Overall survival in patients with HR+/HER2- advanced or metastatic breast cancer treated with a cyclin-dependent kinase 4/6 inhibitor plus an aromatase inhibitor: A US Food and Drug Administration pooled analysis.

Abstract

1055 Background: Cyclin-dependent kinase 4/6 inhibitors (CDKI) are FDA-approved for use in combination with aromatase inhibitors (AI) for the treatment of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced or metastatic breast cancer (MBC) as initial (1L) endocrine-based therapy. We have previously reported the pooled analyses of the benefit in progression-free survival of adding CDKI to AI, and here report the pooled overall survival (OS) results for adults treated with CDKI + AI for 1L HR+/HER2- MBC. Methods: We pooled individual patient data (N=2252) from 4 randomized trials (MONALEESA-2 & 7, MONARCH-3, PALOMA-2) of a CDKI (abemaciclib, palbociclib, ribociclib) or placebo + AI in adults with 1L HR+/HER2- MBC. OS was defined as time from randomization to death from any cause and was a key secondary endpoint in all 4 trials. Not all 4 trials reached OS statistical significance, but all OS hazard ratios of the individual trials were <1. The median OS was estimated using Kaplan-Meier methods, and hazard ratios with 95% confidence intervals (CI) were estimated using Cox regression models. Analyses were prespecified, with patients analyzed collectively and by various clinicopathological subgroups of interest. Results: Overall results in all patients and various clinicopathologic subgroups of interest are shown (Table). Conclusions: In this descriptive exploratory pooled analysis, the addition of a CDKI to AI suggested an association with an OS benefit for this class of drugs used as a component of 1L endocrine-based therapy for adults with HR+/HER2- MBC. Additional research is needed to determine which subgroup of patients may benefit more or less of the addition of a CDKI to AI. n # Events CDKI/n (%) # Events Placebo/n (%) HR (95% CI) All 2252 716/1320 (54) 550/932 (59) 0.81 (0.73, 0.91) PR negative 273 84/155 (54) 89/118 (75) 0.51 (0.38, 0.70) De Novo 752 233/450 (52) 173/302 (57) 0.82 (0.67, 1.00) Lobular Histology 144 72/97 (74) 34/47 (72) 0.99 (0.66, 1.50) Bone-Only 493 142/284 (50) 115/209 (55) 0.74 (0.58, 0.95) Liver/Lung Mets 1111 365/639 (57) 291/472 (62) 0.81 (0.70, 0.95) Age <40 193 40/106 (38) 44/87 (51) 0.78 (0.51, 1.21) Age >70 403 159/247 (64) 106/156 (68) 0.86 (0.67, 1.09) ECOG 1 851 305/499 (61) 239/352 (68) 0.78 (0.66, 0.93) White 1594 529/919 (58) 407/675 (60) 0.88 (0.77, 1.00) Asian 438 113/269 (42) 89/169 (53) 0.59 (0.45, 0.78) Black or African American 43 14/25 (56) 11/18 (61) 0.80 (0.36, 1.76) Additional clinicopathologic subgroup analyses conducted with results not shown.