Photo Credit: Nemes Laszlo

Findings from KEYNOTE-522 in high-risk, early-stage triple-negative breast cancer (TNBC) indicated that tumor mutational burden (TMB) and various biomarkers, including T cell-inflamed gene expression profile (Tcell_infGEP) were positively associated with improved pathological complete response (pCR) and event-free survival (EFS), regardless of pembrolizumab addition.

The phase 3, randomized, placebo-controlled KEYNOTE-522 trial (NCT03036488) aimed to assess the effectiveness of neoadjuvant and adjuvant pembrolizumab combined with chemotherapy in patients with newly diagnosed, untreated, high-risk, early-stage TNBC. Previously, neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab has significantly improved in pCR, EFS, and overall survival (OS)^1-3. Joyce O’Shaughnessy, MD, from Baylor University Medical Center, Texas, presented the exploratory biomarker analysis results that evaluated associations between potential biomarkers for pembrolizumab and pCR and EFS using a pre-specified statistical analysis plan⁴.

The study randomly assigned 1,172 participants to receive either pembrolizumab or placebo. Baseline tumor biopsies were used for biomarker evaluation. The key objectives were determining the association of Tcell_infGEP, TMB, and non-Tcell_infGEP consensus signatures with pCR and EFS. Secondary objectives included additional biomarkers, such as TNBC molecular subtypes, homologous recombination deficiency (HRD) status, HER2 gene expression, and signature and PTEN loss signature.

Several biomarkers, including Tcell_infGEP, were positively associated with higher pCR rate and longer EFS, with or without the addition of pembrolizumab. In the placebo plus chemotherapy arm, a higher TMB was positively associated with pCR but not EFS. “Notably, the number of participants with high TMB in this TNBC population was relatively small,” remarked Dr. O’Shaughnessy. Among the non-Tcell_infGEP consensus signatures, glycolysis and proliferation were positively associated with pCR, but not EFS, in both treatment arms. PTEN loss signature and HRD status were positively associated with pCR in both arms, while TNBC molecular subtypes showed a modest association with both pCR and EFS.

“Pembrolizumab plus chemotherapy had an efficacy advantage versus chemotherapy alone in subgroups defined by various potential biomarkers, including Tcell_infGEP, non-Tcell_infGEP consensus, TMB, TNBC molecular subtypes, and HRD status,” concluded Dr. O’Shaughnessy.

Medical writing support was provided by Kulsoom Abdul.

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