Certain breast cancer subtypes may benefit more from ribociclib/ribociclib combination than chemotherapy

According to a subgroup analysis of the phase 2 RIGHT Choice study (NCT03839823) published in 2024, compared with combination chemotherapy, patients with breast cancer luminal-B/HER2E intrinsic subtype who received ribociclib and endocrine therapy showed a trend of benefit in progression-free survival (PFS). In patients with lower baseline expression levels of immune-related genes, the benefit of ribociclib combined with endocrine therapy on PFS also showed a more obvious trend. The opposite results in the [chemotherapy] group suggest that these characteristics merit further investigation for their potential predictive value. These data are hypothesis generated and should be interpreted with caution due to the small sample size.

In this analysis, there were 27 samples available from the rebociclib group, of which 22.2% were luminal-A, 51.9% were luminal-B, 22.2% were HER2E, and 3.7% were basal-like. Among the 22 available samples in the chemotherapy group, 50.0% were luminal-A, 40.9% were luminal-B, and 9.1% were HER2E.

In patients with luminal-A breast cancer, the median PFS in the rebociclib group was 32.5 months (HR=0.88; 95% CI, 0.20-3.91) compared with not reaching (NR) in the chemotherapy group. For other subtypes, in luminal-B breast cancer, the median PFS was 38.0 months in the ribociclib group and 21.7 months in the chemotherapy group (HR=0. 64; 95% CI, 0.18-2.20), and in the HER2E subtype, the median PFS was 17.4 months and 8.0 months (HR=0.23; 95% CI, 0.03-1.66).

The researchers also evaluated median PFS in a group of patients with the luminal-B and HER2E subtypes of breast cancer, both of which are associated with poor prognosis. In this group, median PFS was 38.0 for patients who received ribociclib plus endocrine therapy, compared with 18.4 months for those who received combination chemotherapy (HR=0.58; 95% CI, 0.21-1.62). In the group of patients treated with ribociclib, patients with high ESR1 expression had a longer median PFS compared with patients with low ESR1 expression (38.0 months vs 32.5 months; HR=1.59; 95% CI, 0.20-12.44).

The analysis also included tumor inflammation or immune-related genes in the ribociclibgroup/Patients with low expression of cells, including tumor inflammatory signatures and T cell expression. These patients had longer median PFS compared with patients whose tumors had high expression of inflammatory signatures (NR vs 11.4 months; HR=0.17; 95% CI, 0.04-0.76) and T cell expression (NR vs 10.3 months). In the chemotherapy group, patients with low expression of immune-related genes/cells had shorter median PFS than patients with high expression of tumor inflammatory signatures (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).

There were comparable and consistent trends in PFS benefit for most other immune-related genes/cell expression and signatures of low versus high expression levels. Additionally, lower gene expression in patients in the ribociclib group was associated with a higher PFS benefit, and higher gene expression in the chemotherapy group was associated with a higher PFS benefit.

In the Phase 2 RIGHT Choice study, researchers enrolled pre- and postmenopausal patients who had not received prior systemic therapy for aggressive HR-positive, HER2-negative advanced breast cancer. Patients were randomized in a 1:1 ratio to receive reboxiclib plus letrozole (Femara)/anastrozole (Arimidex) and goserelin or physician's choice of combination chemotherapy.

This subgroup analysis includedBaseline tumor samples from 49 patients that were microdissected and analyzed for gene expression using NanoString nCount BC360 and PanCancer IO 360 panels. The researchers defined high and low baseline gene/trait expression levels as greater than and less than or equal to the median level, respectively.

Previous findings from the RIGHT Choice study, published in May 2024, showed that the median PFS benefit of first-line reboxil plus endocrine therapy was statistically significant compared with combination chemotherapy in patients with clinically aggressive HR-positive, HER2-negative advanced breast cancer (HR=0.61; 95% CI, 0.43-0.87; P=0.003).

Reference materials:https://www.onclive.com/view/certain-breast-cancer-subtypes-may-derive-a-greater-benefit-with-ribociclib-combo-vs-chemo