First-Line Ribociclib Plus Endocrine Therapy Significantly Improved PFS Among Pre-Menopausal Patients With HR-Positive, HER2-Negative Advanced Breast Cancer

Final Analysis Results from the Phase 2 RIGHT Choice Trial

Results from the phase 2 RIGHT Choice trial demonstrated that first-line ribociclib plus endocrine therapy significantly improved progression-free survival (PFS) with similar response rates and better tolerability compared to chemotherapy among pre-menopausal patients with clinically aggressive hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. 

According to Yen-Shen Lu, MD, PhD, National Taiwan University Hospital, Taipei, Taiwan, and coauthors, “an unmet medical need exists in the HR+/HER2– [advanced breast cancer] patient population for therapy options that provide a rapid response and durable efficacy while sparing patients the toxicities associated with combination [chemotherapy].”

In this multicenter, open-label trial, 222 pre/perimenopausal patients were randomized on a 1-to-1 basis to receive either ribociclib (600 mg once daily for 3 weeks on and 1 week off) plus letrozole/anastrozole and goserelin (n = 112) or investigators’ choice combination chemotherapy (n = 110). The primary end point was PFS. Secondary end points included overall response rate (ORR), time to response, and safety. 

At a median follow-up of 37 months, treatment was completed by 31.3% of patients in the ribociclib arm and 15.5% of patients in the chemotherapy arm. Median PFS was 21.8 months in the ribociclib arm and 12.8 months in the chemotherapy arm (hazard ratio [HR] 0.61; 95% confidence interval [CI], 0.43 to 0.87; P = .003). ORR was 66.1% in the ribociclib arm and 61.8% in the chemotherapy arm and median time to response was 4.9 months and 3.2 months, respectively. 

Grade 3/4 adverse events were experienced by 79.5% of patients in the ribociclib arm and 73% of patients in the chemotherapy arm. The most common events included neutropenia and leukopenia. Serious treatment-related adverse events were reported in 2 patients in the ribociclib arm and 8 patients in the chemotherapy arm. Treatment discontinuation due to an adverse event occurred in 6.3% of patients in the ribociclib arm and 27% of patients in the chemotherapy arm. 

“This final analysis of the RIGHT Choice trial showed a clinically meaningful, statistically significant PFS benefit with first-line ribociclib plus [endocrine therapy] over combination [chemotherapy] in premenopausal women with clinically aggressive HR+/HER2– [advanced breast cancer] in which combination [chemotherapy] is typically is used to achieve a rapid tumor response,” concluded Dr Lu and coauthors. “Ribociclib plus [endocrine therapy] could be considered a first-line treatment option in this patient population.”

As Journal of Clinical Oncology Senior Deputy Editor Kathy Miller, MD, Indiana University, Bloomington, Indiana, added “the ‘conventional wisdom’ that patients with visceral disease need [chemotherapy] even if estrogen receptor-positive should be retired.” 

Source: 

Lu YS, Mahidin EIBM, Azim H, et al. Final results of RIGHT choice: Ribociclib plus endocrine therapy versus combination chemotherapy in premenopausal women with clinically aggressive hormone receptor-positive/human epidermal growth factor receptor 2–negative advanced breast cancer. J Clin Oncol. Published online: May 21, 2024. doi: 10.1200/JCO.24.00144