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.
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.
Seventy-four of 376 screened pts were diagnosed for Lobular MBC; 48pts received PALBO-FUL, whereas 26 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, univariate 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).
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, and it allows to speculate on the best therapeutic sequence. Nevertheless, the small pts’ sample calls for a larger and adequately sized prospective validation.
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All authors have declared no conflicts of interest.