Biomarkers for response to immunotherapy in triple-negative breast cancer: Differences between survival and pCR biomarkers

Autor: Carsten Denkert, Andreas Schneeweiss, Julia Rey, Thomas Karn, Michael Braun, Jens Bodo Huober, Hans-Peter Sinn, Dirk Michael Zahm, Claus Hanusch, Frederik Marmé, Jenny Furlanetto, Joerg Thomalla, Jens U. Blohmer, Marion van Mackelenbergh, Peter Staib, Christian Jackisch, Peter A. Fasching, Bruno Valentin Sinn, Michael Untch, Sibylle Loibl
Rok vydání: 2022
Předmět:
Zdroj: Journal of Clinical Oncology. 40:583-583
ISSN: 1527-7755
0732-183X
Popis: 583 Background: Immunotherapy is entering clinical practice as a promising new neoadjuvant therapeutic approach in triple-negative breast cancer, and it is important to identify biomarkers to focus this therapy on those patients that have the highest benefit. Interestingly, an improved survival outcome is observed in pCR and non-pCR patients, which raises the hypothesis that biomarkers might also be different for pCR prediction as well as prognosis. In this study, we investigated this hypothesis in the neoadjuvant GeparNuevo trial. Methods: A total of 174 patients were randomized to receive neoadjuvant chemotherapy with durvalumab vs. placebo. HTG EdgeSeq mRNA analysis was performed for a total of 2549 genes in 162 pretherapeutic core biopsies. In addition, tumor-infiltrating lymphocytes (stromal and intratumoural) as well as PD-L1 protein expression was evaluated by IHC. We systematically compared the distant disease-free survival (DDFS) of 5 predefined gene signatures (including the GeparSixto immune signature) as well as 12 single mRNA markers identified in previous projects between treatment arms using univariate Cox proportional-hazard regression analyses. In addition, exploratory biomarker analyses were performed. Results: The PSIP1 gene expression (per 1 unit hazard ratio [HR]: 0.58 95%CI 0.41-0.83; p=0.002), TAP1 (per 1 unit HR: 0.68 95%CI 0.48-0.95; p=0.025) as well as stromal TILs (sTILs) (per 10% HR: 0.73 95%CI 0.56-0.95; p=0.019) were significant for improved DDFS in the complete cohort. In the placebo arm PSIP1 (HR 0.50 95%CI 0.29-0.87; p=0.014) as well as sTILs (HR 0.73 95%CI 0.53-0.99; p=0.044) were significant for improved DDFS. In the durvalumab arm, the gene expression of PSIP1 (HR 0.54 95%CI 0.31-0.94; p=0.029), PD-L1/CD274 (per 1 unit HR: 0.41 95%CI 0.21-0.77; p=0.006), CD38 (per 1 unit: HR 0.52 95%CI 0.29-0.92; p=0.026) as well as the GeparSixto immune signature (per 1 unit HR: 0.51 95%CI 0.27-0.97; p=0.041) were significant for improved DDFS, with a positive test for interaction with treatment arm for PD-L1/CD274 (interaction p=0.020). Additional analyses, including multivariate Cox regressions for DDFS as well as systematic comparisons for biomarkers for DDFS and for pCR, will be presented. Conclusions: Our analysis suggests that biomarkers for immune response are linked to improved survival with neoadjuvant durvalumab therapy and that in this setting, survival biomarkers are not identical to pCR biomarkers. The results are a basis for a further dissection of the contribution of pCR to survival effects of immunotherapy.
Databáze: OpenAIRE
Externí odkaz: