The combination of ribociclib and standard endocrine therapy improves invasive disease-free survival rates more than endocrine therapy alone in patients with early stage, hormone receptor–positive, HER2-negative (HR+/HER2-) breast cancer, according to recent data presented at ASCO 2023.
The standard treatment for HR+/HER2- advanced or metastatic breast cancer involves the use of endocrine therapies such as aromatase inhibitors, selective oestrogen receptor (ER) modulators, and selective ER down-regulators. However, a problem with this approach is the development of treatment resistance, which therefore requires additional therapeutic strategies.
Ribociclib is a cyclin-dependent kinase 4/6 inhibitor, approved in combination with endocrine therapy for treatment of HR+/HER2- advanced or metastatic breast cancer in both pre- and post-menopausal women.
In a 2019 study, use of ribociclib and endocrine therapy significantly improved progression-free survival and had manageable toxicity in both pre- or peri-menopausal and postmenopausal women with HR+/HER2- metastatic or advanced breast cancer. However, whether this combination would benefit women with early stage breast cancer remains unclear.
The current NATALEE trial – a phase III multi-centre, randomised, open-label trial – is designed to evaluate the efficacy and safety of ribociclib with endocrine therapy as adjuvant treatment in patients with HR+/HER2- early breast cancer.
Ribociclib and invasive disease-free survival
In an abstract presented at the American Society of Clinical Oncology 2023, women with early stage breast cancer given ribociclib were found to have a statistically significant and clinically meaningful improvement in invasive disease-free survival (iDFS) compared to standard endocrine therapy alone.
For the trial, both pre- and post-menopausal women were randomised 1:1 to ribociclib (RIB) and endocrine therapy (ET) or ET alone for up to three years. RIB was given at a dose of 40 mg daily (three weeks on and one week off) and ET comprised letrozole 2.5 mg daily or anastrozole 1 mg day for longer than five years.
In total, 5,101 participants were randomised to either RIB and ET (2,549) or ET alone and followed for a median of 34 months. The combination of RIB and ET showed a significantly longer iDFS than ET alone (Hazard ratio, HR = 0.75, 95% CI 0.62 – 0.91, p = 0.014). In addition, the three-year iDFS rates were rates were 90.4% vs 87.1% respectively.
The abstract also reported how this iDFS benefit was generally consistent across stratification factors and other subgroups. Moreover, while not reported, the authors indicated that the secondary endpoints of overall survival, recurrence-free survival and distant disease–free survival consistently favoured RIB. In addition, at the dosage used (400 mg), RIB had a favourable safety profile with no new signals.