Prognostic Value of the Baseline Systemic Immune-Inflammation Index in HER2-Positive Metastatic Breast Cancer: Exploratory Analysis of Two Prospective Trials

Purpose: The systemic immune-inflammation index (SII) is a hematological marker that reflects the immune status of the body. This study was designed to evaluate the prognostic significance of the baseline SII in HER2-positive metastatic breast cancer (MBC) patients receiving chemotherapy plus trastuzumab without or with pertuzumab.

Methods: Data were collected from 774 patients from the CLEOPATRA trial, 196 patients from the H0648G trial, and 229 patients from six clinical centers in China. Patients were divided into the low and high SII subgroups according to the median SII value. The inverse probability of treatment weighting (IPTW) method was used to control bias. Associations between the SII and progression-free survival (PFS) and overall survival (OS) were analyzed.

Results: In the CLEOPATRA trial, a lower SII was associated with better PFS (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.04-1.65, P = 0.02) and OS (HR 1.42, 95% CI 1.07-1.88, P = 0.02) in the trastuzumab and docetaxel groups, as well as improved PFS in the trastuzumab and pertuzumab and docetaxel groups (HR 1.39, 95% CI 1.10-1.77, P < 0.01) after IPTW. In the H0648G trial, a lower SII was associated with better PFS (P = 0.04) and OS (P = 0.02) in HER2-positive MBC patients receiving trastuzumab-based therapy. According to real-world data, a lower SII predicted an improvement in PFS for patients treated with docetaxel plus trastuzumab without or with pertuzumab (P = 0.02 and 0.01, respectively).

Conclusions: A low baseline SII is associated with better survival outcomes among HER2-positive MBC patients receiving trastuzumab-based first-line therapy.