rinat; Yousef, Samih; Kornev, Gleb; Goldvaser, Hadar; Tokar, Margarita |
| Description: |
BACKGROUNDAKT pathway activation is implicated in endocrine-therapy resistance. Data on the efficacy and safety of the AKT inhibitor capivasertib, as an addition to fulvestrant therapy, in patients with hormone receptor-positive advanced breast cancer are limited.METHODSIn a phase 3, randomized, double-blind trial, we enrolled eligible pre-, peri-, and postmenopausal women and men with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer who had had a relapse or disease progression during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy. Patients were randomly assigned in a 1:1 ratio to receive capivasertib plus fulvestrant or placebo plus fulvestrant. The dual primary end point was investigator-assessed progression-free survival assessed both in the overall population and among patients with AKT pathway-altered (PIK3CA, AKT1, or PTEN) tumors. Safety was assessed.RESULTSOverall, 708 patients underwent randomization; 289 patients (40.8%) had AKT pathway alterations, and 489 (69.1%) had received a CDK4/6 inhibitor previously for advanced breast cancer. In the overall population, the median progression-free survival was 7.2 months in the capivasertib-fulvestrant group, as compared with 3.6 months in the placebo-fulvestrant group (hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.51 to 0.71; P |