KI67 AND CYCLIN-DEPENDENT KINASE 4/6 INHIBITORS EFFICACY FOR METASTATIC BREAST CANCER

Introduction: Ki67 index is a predictive biomarker for non-metastatic luminal breast cancer treated with hormonal therapy (HT). Recently, although not statistically proven, a discussion of a potential survival improvement with adjuvant abemaciclib in a subgroup of patients with tumors with Ki67 > 20% was raised by the FDA. Data on the impact of Ki67 on oncological outcomes for metastatic breast cancer patients treated with cyclin-dependent kinase 4/6 inhibitors (iCDK) are scarce. Objective: To evaluate the impact of Ki67 on progression-free survival (PFS) of luminal metastatic breast cancer patients treated with iCDK + hormonal therapy (HT) in first line. Methods: Retrospective unicentric analysis of luminal HER2 negative metastatic breast cancer patients, treated in first line with iCDK + HT (tamoxifen/aromatase inhibitor/fulvestrant ± ovarian suppression therapy). Progression-free survival was defined as the time from iCDK initiation to disease progression or death by any cause. Three cutoffs of Ki67 were used for the primary endpoint analysis: 10%, 15% and 20% (≤ versus > for all). The Ki67 from the most recent biopsy prior to iCDK initiation was considered. Time-to-event variables were described by Kaplan-Meier curves and compared by Log-rank test and Cox regression. P<0.05 were statistically significant. Results: From 2016 to 2021, 117 patients were included. The median follow-up was 22 months (95%CI: 15.7-28.3). The median age was 55 (30-80) years old; 61.5% were postmenopausal women and 35% de novo metastatic. iCDK used: palbociclib (43.6%), ribociclib (27.4%) and abemaciclib (23.9%); and HT used: aromatase inhibitors (61.0%), fulvestrant (31.6%), tamoxifen (6.4%). 41% of Ki67 were from primary tumor and 59% from metastasis tissue. Regardless of the Ki67 cutoff, PFS did not differ among lower and higher levels: 21 vs 30m for Ki67 < and > 20%, respectively (p=0.87); and 21 vs 27m for both < and > 15% and 10% (p=0.93 and 0.77). PFS was numerically improved for luminal A – Ki67 < 15% + progesterone receptor > 20% (23m vs not reached; HR: 0.17, 95%CI: 0.02-1.23; p=0.02) and estrogen-receptor (ER) non-low – ER > 10% (4 vs 27m, HR:0.45, 95%CI: 0.141.45; p=0.16) tumors. Visceral metastasis and HT with fulvestrant were independently associated with inferior PFS in multivariable analysis. Conclusion: Albeit the Ki67 index is a valuable biomarker for breast cancer, no impact on oncological outcomes during first line iCDK therapy was found in this study.