Abstract P2-08-34: The network metanalysis of data from PALOMA 2, MONALEESA 2, MONARCH 3, FALCON, SWOG and FACT trials: Progression free survival (PFS) benefit from first-line endocrine-based therapies in postmenopausal women with HR+ HER2- metastatic breast cancer (MBC) according to different prognostic subgroups
Authors: Rossi V , Giannarelli D , Berchialla P , Montemurro F , Ferretti G , Nistico' C , Vigna L , Cognetti F , Fabi A 
Published: May 2019

Abstract
Background
The three classes of Cycline Dependend Kinase (CDK) 4/6 inhibitors, Palbociclib (P), Ribociclib (R) and Abemaciclib (A), in combination with non-Steroidal Aromatase Inhibitors (nSAIs) showed improvement on Progression Free Survival (PFS) in patients with HR+/HER2- MBC compared to AIs monotherapy.
Fulvestrant (F) also showed a PFS benefit over AIs in first-line setting of endocrine naive patients (pts) which was even greater in pts whithout visceral disease.
The absence of direct comparison between F and CDK 4/6 combination therapies and their less favorable toxicity profile generated great interest in the identification of a specific subgroup of pts based on clinical and pathological factors for decision-making in the use of endocrine monotherapy.
This analysis combines data from six randomized phase III trials investigating the role of endocrine-based therapies in the first-line setting of HR+/HER2- MBC to identify clinical factors in the choice among available drugs.
Methods
A Bayesian network meta-analysis was carried out for PFS; Hazard Ratio (HR) and 95% CI were reported. Potential treatment effect modifying covariates were investigated using sub-group analysis, stratifying by age, ECOG, ethnicity, prior chemotherapy or endocrine therapy exposure, measurable disease at the time of metastasis occurrence, visceral or bone only disease, time from the initial diagnosis of breast cancer to the metastasis onset. Data analysis was performed using R Statistical Software version 3.5.0
Results
In the absence of direct comparison between CDK 4/6 inhibitors + nAIs and F endocrine-based therapies, all these therapeutic options resulted in significant PFS benefit compared to nAIs monotherapy (HR: 0.74; 95% CI 0.67-0.80). However, among the three classes of CDK 4/6 inhibitors and F a significant longer PFS was observed according to some clinical-pathological factors as followed reported: from P + nAIs in “bone only” disease (HR 0.47; CI 0.25-0.86); from A + nAis in “de novo” subgroup (HR 0.60; CI 0.37-0.97), in “Asian” population (HR 0.37; CI 0.16-0.85) and “non visceral” disease (HR 0.48 CI 0.25-0.89); from R + nAIs in “de novo” subgroup (HR 0.55; CI 0.32-0.95) and in “visceral” disease (HR 0.66 CI 0.45-0.96); from all the three combination strategies (A, P and R) in “prior endocrine” exposure subgroup (HR 0.47 CI 0.25-0.87; HR 0.60 CI 0.45-0.80; HR 0.64 CI 0.41-1.0, respectively). Even though no significant PFS benefit was observed in the remaining subgroups, combined CDK 4/6 strategies appeared more effective than F according to relative HR.
Conclusions
CDK 4/6 inhibitors endocrine-based therapies as first-line treatment for postmenopausal women with HR+/HER2- MBC showed PFS improvement, regardless of prognostic subgroup and additionally advantage was emerged by indirect comparison with F. Further direct comparative studies are needed to explore greater benefits from different therapeutic options.
Citation Format: Rossi V, Giannarelli D, Berchialla P, Montemurro F, Ferretti G, Nistico' C, Vigna L, Cognetti F, Fabi A. The network metanalysis of data from PALOMA 2, MONALEESA 2, MONARCH 3, FALCON, SWOG and FACT trials: Progression free survival (PFS) benefit from first-line endocrine-based therapies in postmenopausal women with HR+ HER2- metastatic breast cancer (MBC) according to different prognostic subgroups [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-34.