The addition of the LAG-3 protein eftilagimod alpha to paclitaxel led to a significant improvement in overall survival in younger patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer, according to data presented by Hans Wildiers, MD, and colleagues at the Society for Immunotherapy of Cancer (SITC) 2021 Annual Meeting (Abstract 948).
Results from a randomized phase IIb trial showed that the combination of eftilagimod and paclitaxel after endocrine-based therapy improved overall survival by nearly 8 months in patients younger than age 65 vs paclitaxel alone (P = .017). The addition of eftilagimod also increased circulating CD8-positive T cells, which was significantly correlated with overall survival, reported the study authors.
Although the combination of eftilagimod plus paclitaxel improved overall survival by nearly 3 months in the full analysis set, this increase was not found to be significant.
“The overall survival effects of adding eftilagimod to paclitaxel were significant in patients [younger] than 65, who have low monocytes and more aggressive disease,” said lead study author Dr. Wildiers, of the Department of General Medical Oncology and Multidisciplinary Breast Centre, University Hospitals Leuven, Belgium. “The combination of weekly paclitaxel and eftilagimod requires further investigation in metastatic breast cancer.”
The overall survival effects of adding eftilagimod to paclitaxel were significant in patients [younger] than 65, who have low monocytes and more aggressive disease... The combination of weekly paclitaxel and eftilagimod requires further investigation in metastatic breast cancer.— Hans Wildiers, MD
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As Dr. Wildiers explained, eftilagimod is a soluble LAG-3 protein that binds to a subset of major histocompatibility complex class II molecules and mediates activation of antigen-presenting cells followed by CD8-positive T cells. Weekly paclitaxel is a standard-of-care chemotherapy regimen employed after failure of endocrine-based therapy for metastatic breast cancer.
AIPAC (Active Immunotherapy PAClitaxel, ClinicalTrials.gov identifier NCT02614833) is a placebo-controlled, double-blind, randomized phase IIb trial that enrolled patients with HR-positive, HER2-negative metastatic breast cancer who had received prior endocrine-based therapy. Patients received paclitaxel plus eftilagimod or placebo for up to 24 weeks followed by eftilagimod or placebo for up to 52 weeks.
The primary endpoint was progression-free survival by blinded independent central review. Secondary endpoints, which included final overall survival data, were presented at SITC 2021.
A Dr. Wildiers reported, a total of 227 patients were randomly assigned in the study. Most patients were endocrine-resistant, said Dr. Wildiers, and approximately half were pretreated with a CDK4/6 inhibitor, which is an independent significant poor prognostic marker for both progression-free and overall survival.
Improvement in Overall Survival in Younger Patients
The addition of eftilagimod to paclitaxel led to a nonsignificant 2.9-month median overall survival increase in patients with HR-positive, HER2-negative metastatic breast cancer after endocrine-based therapy, Dr. Wildiers reported. The median overall survival was 20.4 months in the eftilagimod group vs 17.5 months in the placebo group (hazard ratio = 0.88, P = .197).
In a predefined univariate analysis, overall survival in patients younger than 65 was only 14.8 months in the control group compared to 22.3 months in the eftilagimod group. The difference was statistically significant (P = .017).
Eftilagimod also significantly increased circulating CD8-positive T cells, said Dr. Wildiers, which was significantly correlated with improved overall survival.
“Additional toxicity [with] eftilagimod was rare and mainly consisted of local injection site reactions,” said Dr. Wildiers, who noted that treatment-related adverse events leading to discontinuation were lower in the combination arm than in the placebo arm. “Quality of life was also higher at 6 months in the eftilagimod arm compared to the placebo [arm].”
Disclosure: Dr. Wildiers reported no conflicts of interest.