Six RCTs were eligible including 3421 breast cancer patients....Our meta-analysis suggested that compared with endocrine therapy alone, the addition of CDK4/6 inhibitors significantly improved OS in patients with hormone receptor-positive, HER2-negative metastatic breast cancer.

This meta-analysis indicated that, compared with ET alone, treatment with CDK4/6 inhibitors plus ET was associated with significantly improved OS, PFS, and objective response rate among patients with HR-positive, ERBB2-negative metastatic breast cancer.

This study aimed to further assess the long-term efficacy and safety of CDK4/6i in HR+, Her2- ABC patients and find the suitable subject population for CDK4/6i by subgroup analysis….The pooled HR for OS was 0.76 (95% CI: 0.67–0.84), and the pooled HR for PFS was 0.55 (95% CI:0.50–0.59)....CDK4/6i meaningfully improved ORR both in intention-to-treat population (RR=1.47; 95% CI:1.29–1.67) and patients with measurable disease (RR=1.47; 95% CI:1.30–1.67),...

We investigated the association between baseline peripheral blood cells, or their early modifications (i.e. 2 weeks after treatment initiation), and the progression-free survival (PFS) of HR+/HER2− aBC patients treated with ETs plus CDK4/6i....Patients with high baseline lymphocytes and undergoing a lower reduction, or even an increase, of lymphocyte counts during CDK4/6i therapy experienced the longest PFS, while patients with lower baseline lymphocytes and undergoing a higher decrease of lymphocytes had the lowest PFS (mPFS 21.4 versus 11 months, respectively)....Baseline and on-treatment modifications of peripheral blood lymphocytes have independent prognostic value in HR+/HER2- aBC patients.

The present analysis aims to clarify the efficacy and safety of this treatment for hormonal receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER-) patients in the early stages of breast cancer (eBC)....In a pooled analysis, the invasive disease free survival (iDFS) was 82% (95% CI, 0.64-1.06), and the overall survival rates were consistent across the studies, with 12-month rates at 1.00 (95% CI 0.99-1.01), 24-month rates at 1.00 (95% CI 0.99-1.01), 36-month rates at 1.01 (95% CI 0.93-1.10), and 48-month rates at 1.04 (95% CI 0.91-1.19).

76 patients with advanced HR+/HER2- breast cancer were retrospectively recruited, and blood samples were collected prior to receiving chemotherapy or CDK4/6 inhibitor treatment...Patients treated with CDK4/6 inhibitors had a prolonged overall survival time compared to those treated with chemotherapies.

CDK4/6 inhibitors plus ET had a significant improvement in iDFS in stage 3 whereas there was a trend toward better iDFS in stage 2 (HzR for stage 3: 0.67, 95% CI 0.58-0.78; HzR for stage 2: 0.74, 95% CI 0.55-1.01)….Addition of CDK4/6 inhibitors to standard ET in the adjuvant treatment of HR-positive/HER2-negative early-stage BC improves iDFS.

This study aimed to evaluate the efficacy and safety of CDK4/6 inhibitors combined with endocrine therapy (ET) in patients with HR+, HER2- early breast cancer….In neoadjuvant therapy, CDK4/6 inhibitors combined with ET significantly improved CCCA compared with the control group (odds ratio = 9.00, 95% CI = 5.42-14.96, P < 0.00001)....In patients with HR+, HER2- early breast cancer, the addition of CDK4/6 inhibitors may prolong IDFS and DRFS in adjuvant therapy, especially in high-risk patients.

In the Kaplan-Meier analysis, OS rate at 3 years after first-line treatment initiation was 73.0% for ET+CDK4/6 inhibitor versus 49.1% for ET alone (log-rank p < .0001)....The findings of this real-world study demonstrate significant OS benefit associated with ET+CDK4/6 inhibitor therapy over ET alone in an older Medicare population of patients with HR+/HER2- MBC, largely consistent with the evidence from clinical trials.

For early HR+, HER2- BC, CDK4/6i combined with ET improved ORR (RR = 1.14, p = 0.05) and invasive disease free survival (iDFS) (hazard ratio = 0.87, p = 0.045)...CDK4/6i combined with ET can improve the prognosis of patients with unresectable locally advanced or metastatic HR+, HER2- BC...

The 2-year OS rate was 65% for the post-CDK4/6i era and 62% for the pre-CDK4/6i era (stratified log-rank p = 0.025). The 2-year OS for non-Hispanic White (NHW) patients improved in the post-CDK4/6i era compared to the pre-CDK4/6i era (67% vs. 63%, p = 0.033)....Our study confirms that outcomes for HR + /HER2- MBC have improved after CDK4/6i were introduced in 2015.

This study prospectively evaluated patients with HR+/HER2- aBC treated in the first- line setting with CDK4/6i + ET from February 2015 to January 2022 across 5 hospitals in Spain….The median follow-up for PFS was 18.5 m (interquartile range 10.0 – 31.7m).

Male patients with a diagnosis of HR+ and HER2-metastatic breast cancer, treated with any CDK 4–6 inhibitor...The overall response rate was 60%....In our study, we found that CDK 4–6 inhibitors are effective and safe options in men with HR+ and HER2-metastatic breast cancer as in women. Our results support the use of CDK 4–6 inhibitor-based combinations in the first-line treatment of HR+ and HER2-metastatic male breast cancer.

Among pts with HR+/HER2- disease, 50.2% received PARPi in combination with endocrine therapy and 43.5% received CDK4/6i. Median OS among pts who received CDK4/6i + endocrine therapy prior to a PARPi and those that never received a CDK4/6i was 55.1m and 36.9m, respectively (p = 0.01)....To our knowledge this is the first data set to report activity of CDK4/6i among pts with HR+/HER2- MBC who received a PARPi, with an observed 18m OS advantage compared to pts who did not receive a CDK4/6i.

We identified consecutive patients with HR+/ERBB2− MBC who received CDK4/6 inhibitors with letrozole or fulvestrant…There were 82 patients (77.3%) considered ERBB2-low expressing, which was associated with a shorter median PFS compared with 24 patients with ERBB2 IHC score of 0 (8.9 months; 95% CI, 6.49-11.30 months vs 18.8 months; 95% CI, 9.44-28.16 months; P = .01)...In multivariable analysis, ERBB2-low expression remained associated with an inferior PFS (hazard ratio [HR], 1.96; 95% CI, 1.03-3.75; P = .04)...

All analysed patients...had hormone receptor-positive, HER2-negative advanced or metastatic breast cancer, and received at least one dose of CDKI or placebo in combination with fulvestrant....The difference in estimated median overall survival was 7·1 months, favouring CDKIs. In patients who received CDKIs or placebo in combination with fulvestrant as first-line systemic endocrine therapy (two trials; n=396), the estimated HR for overall survival was 0·74 (95% CI 0·52-1·07), with a median follow-up of 39·4 months (IQR 37·0-42·2).

CDK4/6i are associated with improved outcomes in HR+/HER2- a/mBC

Patients diagnosed with stage II-III HR+/HER2- BC…Patients and oncologists were generally willing to accept increased risks of adverse events with combination CDK4/6i regimens in exchange for improved iDFS.