CDK4/6 inhibitors outcomes in patients with advanced breast cancer based on HER2-low expression.

1056 Background: HER2-low expression, defined as HER2 immunohistochemistry (IHC) score of 1+ or 2+ with negative in situ hybridization assay (FISH), accounts for 50% of breast cancers. There is limited and conflicting evidence regarding the efficacy of cyclin-dependent kinase (CDK) 4 and 6 inhibitors in patients with ER+ and HER2-low tumors. This study aimed to investigate the prognostic value of HER2-low expression in patients with ER+/HER2-negative advanced breast cancer treated with CDK 4/6 inhibitors. Methods: We retrospectively selected consecutive patients with ER+/HER2-negative advanced breast cancer treated with CDK 4/6 inhibitors plus endocrine therapy in our institution from May 2015 to Feb 2020. Two cohorts were compared, including HER2-0 (IHC score) and HER2-low (HER2 IHC score 1+ and 2+ [negative FISH]) tumors. Comparisons in progression-free survival (PFS) and overall survival (OS) were performed using a log-rank test. The prognostic value of HER2-low was investigated by the Cox regression model. Results: Among the 186 patients included, median age at treatment was 55 (r 27-84), and majority had ECOG 0 (126, 67.8%). Progesterone receptor was positive in 155 (83.3%) tumors. Of note, most patients received CDK4/6 inhibitors and endocrine therapy as first-line setting (131, 70.4%). Mostly received palbociclib (161, 86.6%), while ribociclib and abemaciclib were used in 23 (12.4%) and 2 (1.08%) patients, respectively. Overall, 27 patients (14.5%) had de novo metastatic disease, 68 (36.6%) had only bone metastases, and 69 (37.1%) had visceral disease. Of the total population, 64 (34.4%) tumors were HER2-low (43 [23.1%] HER2-1+, and 21 [11.3%] HER2-2+), and 122 (65.6%) were HER2-0. Median PFS among patients with HER2-0 and HER-low were 19 mo. (95% CI, 13.9-24.1), and 15.6 mo. (95% CI, 11.1-20.0), p = 0.074, respectively. In patients treated with CDK 4/6 in the first-line setting, no statistically significant differences were observed in terms of PFS and OS between HER2-0 and HER2-low (PFS HR 0.73 [95% CI, 0.47-1.13; p = 0.160], and OS HR 1.04 [95% CI, 0.51-2.14; p = 0.909]). Conclusions: In our study, HER2-low expression did not show a statistically significant impact on patients with ER+/HER2-negative advanced breast cancer treated with CDK 4/6 inhibitors. Our study supports the necessity of real-world evidence and the design of pooled analysis to understand the real implication of this biomarker in patients with ER+/HER2-negative tumors.