Efficacy and tolerability of CDK 4/6 inhibitors in HR-positive HER2-negative de novo metastatic breast cancer patients aged ≥ 70 years

BACKGROUND: Current guidelines recommend endocrine therapy with CDK 4/6 inhibitors as the first and most strongly evidenced treatment for patients with hormone receptor-positive, HER2-negative metastatic breast cancer, unless they are experiencing visceral crisis or resistance to endocrine therapy. CDK 4/6 inhibitors can cause hematological and gastrointestinal toxicity. In case of toxicity, drug doses need to be reduced. Sometimes, depending on the degree of toxicity, taking a break or even stopping treatment may be considered. METHODS: All patients included in our study were 70 years of age or older, had de novo metastatic disease, were hormone receptor-positive and HER2-negative, and were receiving CDK 4/6 inhibitors as part of their metastatic first-line treatment. Recorded common side effects of CDK 4/6 inhibitors. Survival analyses were conducted on patients who had dose reductions due to these side effects. Additionally, OS and PFS were compared according to the type of CDK 4/6 inhibitor the patients received and the Charlson comorbidity index. Our study was conducted retrospectively and as a single-center study. RESULTS: Median OS was 33.0 months (27.0-38.9). Median OS was statistically significantly better in patients with a Charlson comorbidity index < 10 (patients aged 70-79 years with no comorbidities other than metastatic breast cancer) compared to those with a Charlson comorbidity index ≥ 10 (patients aged 80 and over or with comorbidities other than metastatic breast cancer) (41.5 vs. 15.0 months, p < 0.001). CDK 4/6 inhibitor selection and dose reduction did not significantly affect median OS. Median PFS was 27.0 months (22.5-31.4). Similar to variables affecting OS, PFS was significantly worse in patients with a Charlson comorbidity index ≥ 10 and in patients with more than 3 bone metastases. CONCLUSIONS: A review of the literature reveals that studies on the efficacy and tolerability of CDK 4/6 inhibitors have primarily focused on a limited number of patients aged 70 years or older. The results of these studies, similar to our study, generally indicate that efficacy and survival are similar to those in younger patients, and that dose reductions do not significantly impact survival. Furthermore, there are no studies in the literature yet that examine the relationship between the Charlson comorbidity index and survival in elderly patients with multiple comorbidities who are receiving CDK 4/6 inhibitors.