medwireNews: RNA-based tumor cell proliferation and immune scores could help to identify triple-negative breast cancer (TNBC) patients who are likely to respond to neoadjuvant chemotherapy, suggests a secondary analysis of the BrighTNess trial.
The phase 3 study previously showed that patients with stage II–III disease could benefit from combining carboplatin with neoadjuvant paclitaxel, although the further addition of the PARP inhibitor veliparib to the carboplatin-containing regimen did not appear to offer a significant advantage.
The current analysis, reported in JAMA Oncology, aimed “to evaluate the association of molecular subtype, tumor proliferation, and immunophenotype with response” among the 482 participants with available RNA sequencing data from a pretreatment biopsy.
Participants with basal-like TNBC, based on the molecular PAM50 subtype classification, had a better pathologic complete response (pCR) rate than those with nonbasal-like disease, but the between-group differences were statistically significant only in the overall study population (52.3 vs 35.4%) and among those who received carboplatin, with or without veliparib, plus paclitaxel (58.1 vs 40.0%).
The investigators stress, however, that there was no significant difference in the benefit offered by the addition of carboplatin between the basal-like and nonbasal groups.
Multivariable analysis accounting for factors such as lymph node and BRCA status identified a significant association between pCR and the GeparSixto immune score and PAM50 proliferation score, with hazard ratios of 0.36 and 0.62, respectively. Moreover, in the overall study population, patients with scores above the median for both signatures had a significantly higher pCR rate than those with both scores below the median, at 67% and 34%, respectively.
The findings were similar in the combined carboplatin and control groups, with pCR rates for individuals with both scores above versus below the medians of 72% versus 41% and 52% versus 13%, respectively.
Otto Metzger Filho (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and colleagues also reported an exploratory gene expression analysis pointing to a greater benefit from the addition of carboplatin in patients harboring tumors with high CD8+ T-cell infiltration. By contrast, higher levels of total macrophage and M2 macrophage infiltration appeared to be associated with an increased likelihood of response to paclitaxel alone.
However, these immunophenotype data “require validation using pathology-based markers,” cautions the team.
“Taken together, these study findings suggest that RNA-based metrics should be informative in the identification of subsets of patients most likely to benefit from novel therapies,” say Metzger Filho et al.
“As the field of TNBC evolves, it will be important to understand if immune checkpoint inhibitors will improve pCR rates among those patients less likely to respond to standard [neoadjuvant chemotherapy] (ie, with low proliferation and/or low immune scores).”
They continue: “More importantly, it will be critical to define the subset of patients likely to be cured with standard chemotherapy and to concentrate efforts on patients known to have an unfavorable long-term outcome.”
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JAMA Oncol 2021; doi:10.1001/jamaoncol.2020.7310