The GeparNuevo trial sheds light on the role of RNA expression from peripheral immune cells in predicting treatment outcomes.
The phase 2 GeparNuevo trial (NCT02685059) has demonstrated that the addition of durvalumab to anthracycline/taxane-based neoadjuvant chemotherapy improved pathologic complete response (pCR) rate and survival in patients with triple-negative breast cancer. In a subproject, blood samples from patients were collected to explore biomarkers that predict patients who may benefit from neoadjuvant immune checkpoint therapy compared with standard neoadjuvant therapy. Hanna Huebner, PhD, presented the first results at the 2023 ASCO Annual Meeting, held June 2-6 in Chicago.
Blood samples at baseline from 117 patients enrolled in the GeparNuevo trial were available for RNA testing (n=63 treated with durvalumab/chemotherapy; n=54 treated with placebo/chemotherapy). Based on the RNA expression, 16 different immune cell scores were defined, as well as 26 immune signaling scores. Correlation of these scores with treatment outcome parameters (ie, pCR, distant disease-free survival [DDFS]) was analyzed, as well as any correlation of expression of 31 individual genes with these outcome parameters.
Expression of one immune cell score (ie, mast cells) and five individual genes (CCL3, DPP4, ITGA4, MYC, and TIMP1) were significantly associated with pCR. For example, patients with low CCL3 or high ITGA4 expression benefitted from durvalumab (ie, higher pCR rate) whereas in patients with high expression of CCL3 or low expression of ITGA4 before neoadjuvant, pCR was lower with durvalumab compared with placebo. On the other hand, high expression of DPP4 or low expression of TIMP1 was associated with a higher pCR regardless of the treatment arm (ie, durvalumab or placebo added to the neoadjuvant treatment).
With respect to DDFS, two immune cell scores, one immune signaling score, and the expression of 31 individual genes appeared to be significantly associated with DDFS. For example, a high Treg cell score was associated with a longer DDFS, both for placebo- and durvalumab-treated patients. Patients with low AKT signaling scores benefitted from durvalumab, whereas in patients with a high AKT signaling score durvalumab did not improve DDFS. Likewise, low expression of CDK2, high expression of MYC, and high expression of TIPM1 were associated with a DDFS benefit of durvalumab.
Based on these results, Dr. Huebner concluded that “in patients with triple-negative breast cancer, RNA expression levels from peripheral immune cells could enable differentiation between patients who might benefit from neoadjuvant immune checkpoint therapy compared with standard therapy. However, further research is necessary to validate and expand upon these initial results.”
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