Abstract P4-13-08: Time to treatment discontinuation of second-line fulvestrant monotherapy for HR+/HER2− metastatic breast cancer in the real-world setting

Background: Current treatment guidelines recommend sequential hormone therapy for patients with hormone receptor–positive (HR+) metastatic breast cancer (mBC) who are not in visceral crisis or who are not refractory to endocrine treatment. Second-line (2L) fulvestrant monotherapy is one option for patients with HR+ mBC that is human epidermal growth factor receptor 2 negative (HER2–) who progress on first-line (1L) treatment that may have included palbociclib. Using real-world data, we evaluated the differences in time to treatment discontinuation (TTD) of 2L fulvestrant monotherapy between groups of patients with HR+/HER2− mBC who did and did not receive 1L palbociclib.

Methods: Using a Flatiron Health EHR-derived database, we examined TTD of 2L fulvestrant monotherapy among 188 patients who progressed on 1L endocrine therapy. Eligibility criteria included a confirmed diagnosis of HR+/HER2− mBC between 1 Jan 2015 and 31 Oct 2017 and treatment with single-agent fulvestrant in the 2L metastatic setting. 2L fulvestrant monotherapy treatment was considered discontinued if (1) third-line (3L) treatment was initiated, (2) death occurred within 60 days of the last administration of 2L fulvestrant monotherapy, or (3) the duration between last administration of 2L fulvestrant monotherapy and last visit date was ≥ 60 days. Patients who did not meet this definition were censored. TTD was defined as the time from the first to the last administration of 2L fulvestrant monotherapy, the day before the 3L start date, death date, or the end of study (30 Apr 2018), whichever came first.TTD was estimated by Kaplan-Meier methods and stratified by previous use of 1L palbociclib. Log-rank test was used to test for differences.

Results: Overall, the median TTD of 2L fulvestrant monotherapy was 114 days (95% CI: 102, 127). For patients who previously received 1L palbociclib, the median TTD of 2L fulvestrant monotherapy was 102 days (95% CI: 85, 119) compared with 127 days (95% CI: 112, 141) for those who did not receive 1L palbociclib (log-rank P = 0.006). Patients who received 2L fulvestrant monotherapy and who had been previously treated with 1L palbociclib (n = 88) were more likely to be White (72.7% vs. 68.0%), younger (mean: 65.0 vs. 72.1 years), treated in an academic institution (9.1% vs. 4.0%), and experience longer median duration of 1L treatment (290.5 days vs. 211.0 days) compared with patients receiving 2L fulvestrant monotherapy who did not previously receive 1L palbociclib (n = 100).

Conclusions: In general, half of patients on 2L fulvestrant monotherapy discontinued treatment in < 4 months. Patients who previously received 1L palbociclib had shorter TTD of 2L fulvestrant monotherapy. Our data identify a potential area of unmet medical need for patients with HR+/HER2− mBC who are treated with fulvestrant monotherapy in the 2L setting and who previously received 1L palbociclib. Further investigation is warranted to examine whether observed results are driven by endocrine resistance or by confounding, selection, or channeling effects of new drugs.

Citation Format: Luhn P, O'Hear C, Ton TG, Sanglier T, Hsieh A, Oliveri D, Chuo J, Xiao Y, Emens L. Time to treatment discontinuation of second-line fulvestrant monotherapy for HR+/HER2− metastatic breast cancer in the real-world setting [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 P4-13-08.