Study findings reveal HER2-low expression did not significantly impact patients with estrogen receptor (ER)-positive, HER2-negative breast cancer treated with cyclin-dependent kinase (CDK) 4 and 6 inhibitors.

These findings were presented at the 2022 ASCO Annual Meeting by lead author, Laura Sabina Lapuchesky, Instituto Alexander Fleming, Cramer 1180, Buenos Aires, Argentina.

“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,” wrote Dr Lapuchesky and colleagues.

“There is limited and conflicting evidence regarding the efficacy of [CDK 4/6] inhibitors in patients with ER-positive and HER2-low tumors,” they continued.

In this study, patients with ER-positive/HER2-negative advanced breast cancer treated with CDK 4/6 inhibitors plus endocrine therapy from May 2015 to February 2020 were retrospectively selected. Researchers compared 2 cohorts of patients: HER2-0 (IHC score) and HER2-low (HER2 IHC score 1+ and 2+) tumors.

Log-rank test was used to compare progression-free survival (PFS) and overall survival (OS). Cox regression model was used to determine the prognostic value of HER2-low expression.

A total of 186 patients (median age, 55 years) were included in the study; 67.8% had an ECOG performance score of 0. There were 155 (83.3%) tumors that were progesterone receptor-positive. Overall, 27 patients (14.5%) had de novo metastatic disease, 68 (36.6%) had only bone metastases, and 69 (37.1%) had visceral disease.

The majority (n = 131; 70.4%) of patients received CDK4/6 inhibitors and endocrine therapy in the first-line treatment setting. Of the patients included in the study, 161 (86.6%) received palbociclib, 23 (12.4%) received ribociclib and 2 (1.08%) received abemaciclib.

Overall, 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. The median PFS among patients with HER2-0 disease was 19 months (95% confidence interval [CI], 13.9 to 24.1) and 15.6 months (95% CI, 11.1-20.0) among patients with HER2-low disease (P = .074).

In patients treated with CDK 4/6 in the first-line setting, there wre no statistically significant differences in PFS and OS observed between HER2-0 and HER2-low patients (PFS HR, 0.73; 95% CI, 0.47 to 1.13; P = .160; and OS HR, 1.04; 95% CI, 0.51 to 2.14; P = .909).

“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,” concluded Dr Lapuchesky and colleagues.

Source:

Lapuchesky LS, Bortz M, Waisberg F, et al. CDK4/6 inhibitors outcomes in patients with advanced breast cancer based on HER2-low expression. Presented at: ASCO Annual Meeting; June 3-7, 2022. Chicago, IL, and virtual. Abstract 1056.