Abstract P4-13-06: Real-world experience using exemestane and everolimus in patients with hormone receptor positive/HER2 negative breast cancer with and without prior CDK4/6 inhibitor exposure

Abstract

Background: For patients with metastatic hormone receptor (HR)-positive, HER2-negative breast cancer who progress on a non-steroidal aromatase inhibitor (NSAI), exemestane plus everolimus (EE) has been shown to prolong progression-free survival in comparison to exemestane alone. In the current era, many patients are now receiving a CDK4/6 inhibitor with first-line NSAI therapy. There is limited data describing the utilization and effectiveness of treatments following hormonal therapy - CDK4/6 inhibitor combinations, including EE. The aim of this study was to describe the real-world clinical experience and outcomes associated with EE amongst patients with and without prior CDK4/6 inhibitor exposure treated in our provincial jurisdiction. Methods: All patients prescribed EE from January 1, 2016 through May 10, 2018 were obtained from the Alberta Health Services CancerControl Breast Data Mart (BDM). Patients with HER2+ disease, had received <1 cycle of EE or who had been on a placebo controlled trial of hormonal therapy +/- CDK4/6 inhibitor prior to EE were excluded. Review of the electronic medical record was undertaken to obtain detailed information on lines of treatment prior to EE, EE dosing and reason for EE discontinuation. The cohort was described and analyzed in total and by prior CDK4/6 inhibitor exposure. Time on treatment (TOT) was defined as start of EE to last dose or June 11, 2018 (censoring for data extraction) and was calculated using the Kaplan Meier method. The log rank test was used to compare TOT. Results: There were 110 patients extracted and 88 eligible for analysis (3 excluded for HER2+ disease, 14 for receipt of <1 cycle EE and 5 for participation on a placebo controlled trial of hormonal therapy +/- CDK4/6 inhibitor prior to EE. Median age 62.4 years (range 32.1-86.6 years). EE was administered first line in 12.5%, second line in 46.6% and third or greater line in 40.9%. Median time from start of first line therapy to start of EE was 19.3 months (range 0.3-72.1 months). Visceral metastases at start of EE in 62.5%. EE mean starting dose 7.3 mg (SD 2.5 mg) and mean last dose recorded 7.0 mg (SD 2.7 mg). At time of data extraction, 69 patients had stopped EE, 68.1% for progression and 31.9% for toxicity or other reason. Twenty patients had hormonal therapy + CDK4/6 inhibitor prior to EE. In the first line setting, 10 patients had letrozole and palbociclib. In the second line setting or greater, 5 patients had letrozole + palbociclib, 1 patient had tamoxifen + palbociclib and 4 patients had fulvestrant + palbociclib. Median time on hormonal therapy + CDK4/6 inhibitor was 12.0 months (range 4.0-20.9 months). Those with hormonal therapy + CDK4/6 inhibitor were more likely to have visceral metastases (p=0.02). Median time on treatment for the CDK4/6 exposed vs naïve groups was similar (5.8 vs 5.3 months, p=0.952). Median overall survival not yet reached. Conclusion: In a cohort of patients who have progressed on hormonal therapy + CDK4/6 inhibitor within 2 years, subsequent EE is a clinically meaningful treatment option in the setting of HR-positive/HER2-negative metastatic breast cancer. TOT was similar for CDK4/6 inhibitor exposed and naïve patients. Citation Format: Lupichuk SM, Recaldin B, Nixon NA, Mututino A, Joy AA. Real-world experience using exemestane and everolimus in patients with hormone receptor positive/HER2 negative breast cancer with and without prior CDK4/6 inhibitor exposure [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-13-06.

Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial

“…Fifth, no FAKTION participants had received previous CDK4/6 inhibitor therapy, which is now standard of care in combination with an aromatase inhibitor or fulvestrant. However, clinical [30][31][32] and preclinical data 33,34 suggest that previous exposure to CDK4/6 inhibition should not abrogate the incremental benefit seen with capivasertib. Preclinical data suggest that AKT inhibition might be superior to PI3K inhibition in this setting, 29 but formal confirmation of this theory in a randomised trial is required.…”

Therapy options after CDK4/6 inhibitors for HR+, HER2- postmenopausal metastatic/recurrent breast cancer in Japan: a role for mammalian target of rapamycin inhibitors?

“…These data indicate that the tolerability and efficacy of everolimus plus exemestane combination therapy are not affected by history of CDK4/6 inhibitor use. Likewise, in a real-world clinical study comparing duration of everolimus/exemestane combination therapy with history of CDK4/6 inhibitor use in patients with HR+, HER2-MBC, no significant difference in treatment duration was observed (5.8 months in patients with and 5.3 months in patients without a history of CDK4/6 inhibitor use; p = 0.95), indicating that prior use of CDK4/6 inhibitors did not impact subsequent treatment durations with everolimus/exemestane [47]. In a retrospective study conducted at a single center in the US, the efficacy of palbociclib and subsequent therapy for HR+, HER2-MBC was investigated [48].…”

Novel Treatment Strategies for Hormone Receptor (HR)-Positive, HER2-Negative Metastatic Breast Cancer

“…However, no patients from the BOLERO-2 trial had previously been treated with CDK4/6is. Nonetheless, the administration of ET in combination with everolimus after disease progression during CDK4/6i treatment is substantiated by a large number of studies [ 75 , 76 , 77 , 78 ].…”