Abstract PS5-32: Overall survival outcomes of combination anastrozole and fulvestrant in molecular subsets of hormone receptor-positive breast cancer

Background: The combination of anastrozole and fulvestrant (A+F) is associated with improvement in overall survival (OS) as compared to anastrozole (A) in patients (pts) with hormone receptor-positive (HR+) breast cancer (BC), specifically in pts with endocrine naive disease or in pts with long disease-free interval (Mehta et al. NEJM 2019). We performed an IRB-approved retrospective assessment of the time-to-treatment failure (TTF) and overall survival (OS) outcomes in pts treated at our institution with A+F, and assessed the impact of A+F in various molecularly defined subsets of pts. Methods: We reviewed charts of 118 pts with advanced HR+ BC who received A+F. Pts with brain metastases were not excluded. Performance status (PS) ranged from 0-3. We compared TTF and OS outcomes in pts with and without molecular aberrations including HER2 overexpression/amplification, or mutations in PIK3CA, ESR1 or BRCA1/2. HER2 status was tested through tumor. PIK3CA and ESR1 were tested on tumor or ctDNA by next generation sequencing. Germline/somatic BRCA1/2 status was assessed either through ctDNA or germline testing. Kaplan-Meir survival curves were constructed. Primary statistical analysis was log-rank test, followed by Cox regression to estimate the hazard ratio and 95% confidence intervals. All p values are 2-sided. Results: Overall 68 patients had endocrine-sensitive (ES) disease and 50 patients had acquired endocrine-resistant (ER) disease. Median TTF was 26 months in the ES group vs. 10 months in the ER group (HR: 0.47;95% Cl: 0.30 - 0.75, p= 0.001). Median OS was 57 months in the ES group vs. 38 months in the ER group (HR: 0.51; 95% Cl: 0.30 - 0.86, p= 0.01). Among the 31 pts tested for PIK3CA mutation, 21 pts were negative (control) and 10 pts were positive (PIK3CA mutant). Median TTF was 23 months for control vs.14 months for PIK3CA mutant (HR: 0.89; 95% CI: 0.40 -1.95, p = 0.76). Median OS was not reached for control vs. 44 months for PIK3CA mutant (HR: 0.50; 95% Cl: 0.16 - 1.56, p = 0.23). Among the 35 pts tested for ESR1 mutation, 27 pts were negative (control) and 8 patients were positive (ESR1 mutant). Median TTF was 26 months for control vs. 10 months for ESR1 mutant (HR: 0.59; 95% CI: 0.23 - 1.52, p = 0.20). Median OS was 66 months for control vs. 65 months for ESR1 mutant (HR: 1.63; 95% Cl: 0.44 - 5.95, p = 0.46). In the 17 pts tested for BRCA mutation (germline or somatic), 6 of them were positive (BRCA mutant) and 11 of them were negative (control). Median TTF was 36 months for control vs. 10 months for BRCA mutant (HR: 0.40; 95% CI: 0.12 - 1.40, p = 0.09). Median OS was 35 months for control but has not been reached in the BRCA mutant group (HR: 1.16; 95% Cl: 0.23 - 5.88, p = 0.93). Of 118 patients, 92 pts were HER2 negative (control) and 26 patients were HER2 positive. Median TTF was 23 months for control vs. 14 months for HER2+ group (HR: 0.80; 95% CI: 0.46 - 1.39, p = 0.42). Median OS was 52 months for control vs. 40 months for HER2+ group (HR: 0.87; 95% Cl: 0.47 - 1.64, p = 0.67). Conclusions: The time-to-treatment failure and overall survival in the endocrine-sensitive disease are 2-fold higher compared to the endocrine-resistant disease. Patients with PIK3CA, ESR1 or BRCA1/2 mutation or with HER2 overexpression/amplification historically have poor survival outcomes, but in hypothesis-generating analysis, we showed statistically similar overall survival outcomes in these patients treated with anastrozole plus fulvestrant, compared to controls without these poor prognostic features. We suggest that anastrozole plus fulvestrant should be the preferred partner with molecularly targeted agents. Citation Format: Tianyi Tang, Yu Cheng, Ritesh Parajuli, Neha Patel, Min-Ying Su, Chaitali Nangia, Rita S Mehta. Overall survival outcomes of combination anastrozole and fulvestrant in molecular subsets of hormone receptor-positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-32.