Outcomes with first-line (1L) ribociclib (RIB) + endocrine therapy (ET) vs physician’s choice combination chemotherapy (combo CT) by age in pre/perimenopausal patients (pts) with aggressive HR+/HER2− advanced breast cancer (ABC): A subgroup analysis of the RIGHT Choice trial.

1063 Background: The progression-free survival (PFS; primary endpoint) results from the Phase II RIGHT Choice trial demonstrated a statistically significant median PFS (mPFS) benefit of ≈1 y with RIB + ET over combo CT (mPFS, 24.0 vs 12.3 mo; hazard ratio [HR], 0.54; 95% CI, 0.36-0.79; P = .0007) in pts with aggressive HR+/HER2− ABC. Younger pts with aggressive ABC have a worse prognosis, which impacts treatment (tx) decisions. Hence, a subgroup analysis of key efficacy endpoints from RIGHT Choice by age (< 40 vs ≥ 40 y) was undertaken. Methods: Pre/perimenopausal pts (aged 18-59 y) with HR+/HER2− ABC and no prior systemic therapy for ABC were randomized 1:1 to either RIB with letrozole/anastrozole + goserelin or investigator’s choice of combo CT (docetaxel + capecitabine, paclitaxel + gemcitabine, or capecitabine + vinorelbine). Pts in the trial had ABC not amenable to curative therapy and for which combo CT was clinically indicated by physician’s judgment (ie, symptomatic visceral metastases, rapid progression of disease or impending visceral compromise, or markedly symptomatic non-visceral disease). Results: In total, 70 pts were aged < 40 y and 152 were aged ≥ 40 y. In the combo CT arm, pts aged < 40 y fared worse and had a shorter mPFS, shorter median time to tx failure (mTTF), and higher 3-month tx failure rate (TFR) than pts aged ≥ 40 y. Pts aged < 40 y showed a significant PFS benefit with RIB + ET vs combo CT (mPFS, not reached [NR] vs 10.2 mo; HR, 0.38). This PFS benefit with RIB + ET over combo CT was also observed in pts aged ≥ 40 y (21.2 vs 16.0 mo; HR, 0.71). Regardless of age, the mTTF was longer and the 3-month TFR was lower in the RIB + ET arm than the combo CT arm. The median time to response (mTTR), overall response rate (ORR), and clinical benefit rate (CBR) were similar between the two tx arms in both age groups. Conclusions: This analysis demonstrated a clinically meaningful PFS benefit and improved secondary outcomes with 1L RIB + ET over combo CT along with similar treatment responses in both tx arms in pts aged < 40 y as well as in those ≥ 40 y with aggressive HR+/HER2− ABC. This analysis supports RIB + ET as a preferred tx option in this pt population, including younger pts aged < 40 y. Clinical trial information: NCT03839823 . [Table: see text]