Final results of RIGHT Choice, ribociclib plus endocrine therapy versus combination chemotherapy in premenopausal women with clinically aggressive HR+/HER2- advanced breast cancer

Key message:

The RIGHT Choice study was a randomized phase II trial of 222 treatment-naïve premenopausal women with aggressive HR+/HER2- advanced breast cancer. Participants received ribociclib plus endocrine therapy (ET) and goserelin or investigator-selected combination chemotherapy (CT), which included options such as docetaxel + capecitabine, paclitaxel + gemcitabine, and capecitabine + vinorelbine. Patients were classified as having aggressive disease based on rapid progression or symptomatic disease, with 47.7% identified by the investigator as having visceral crisis. Median progression-free survival (PFS) was 21.8 months in the ribociclib plus ET group compared with 12.8 months in the CT group. In addition, the combination of ribociclib with ET was associated with fewer symptomatic adverse events. Subgroup analysis showed that ribociclib in combination with ET provided similar benefits compared with CT in patients with visceral crisis.

These results support the use of ribociclib in combination with endocrine therapy and goserelin as first-line treatment for all premenopausal patients with aggressive HR+/HER2- advanced breast cancer.

SUMMARY

Target:

A direct comparison of the efficacy of a cyclin-dependent kinase 4/6 inhibitor in combination with endocrine therapy (ET) and combination chemotherapy (CT) has never been performed in patients with hormone receptor-positive advanced breast cancer (ABC) and negative for clinically aggressive cancer. . human epidermal growth factor receptor 2 (HR+/HER2-).

Patients and methods:

In this open-label, multicenter, randomized, phase 2 trial, pre-/perimenopausal women with clinically aggressive HR+/HER2- ABC were randomized 1:1 to first-line ribociclib (600 mg daily; 3 weeks on, 1 week plus). letrozole/anastrozole and goserelin or investigator-selected CT combination (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary endpoint was progression-free survival (PFS).

Results:

Among 222 patients randomized to ribociclib plus ET (n=112) or combined CT (n=110), 150 (67.6%) had symptomatic visceral metastases, and 41 (18.5%) had rapid disease progression according to investigator’s assessment, and 31 (18.5%) experienced rapid progression of the disease. 14.0%) had symptomatic non-visceral disease. Overall, 106 (47.7%) patients had visceral crisis as assessed by the investigator. The mean follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib group) and 15.5% (CT group) of patients completed study treatment and entered post-trial access. Median PFS was 21.8 months (ribociclib plus ET; 95% CI, 17.4–26.7 months) and 12.8 months (combined CT; 95% CI, 10.1–18.4 months); hazard ratio (HR) – 0.61; 95% CI, 0.43-0.87; P=0.003. The overall response rate and median response time in the ribociclib and CT groups were 66.1% and 61.8%, and 4.9 months and 3.2 months, respectively (HR 0.76; 95% CI 0.55-1.06) . A lower incidence of symptomatic adverse events was observed in the ribociclib group compared with the CT group.

Conclusions:

First-line ribociclib in combination with ET demonstrated significant PFS benefit, similar response rates, and better tolerability compared with combination chemotherapy in patients with clinically aggressive HR+/HER2- ABC.

References:

Yen-Shen Lu, Eznal Izwadi bin Mohd Mahidin et al.

DOI: https://doi.org/10.1200/JCO.24.00144.

Link: https://ascopubs.org/doi/10.1200/JCO.24.00144.

Fountain: BioPress