Systematic review and meta-analysis of post-progression outcomes in ER+/HER2− metastatic breast cancer after CDK4/6 inhibitors within randomized clinical trials

• Published in: ESMO open 2021-12, Vol.6 (6), p.100332-100332, Article 100332
• Main Authors: Munzone, E., Pagan, E., Bagnardi, V., Montagna, E., Cancello, G., Dellapasqua, S., Iorfida, M., Mazza, M., Colleoni, M.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Hormonal - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; CDK4/6 inhibitors; Cyclin-Dependent Kinase 4 - antagonists & inhibitors; Cyclin-Dependent Kinase 6 - antagonists & inhibitors; endocrine therapy; ER-positive/HER2-negative; Female; Humans; metastatic breast cancer; PFS2; Protein Kinase Inhibitors - therapeutic use; Quality of Life; Randomized Controlled Trials as Topic; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Review; TTC
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2021.100332

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and endocrine therapy (ET) deeply transformed the treatment landscape of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer. Randomized clinical trials suggest that second progression-free survival (PFS2) was not compromised and time to subsequent chemotherapy (TTC) may be delayed. We carried out a meta-analysis to assess the benefit on PFS2 and on delaying the TTC. We conducted a systematic literature search of randomized clinical trials with CDK4/6 inhibitors and ET reporting PFS2 or TTC of HR+/HER2− pre- or postmenopausal metastatic breast cancer. We also reviewed abstracts and presentations from all major conference proceedings. We calculated the pooled hazard ratios (HR) for PFS2 and TTC using random-effects models with 95% confidence intervals (CI). I2 was used to quantify heterogeneity between results of the studies. Eight studies (MONALEESA-2/3/7, MONARCH-2/3, PALOMA-1/2/3) were included in this analysis (N = 4580 patients). PFS2 benefit was observed in patients who received CDK4/6 inhibitors plus ET (pooled HR = 0.68, 95% CI = 0.62-0.74, I2 = 0%) and also a delay in subsequent TTC (pooled HR = 0.65, 95% CI = 0.60-0.71, I2 = 0%). A benefit in terms of PFS (pooled HR = 0.55, 95% CI = 0.51-0.59, I2 = 0%) and overall survival (pooled HR = 0.76, 95% CI = 0.69-0.84, I2 = 0%) was also observed. CDK4/6 inhibitors plus ET compared with ET alone improve PFS2 and TTC. The delay of chemotherapy may postpone the start of a more toxic treatment option, delaying related toxicities and potentially maintaining a better quality of life for patients, for a longer time. The benefit in PFS2 may postpone the onset of endocrine resistance and help further validate this treatment approach. •Eight RCTs (MONALEESA-2/3/7, MONARCH-2/3, PALOMA-1/2/3) were included in this analysis on pooled HR for PFS2 and TTC.•Patients who received CDK4/6 inhibitors plus ET had a clear PFS2 benefit and a delay in subsequent TTC.•CDK4/6 inhibitors plus ET compared with ET alone improve PFS2 and TTC.