The introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the most relevant advance in the management of hormone receptor (HR) positive, HER2-negative metastatic breast cancer over the last few years. This meta-analysis of randomized controlled trials (RCTs) is aimed to better characterize the efficacy of CDK4/6 inhibitors in some relevant subgroups and to test heterogeneity between different compounds with a particular focus on their ability to improve overall survival (OS). Pooled estimates of hazard ratios (HRs) were computed for progression-free survival (PFS), OS, and objective response rate (ORR) analysis in predefined subgroups to better understand treatment effect concerning specific patients’ characteristics. To estimate the absolute benefit in terms of PFS, pooled survival curves were generated by pooling the data of all trials. A total of eight RCTs were included. Adding a CDK4/6 inhibitor to ET is beneficial in terms of PFS, irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the treatment-free interval (TFI). The addition of CDK4/6 inhibitors produces a significant OS improvement, both in aromatase inhibitor (AI)-sensitive (HR 0.75, 95% CI) and AI-resistant patients (HR 0.77, 95% CI [0.67–0.89]). Pooled data from each single drug show that palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68–1.02]).
PURPOSE: The introduction of CDK4/6 inhibitors plus endocrine therapy (ET) represents the most relevant advance in the management of HR-positive/HER2-negative metastatic breast cancer. We carried out a meta-analysis of randomized controlled trials (RCTs) with the aims of better characterising the efficacy of CDK4/6 inhibitors in some relevant subgroups and of testing heterogeneity between different compounds with particular focus on their ability to improve OS. METHODS: We performed a systematic literature search to identify phase II/III RCTs of CDK4/6 inhibitors plus ET in AI-sensitive and AI-resistant patients. Pooled estimates of HRs were computed for PFS, OS and ORR analysis, by using both a fixed and random effect model. Predefined subgroup analyses were performed to better understand treatment effect concerning specific patients’ characteristics. Pooled survival curves were generated by pooling the data of all trials. RESULTS: 8 RCTs were included. Adding a CDK4/6 inhibitors to ET is beneficial in terms of PFS irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the TFI. The addition of CDK4/6 inhibitors significantly improves OS in AI-sensitive (HR 0.75, 95%CI [0.63-0.89]) and AI-resistant patients (HR 0.77, 95%CI [0.67-0.89]). Pooled data from each single drug show that Palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68-1.02]). CONCLUSION: Our meta-analysis confirms the efficacy of CDK4/6 inhibitors overall and in major patients subgroups, supporting the use of CDK4/6 inhibitors plus ET as standard treatment for most HR+ MBC patients.
The addition of adjuvant chemotherapy to hormonal therapy is often considered questionable in patients with estrogen receptor-positive early breast cancer. Low risk of disease relapse after endocrine treatment alone and/or a low sensitivity to chemotherapy are reasons behind not all patients benefit from chemotherapy. Most of the patients could be exposed to unnecessary treatment- related adverse events and health care costs when treatment decision-making is based only on classical clinical histological features. Gene expression profile has been developed to refine physician’s decision-making process and to tailor personalized treatment to patients. In particular, these tests are designed to spare patients the side effects of unnecessary treatment, and ensure that adjuvant chemotherapy is correctly recommended to patients with early breast cancer. In this review, we will discuss the main diagnostic tests and their potential clinical applications (Oncotype DX, MammaPrint, PAM50/Prosigna, EndoPredict, MapQuant Dx, IHC4, and Theros-Breast Cancer Gene Expression Ratio Assay).
e12528 Background: Pts with ABC have a diverse clinical course and OS rates vary significantly among pts. New strategies had potentially changed the natural history of these pts, however data from clinical studies are still lacking and Real-World Studies (RWS) are crucial in clinical outcome evaluation. Methods: AMBRA is a longitudinal cohort study, aiming to describe the choice of first and subsequent lines of treatment in HER2-ve ABC pts receiving at least one CHT (SABCS 2016, P5-15-07 & P5-14-09) in the years 2012-2015. The present analysis is focused on the description of Progression-Free Survival (PFS) and OS according to the biologic subtype in the deceased population. So far, 791/1500 pts have been registered into the study and 255 (32.2%) are evaluable. Time to event analysis between subtypes was evaluated by Cox-Mantel Hazard Ratio and Logrank Test. DFS by Wilcoxon Rank-Sum Test. Results: Pts distribution according to molecular subtype was: Luminal A (86, 33.7%), Luminal B (107 (42.1%), TNBC (62, 24.3%). Median ages at diagnosis were 55.8, 52.9 and 55.1 years for the 3 subgroups, respectively. Mean DFS was significantly different according to the molecular subtypes: 87.28, 61.37 and 23.9 months. The difference between Luminal B and TNBC is statistically significant as well. Mean PFS of first-line therapy was 17.9 11.7 and 7.8 months respectively. Mean OS from first progression was 32.9 24.2 and 15.8 months respectively. Statistical details. Conclusions: Our data confirm in a RWS the different biological behaviour between Lum A and B. Metastatic life span is quite good for Luminal and disappointing for TNBC. Median time from last CHT and Death is quite short and similar.[Table: see text]
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