210P Prognostic value of HER2-low status in metastatic breast cancer (mbc) patients treated with I line CDK 4/6 inhibitors (CDK 4/6i): A real-word analysis of the GIM14/BIOMETA study

The combination of CDK 4/6i and endocrine treatment is the standard first-line treatment in patients with hormone receptor-positive/HER2-negative mBC. It is still unclear whether HER2-low status has a prognostic impact in this patients' subgroup. Data of eligible patients were retrieved within the Italian retrospective/prospective multicentric GIM14/BIOMETA study (NCT02284581). In this analysis, we included patients who received CDK 4/6i in I line. HER2 status was assessed locally on advanced stage biopsy if available and if not, on the primary tumour. Tumour characteristics and survival outcomes [progression-free survival (PFS) and overall survival (OS)] were compared between patients with HER2-low and HER2-zero tumours. Overall, 701 pts were eligible for this analysis, of whom 531 patients (75.7%) were enrolled in the prospective cohort. 365 pts (52%) had HER2-zero tumours, 336 (48%) had HER2-low tumours. No difference in tumour characteristic were observed between patients with HER2-zero or HER2 low-tumours. After a median follow-up of 24.8 months, no significant differences were found in terms of PFS (median PFS 2.18 years (IQR 1.07-NR) and 2.30 years (IQR 1.01-5.37) in HER2 0 and HER2-low, respectively) (p=0.972) or OS (median OS beyond 5 years for both groups) (p=0.398). Matched advanced stage and primary tumour biopsies were available for 231 subjects. 65 out of 149 HER2-zero primary tumours turned into HER2-low at the advanced stage biopsy. Among 82 HER2-low primary breast cancers, 29 were classified as HER2-zero at the biopsy performed in the metastatic setting. Among those who experienced disease progression, after CDK 4/6i 40% of patients received chemotherapy (more frequently capecitabine or taxane plus bevacizumab), 36% endocrine treatment (the majority exemestane+ everolimus or fulvestrant), 2% PARP inhibitors or alpelisib, and 9% CDK 4/6i beyond progression. In 13% of cases II line data were not reported. No significant difference in terms of survival outcomes were found between patients affected by HER2-zero and HER2-low breast cancer treated in I line with CDK 4/6i.