Abstract GS5-06: A U.S. food and drug administration pooled analysis of outcomes of older women with hormone-receptor positive metastatic breast cancer treated with a CDK4/6 inhibitor as initial endocrine based therapy
Authors: Singh H , Howie LJ , Bloomquist E , Wedam S , Amiri-Kordestani L , Tang S , Sridhara R , Ibrahim A , Goldberg K , McKee A , Beaver JA , Pazdur R 
Published: February 2018

Background: With recent FDA approvals of inhibitors of Cyclin Dependent Kinases 4 and 6 (CDK 4/6) in combination with endocrine therapy for the treatment of postmenopausal women with hormone-receptor positive metastatic breast cancer (MBC), an increasing number of older adults will be treated with this class of agents. An improved understanding of the safety and efficacy of CDK 4/6 inhibitors in this population is important to inform clinical decision making for the treatment of older patients.

Methods: Data from two prospective randomized controlled studies (n=1334) of different CDK 4/6 inhibitors in combination with an aromatase inhibitor for the initial treatment of postmenopausal patients with hormone-receptor positive MBC were pooled and analyzed. The effect of age on progression free survival (PFS) was explored using Kaplan Meier (KM) estimates and a Cox-proportional hazard model. Safety analysis included adverse events up to 30 days after last administration of drug based on standardized adverse event datasets.

Results: Age was balanced between the two studies, and between treatment arms within each study. The median age of women was 62 (range 23-91). Of the 1334 total patients, 42% were ≥65, and 24% were ≥ 70. For patients ≥70 who were treated with a CDK4/6 inhibitor in combination with an aromatase inhibitor, the estimated PFS was not reached (95% CI: 25.1months, NR) vs an estimated 18 months (95% CI: 13.8, 31.3) for those treated only with an aromatase inhibitor. For patients &lt;70 treated with a CDK4/6 inhibitor, the estimated PFS was 23.5 months (95% CI: 21.4, 25.7) vs an estimated 13.8 months (95% CI: 12.9, 16.5) for those treated only with an aromatase inhibitor.

Safety was evaluated in the 778 patients who received at least one dose of CDK4/6 inhibitor.

Adverse Events by Age in Patients Treated with a CDK4/6 Inhibitor Patients &lt; 65 yearsPatients≥65 yearsPatients≥70 years N=447N=331N=187 n (%)n (%)n (%)Grade 1-2 Adverse Events437 (98)324 (98)185 (99)Grade 3-4 Adverse Events340 (76)276 (83)159 (85)Serious Adverse Events72 (16)88 (27)50 (27)Adverse Events Leading to Discontinuation35 (8)56 (17)38 (20)Adverse Events leading to dose reduction and/or interruption323 (72)253 (76)147 (79)Selected Adverse Events  Neutropenia (all grades)341 (76)256 (77)150 (80)Grade 3-4 neutropenia292 (65)228 (69)134 (72)Infections (all grades)190 (43)165 (50)100 (53)Hepatotoxicty (all grades)79 (18)51 (15)34 (18)Grade 3-4 hepatotoxicity32 (7)16 (5)12 (6)Fatigue (all grades)195 (44)153 (46)89 (48)Grade 3 fatigue11 (2)11 (3)7 (4)

Conclusions: This exploratory analysis suggests the use of a CDK4/6 inhibitor in combination with an aromatase inhibitor for the first line treatment of HR+ MBC in older women results in similar efficacy benefit as seen in younger women. Although incidence and severity of Grade 1-4 adverse reactions appeared similar between age groups, greater serious adverse events and discontinuations occurred in patients ≥65. The inclusion of greater numbers of patients ≥70, in clinical trials will further inform clinicians about the safety and efficacy of CDK4/6 inhibitors in older adults.

Citation Format: Singh H, Howie LJ, Bloomquist E, Wedam S, Amiri-Kordestani L, Tang S, Sridhara R, Ibrahim A, Goldberg K, McKee A, Beaver JA, Pazdur R. A U.S. food and drug administration pooled analysis of outcomes of older women with hormone-receptor positive metastatic breast cancer treated with a CDK4/6 inhibitor as initial endocrine based therapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS5-06.