^
Association details:
Biomarker:HR positive
Cancer:HER2 Negative Breast Cancer
Drug Class:CDK4 inhibitor +
CDK6 inhibitor
Direction:Sensitive
Evidence:
Evidence Level:
Sensitive: B - Late Trials
Source:
Title:

Comparative Overall Survival of CDK4/6 Inhibitors Plus Endocrine Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive, HER2-negative metastatic breast cancer

Published date:
10/18/2020
Excerpt:
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.
DOI:
10.7150/jca.48944
Evidence Level:
Sensitive: B - Late Trials
Title:

Association of Cyclin-Dependent Kinases 4 and 6 Inhibitors With Survival in Patients With Hormone Receptor-Positive Metastatic Breast Cancer: A Systematic Review and Meta-analysis

Published date:
10/01/2020
Excerpt:
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.
DOI:
10.1001/jamanetworkopen.2020.20312
Evidence Level:
Sensitive: B - Late Trials
Source:
Title:

310P - Overall survival with cyclin-dependent kinase 4/6 inhibitors plus endocrine therapy in breast cancer: A meta-analysis of randomized controlled trials

Published date:
09/14/2020
Excerpt:
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),...
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Peripheral blood lymphocytes predict clinical outcomes in hormone receptor-positive HER2-negative advanced breast cancer patients treated with CDK4/6 inhibitors

Published date:
12/20/2023
Excerpt:
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.
DOI:
https://doi.org/10.1177/1758835923120
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

281P - Cyclin-dependent kinase 4/6 inhibitors combined with endocrine therapy for hormonal receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer: A meta-analysis of randomized clinical trials

Published date:
10/16/2023
Excerpt:
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).
Secondary therapy:
Hormone Therapy
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

496P - Comprehensive genomic profiling of advanced HR+/HER2- breast cancer patients using liquid biopsy

Published date:
10/16/2023
Excerpt:
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.
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Efficacy of adjuvant CDK4/6 inhibitors in Hormone Receptor-positive breast cancer: a systematic review and meta-analysis

Published date:
09/11/2023
Excerpt:
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.
DOI:
10.1080/14656566.2023.2258791
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Adjuvant and neoadjuvant therapy with cyclin-dependent kinase 4 and 6 inhibitors in hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer: a systematic review and meta-analysis

Published date:
07/11/2023
Excerpt:
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.
Secondary therapy:
Hormone Therapy
DOI:
https://doi.org/10.1530/ERC-22-0365
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Overall survival associated with CDK4/6 inhibitors in patients with HR+/HER2- metastatic breast cancer in the United States: A SEER-Medicare population-based study

Published date:
02/09/2023
Excerpt:
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.
Secondary therapy:
Hormone Therapy
DOI:
10.1002/cncr.34675
Evidence Level:
Sensitive: C3 – Early Trials
Title:

The effect and safety of CDK4/6 inhibitors combined endocrine therapy on HR+, HER2-breast cancer: a meta-analysis of randomized controlled trials

Published date:
01/18/2023
Excerpt:
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...
Secondary therapy:
Hormone Therapy; Hormone Therapy
DOI:
10.5603/EP.a2023.0007
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Racial disparities in overall survival after the introduction of cyclin-dependent kinase 4/6 inhibitors for patients with hormone receptor-positive, HER2-negative metastatic breast cancer

Published date:
12/23/2022
Excerpt:
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.
DOI:
10.1007/s10549-022-06847-2
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Efficacy analysis of CDK4/6 inhibitors in combination with endocrine therapy treatment in HR+/HER2- breast cancer according to PAM50 intrinsic subtype: primary results of SOLTI-1801_CDK-PREDICT study

Published date:
11/22/2022
Excerpt:
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).
Secondary therapy:
Hormone Therapy
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Clinical outcomes of cyclin-dependent kinase 4–6 (CDK 4–6) inhibitors in patients with male breast cancer: A multicenter study

Published date:
09/30/2022
Excerpt:
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.
DOI:
https://doi.org/10.1016/j.breast.2022.09.009
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Real-world PARPi treatment patterns and outcomes among patients with metastatic breast cancer.

Published date:
05/26/2022
Excerpt:
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.
DOI:
10.1200/JCO.2022.40.16_suppl.e13005
Evidence Level:
Sensitive: C3 – Early Trials
Title:

The Association of ERBB2-Low Expression With the Efficacy of Cyclin-Dependent Kinase 4/6 Inhibitor in Hormone Receptor–Positive, ERBB2-Negative Metastatic Breast Cancer

Published date:
11/05/2021
Excerpt:
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)...
Secondary therapy:
fulvestrant; letrozole
DOI:
10.1001/jamanetworkopen.2021.33132
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Overall survival in patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer treated with a cyclin-dependent kinase 4/6 inhibitor plus fulvestrant: a US Food and Drug Administration pooled analysis

Published date:
10/14/2021
Excerpt:
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).
Secondary therapy:
fulvestrant
DOI:
10.1016/S1470-2045(21)00472-1
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Cyclin-dependent kinase 4 and 6 inhibitors in hormone receptor-positive, human epidermal growth factor receptor-2 negative advanced breast cancer: a meta-analysis of randomized clinical trials

Published date:
02/01/2021
Excerpt:
CDK4/6i are associated with improved outcomes in HR+/HER2- a/mBC
DOI:
10.1007/s10549-020-05528-2
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

198P - Patient & oncologist preferences for adjuvant CDK4/6i therapy in HR+/HER2- early breast cancer

Published date:
09/14/2020
Excerpt:
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.