Ribociclib Plus Endocrine Therapy Shows Promise in Specific Breast Cancer Subtypes
核心洞察
A subgroup analysis of the RIGHT Choice study suggests ribociclib plus endocrine therapy may offer a progression-free survival (PFS) benefit in luminal B/HER2E breast cancer (搜索) subtypes.
Patients with low baseline expression of immune-related genes experienced a longer median PFS when treated with ribociclib and endocrine therapy compared to chemotherapy.
In luminal B/HER2E subtypes, ribociclib plus endocrine therapy showed a median PFS of 38.0 months versus 18.4 months with combination chemotherapy.
A subgroup analysis of the phase 2 RIGHT Choice study, presented at the 2024 San Antonio Breast Cancer (搜索) Symposium, indicates that ribociclib (Kisqali) in combination with endocrine therapy may provide a progression-free survival (PFS) advantage for patients with luminal B/HER2E intrinsic subtypes of breast cancer compared to combination chemotherapy.
The analysis, led by researchers including Yi-Sheng Lu and Chia-Ling Hsu, explored the efficacy of ribociclib plus endocrine therapy versus combination chemotherapy in pre- and post-menopausal patients with aggressive HR-positive, HER2 (搜索)-negative advanced breast cancer (搜索) who had not received prior systemic therapy. The study randomized patients 1:1 to either ribociclib plus letrozole/anastrozole and goserelin or physician’s choice of combination chemotherapy.
Progression-Free Survival Benefit
The subgroup analysis included baseline tumor samples from 49 patients, which underwent gene expression analysis. In patients with luminal A breast cancer (搜索), the median PFS in the ribociclib arm was 32.5 months compared to not reached (NR) in the chemotherapy arm (HR = 0.88; 95% CI, 0.20-3.91). For luminal B breast cancer, median PFS in the ribociclib and chemotherapy groups were 38.0 months vs 21.7 months (HR = 0.64; 95% CI, 0.18-2.20), and for the HER2E subtype, 17.4 months vs 8.0 months (HR = 0.23; 95% CI, 0.03-1.66).
When assessing median PFS in patients with luminal B and HER2E subtypes combined, those treated with ribociclib plus endocrine therapy had a median PFS of 38.0 months compared to 18.4 months in patients treated with combination chemotherapy (HR = 0.58; 95% CI, 0.21-1.62).
Impact of Gene Expression
The analysis also revealed that patients in the ribociclib group with high ESR1 expression had a longer median PFS compared to those with low ESR1 expression (38.0 months vs 32.5 months; HR = 1.59; 95% CI, 0.20-12.44). Furthermore, patients with low expression of tumor inflammation or immune-related genes/cells, including tumor inflammatory signature and T-cell expression, experienced a longer median PFS compared to those with high expression. Specifically, median PFS was not reached (NR) vs 11.4 months (HR = 0.17; 95% CI, 0.04-0.76) for tumor inflammatory signature and NR vs 10.3 months (HR = 0.2; 95% CI, 0.05-0.76) for T-cell expression.
In contrast, within the chemotherapy arm, patients with low expression of immune-related genes/cells had a shorter median PFS compared to those with high expression of tumor inflammatory signature (15.0 months vs NR; HR = 2.08; 95% CI, 0.62-6.93) and T-cell expression (12.8 months vs 18.4 months; HR = 1.8; 95% CI, 0.57-5.71).
Study Design and Previous Findings
The RIGHT Choice study enrolled patients with no prior systemic therapy for aggressive HR-positive, HER2 (搜索)-negative advanced breast cancer (搜索). Previous findings from the study, published in May 2024, demonstrated a statistically significant median PFS benefit from first-line ribociclib plus endocrine therapy compared with combination chemotherapy (HR = 0.61; 95% CI, 0.43-0.87; P = .003) in the overall patient population.
Researchers defined high and low baseline gene/signature expression levels as greater and less than or equal to the median level, respectively. The authors noted that these data are hypothesis-generating and should be interpreted with caution due to small sample sizes.