{Reference Type}: Meta-Analysis
{Title}: The role of CDK4/6 inhibitors in older and younger patients with breast cancer: A systematic review and meta-analysis.
{Author}: Petrelli F;Dottorini L;Di Menna G;Borgonovo K;Parati MC;Rea CG;Ghilardi M;Ghidini A;Luciani A;
{Journal}: Breast
{Volume}: 71
{Issue}: 0
{Year}: 2023 Oct 13
{Factor}: 4.254
{DOI}: 10.1016/j.breast.2023.05.002
{Abstract}: <B>BACKGROUND: </B>Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have an extremely important impact on the treatment of hormone-sensitive breast cancer (BC) and have radically changed the first-line treatment for metastatic disease with increased rates of treatment response, overall survival (OS), and progression-free survival (PFS). We performed a pooled analysis of randomized trials to validate or refute the hypothesis that there is a significant survival benefit of adding anti-CDK4/6 inhibitors to standard endocrine therapy (ET) in older patients with advanced BC.<BR><B>METHODS: </B>We selected only English-language phase II/III randomized controlled trials that compared ET alone with ET with anti-CDK4/6 inhibitors in the treatment of advanced BC, with subgroups reporting the outcomes of elderly patients (usually at least 65 years). The primary endpoint was OS.<BR><B>RESULTS: </B>The review process led to the inclusion of 12 articles and two meeting abstracts, including a total of 10 trials. The addition of CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced mortality risk by 20% in younger patients (fixed-effect model; HR 0.80; 95% CI 0.72-0.9; p < 0.01) and 21% in older BC patients (HR 0.79; 95% CI 0.69-0.91; p < 0.01). No OS data were available for patients ≥70 years.<BR><B>CONCLUSIONS: </B>This large, pooled analysis is the first to demonstrate that CDK4/6 inhibitors confer OS and PFS benefits in elderly patients (those aged ≥65 years) with advanced ER + BC and to indicate that it should be discussed with and offered to all patients after geriatric assessment and according to the toxicity profile.