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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Monday, December 16, 2024
Joyce O’Shaughnessy, MD, of Texas Oncology-Baylor University Medical Center, Dallas, and colleagues conducted an exploratory biomarker analysis of the KEYNOTE-522 trial, which evaluated the use of chemotherapy with or without the PD-1 inhibitor pembrolizumab in patients with early-stage triple-negative breast cancer. Their findings, presented during the 2024 San Antonio Breast Cancer Symposium (SABCS; Abstract LB1-07), were specifically intended to determine the correlation between T-cell–inflamed 18-gene expression profile (GEP), non–T-cell–inflamed GEP consensus signatures, and tumor mutational burden on response and survival in this patient population.
“Pembrolizumab plus chemotherapy had an efficacy advantage vs chemo alone regardless of subgroups defined by tumor mutational burden, T-cell–inflamed GEP, and other biomarkers assessed,” concluded the investigators. “These findings may be relevant to [the] design of future studies looking to improve on immunotherapy plus chemotherapy as the standard of care.”
This phase III trial enrolled 1,172 patients with newly diagnosed, high-risk, previously untreated early triple-negative breast cancer. Whole-exome sequencing and/or RNA sequencing data were available in 946 and 904 patients to evaluate tumor mutational burden and T-cell–inflamed GEP, respectively. Cox proportional hazards regression was used to correlate event-free survival with biomarkers.
A total of 783 patients received pembrolizumab plus chemotherapy, and 389 received placebo plus chemotherapy. Of note, T-cell–inflamed GEP demonstrated a significant positive association with event-free survival and pathologic complete response in both treatment arms (P ≤ .001). Further, tumor mutational burden significantly correlated with both these parameters in the pembrolizumab cohort (P ≤ .001)—but not with event-free survival in the placebo cohort. Overall, event-free survival curves favored pembrolizumab plus chemotherapy, regardless of biomarker subgroup.
Glycolysis and proliferation correlated with pathologic complete response—but not with event-free survival—among all non–T-cell–inflamed GEP consensus signatures. Additionally, BRCA/HRD status and PTEN loss were associated with pathologic complete response in both arms, whereas HER2 gene expression was negatively associated with T-cell–inflamed GEP.
Disclosure: For full disclosures of the study authors, visit sabcs.org.
2024 San Antonio Breast Cancer Symposium
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