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Meta-Analysis
. 2021 Dec;6(6):100332.
doi: 10.1016/j.esmoop.2021.100332. Epub 2021 Dec 1.

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

E Munzone  1 , E Pagan  2 , V Bagnardi  2 , E Montagna  3 , G Cancello  3 , S Dellapasqua  3 , M Iorfida  3 , M Mazza  3 , M Colleoni  4
Affiliations
Meta-Analysis

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

E Munzone et al. ESMO Open. 2021 Dec.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: CDK4/6 inhibitors; ER-positive/HER2-negative; PFS2; TTC; endocrine therapy; metastatic breast cancer.

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Conflict of interest statement

Disclosure EMu has acted as a consultant to Pierre Fabre, Genomic Health and Eisai; EMo had consulting or advisory role from Pierre Fabre; MC has received a research grant from Roche. All other authors have declared no conflicts of interest.

Figures

Figure 1
Figure 1
Forest plot for second progression-free survival (PFS2) and time to chemotherapy (TTC). CI, confidence interval; HR, hazard ratio; NSAI, nonsteroidal aromatase inhibitor; TAM, tamoxifen.
See this image and copyright information in PMC

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