Abstract P1-19-43: Palbociclib-fulvestrant (PALBO-FUL) and everolimus-exemestane (EVE-EXE) for second line hormonal treatment (HT) of metastatic breast cancer (MBC) with …

Background: Recently, CDK4/6i proved to improve the efficacy of HT of pts affected by luminal MBC. However, the best sequence of HT is still unclear and it is still uncertain if pts with lobular histology derive the same benefit of ductal when receiving second line CDK4/6i. Particularly in lobular MBC, the dysregulation of the AKTpathway with the overexpression of cyclin E potentially represents an important mechanism of acquired resistance to HT, finally providing an intrinsic resistance to subsequent CDK4/6i. Thus, a multicentric retrospective study was conducted to determine the efficacy of PALBO-FUL versus EVE-EXE as second line HT of MBC with Lobular histology.Methods: Pts affected by Lobular MBC receiving PALBO-FUL or EVE-EXE for second line HT from 2013 to 2018 in 6 Italian centers were considered eligible. The primary endpoint was progression free survival (PFS). A propensity score (PS) adjustment for baseline characteristics was further accomplished for survival analysis. Results: Seventy-four of 376 screened pts were diagnosed for Lobular MBC; 46pts received PALBO-FUL, whereas 28 were treated with EVE-EXE, without imbalance in clinical characteristics. PFS resulted to be significantly longer for pts receiving EVE-EXE in comparison with PALBO-FUL (6.1 vs. 4.5 months, HR 0.58, 95% CI 0.35-0.96; p=0.025). Previous chemotherapy exposure resulted to be significantly associated with PFS at the multivariate analysis (HR 0.41, 95% CI 0.24-0.72, p=0.002). At the PS analysis, adjusted for previous chemotherapy exposure and synchronous/metachronous metastatic status, PFS was confirmed to be significantly longer for pts receiving EVE-EXE in comparison with PALBO-FUL (6.0 vs. 4.6 months, p=0.04)Conclusion: This retrospective real-world analysis generates the hypothesis of a potential benefit of EVE-EXE in comparison with PALBO-FUL for second line HT of MBC with Lobular histology. Nevertheless, the small pts’ sample calls for a larger and adequately sized prospective validation. However, these data allow to speculate on the best hormonal therapeutic sequence in MLBC. Indeed, in this setting a late exposure to CDK4/6i might not allow to exploit its efficacy, while once hormonal resistance is acquired the inhibition of AKT/m-TOR pathway may represent the best option. Citation Format: Armando Orlandi, Elena Iattoni, Laura Pizzuti, Agnese Fabbri, Andrea Botticelli, Carmela Di Dio, Antonella Palazzo, Giovanna Garufi, Giulia Indellicati, Daniele Alesini, Luisa Carbognin, Ida Paris, Angela Vaccaro, Luca Moscetti, Alessandra Cassano, Patrizia Vici, Valentina Magri, Giuseppe Naso, Diana Giannarelli, Paolo Marchetti, Emilio Bria, Giampaolo Tortora. Palbociclib-fulvestrant (PALBO-FUL) and everolimus -exemestane (EVE-EXE) for second line hormonal treatment (HT) of metastatic breast cancer (MBC) with lobular histology: A propensity score matched analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-43.