The following is a summary of “De-escalated Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer (TNBC): Impact of Molecular Markers and Final Survival Analysis of the WSG-ADAPT-TN Trial” published in the November 2022 issue of Clinical Cancer by Gluz et al.
De-escalating chemotherapy looks to be an option in selected patients within this aggressive subtype, although the ideal treatment in early triple-negative breast cancer (TNBC) is yet unknown. Numerous pro-immune variables have been identified as prognostic markers in TNBC; however, their predictive relevance on various chemotherapy methods is still debatable. Patients diagnosed with TNBC at an early stage (n=336) were randomly assigned to receive either 12 weeks of nab-paclitaxel 125 mg/m2 + gemcitabine or carboplatin d 1,8 q3w as part of the ADAPT-TN neoadjuvant multicenter phase II trial.
Patients who achieved a pathological complete response (pCR, main endpoint (ypT0/is, ypN0)) were the only ones who could forgo additional (neo-) adjuvant treatment. Gene expression of 119 genes (including PAM50 subtype) by nCounter platform and stromal tumor-infiltrating lymphocytes were used to measure secondary invasive/distant disease-free and overall survival (i/dDFS, OS) and translational research goals such as markers predictive of selection for chemotherapy de-escalation (sTIL). The 12-week pCR was linked with a higher 5y-iDFS (90.6% vs. 62.8%) 60 months into the median follow-up. The HR for this association was 0.24 (P=0.001).
Although the proportion of patients achieving pCR was greater in the carboplatin group, this did not translate into improved survival (HR, 1.04; 95% CI, 0.68-1.59). In patients who achieved a pCR, further anthracycline-containing treatment did not significantly improve their iDFS (HR, 1.29; 95% CI, 0.41-4.02). Multivariate analysis revealed that nodal status and high sTILs and pCR rate were independently linked with improved iDFS, dDFS, and OS. In early TNBC, employing the pCR rate as an early decision point for continued therapeutic escalation in conjunction with node-negative status and high sTILs is a beneficial strategy.