Abstract P5-21-18: Subsequent treatment for postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer who received ribociclib + letrozole vs placebo + letrozole in the phase III MONALEESA-2 study

Background: In the Phase III MONALEESA-2 study (NCT01958021), ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor [CDK4/6i]) + letrozole (LET) significantly prolonged progression-free survival (PFS) vs placebo (PBO) + LET in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC). The optimal treatment sequence following first-line CDK4/6i-based therapy is not yet known. Here we report the subsequent therapies received following discontinuation from MONALEESA-2. Methods: The MONALEESA-2 study enrolled 668 patients (pts) with HR+, HER2– ABC. Pts were randomized 1:1 to receive RIB (600 mg/day; 3-weeks-on/1-week-off) + LET (2.5 mg/day; continuous) or PBO + LET. Following discontinuation of MONALEESA-2 study treatment, pts were followed for information regarding post-study treatment, including type and duration of therapy. Results: At data cut-off (January 2, 2017), the median duration of follow-up was 26.4 months. Median PFS was 25.3 vs 16.0 months in the RIB + LET vs PBO + LET arms (hazard ratio=0.568; 95% confidence interval [CI]: 0.457–0.704; p=9.63x10–8). 203 (60.8%) vs 246 (73.7%) pts had discontinued RIB + LET vs PBO + LET. The median time to end of treatment was 20.3 months in the RIB + LET arm vs 13.7 months in the PBO + LET arm. First subsequent antineoplastic treatment was reported for 172/203 (84.7%) vs 212/246 (86.2%) pts who received RIB + LET vs PBO + LET; second subsequent therapy was reported for 45/203 (22.2%) vs 68/246 (27.6%) pts. The median time to first subsequent therapy (from randomization to the first post-study dose of therapy) was 24.2 (95% CI: 20.9–27.6) vs 16.7 (95% CI: 14.8–19.3) months in pts who received RIB + LET vs PBO + LET; median time to initiation of second subsequent therapy was not reached in either arm. The most common type of first subsequent therapy was single-agent hormonal therapy in 90 (44.3%) vs 87 (35.4%) pts who discontinued RIB + LET vs PBO + LET; chemotherapy was the most common second subsequent therapy in 20 (9.9%) vs 36 (14.6%) pts. Chemotherapy alone was the first subsequent treatment after MONALEESA-2 discontinuation in 32 (15.8%) vs 55 (22.4%) pts treated with RIB + LET vs PBO + LET. Conclusions: RIB + LET significantly prolongs PFS and delays the start of subsequent lines of therapy vs PBO + LET in pts with HR+, HER2– ABC. The most common first subsequent therapy following discontinuation of RIB + LET or PBO + LET was single-agent hormonal therapy, and fewer pts treated with RIB + LET received subsequent chemotherapy compared with those who received PBO + LET. Citation Format: Blackwell KL, Paluch-Shimon S, Campone M, Conte P, Petrakova K, Favret A, Blau S, Beck JT, Miller M, Sutradhar S, Monaco M, Burris HA. Subsequent treatment for postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer who received ribociclib + letrozole vs placebo + letrozole in the phase III MONALEESA-2 study [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 P5-21-18.