Pathological response and early survival data according to TNBCtype4 classifier in operable triple-negative breast cancer (TNBC) treated with neoadjuvant carboplatin and docetaxel

BackgroundThe identification of predictive biomarkers of response to neoadjuvant chemotherapy (NACT) is an unmet need in early-stage TNBC. Transcriptomic classification according to TNBCtype-4 classifier has shown predictive value, and we aimed to validate our previous results (Echavarria I et al, CCR 2018) in terms of response and long-term outcomes in a larger cohort.MethodsStage I-III TNBC patients were enrolled across 10 hospitals in a prospective cohort and were treated with neoadjuvant carboplatin and docetaxel for 6 cycles (NCT01560663). RNAseq was performed from FFPE core biopsies and TNBCtype-4 classification was done on the TNBCtype online tool. Response was categorized based on the Symmans residual cancer burden score.ResultsRNAseq and TNCBtype4 classification was available for 235 patients. Median age was 53 years, median tumor size 29.5 mm and 46.0% of the patients were clinically node negative. 14 patients were not evaluable for response due to incomplete axillary evaluation after NACT. Among the 221 remaining patients, the pCR rate was 47.5% (n=105). 71 (30.2%) of the patients were classified as BL1, 48 (20.4%) as BL2, 40 (17.0%) as LAR and 57 (24.3%) as M. 19 additional patients (8.1%) were considered estrogen receptor-positive (ER+) according to the TNBCtype4 classifier. pCR rate differed significantly according to TNBCtype subtyping (p=0.001), with BL1 achieving a pCR rate of 60.6%, followed by BL2 (52.1%), and M and LAR with a pCR rate of 33.3% and 32.5% respectively. Patients classified as ER+ had a pCR rate of 26.3%. This significant association was maintained in the multivariate analysis including clinicopathological factors and TILs. Although different rates of distant relapse were observed across subgroups, they did not reach statistical significance with the current follow-up (p=0.09). With a median follow-up of 53 months, 3 year-distant disease-free survival (dDFS) was 89.4% for BL1, 82.3% for BL2, 83.9% for M and 73.2% for LAR (p=0.13).ConclusionsTNCBtype-4 classifier significantly predicts pCR rate to NACT in operable TNBC patients. A non-significant trend towards different dDFS was observed, although longer follow-up is needed.Clinical trial identificationNCT01560663.Legal entity responsible for the studyHospital General Universitario Gregorio Marañon.FundingInstituto de Salud Carlos III PI12/02684, PI15/00117, PI18/01775 Fondo Europeo de Desarrollo Regional.DisclosureJ.Á. García Saenz: Financial Interests, Personal, Invited Speaker: Novartis, Celgene, Eli Lilly, Eisai; AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Other, travel support: Novartis, Roche, Pfizer. All other authors have declared no conflicts of interest. BackgroundThe identification of predictive biomarkers of response to neoadjuvant chemotherapy (NACT) is an unmet need in early-stage TNBC. Transcriptomic classification according to TNBCtype-4 classifier has shown predictive value, and we aimed to validate our previous results (Echavarria I et al, CCR 2018) in terms of response and long-term outcomes in a larger cohort. The identification of predictive biomarkers of response to neoadjuvant chemotherapy (NACT) is an unmet need in early-stage TNBC. Transcriptomic classification according to TNBCtype-4 classifier has shown predictive value, and we aimed to validate our previous results (Echavarria I et al, CCR 2018) in terms of response and long-term outcomes in a larger cohort. MethodsStage I-III TNBC patients were enrolled across 10 hospitals in a prospective cohort and were treated with neoadjuvant carboplatin and docetaxel for 6 cycles (NCT01560663). RNAseq was performed from FFPE core biopsies and TNBCtype-4 classification was done on the TNBCtype online tool. Response was categorized based on the Symmans residual cancer burden score. Stage I-III TNBC patients were enrolled across 10 hospitals in a prospective cohort and were treated with neoadjuvant carboplatin and docetaxel for 6 cycles (NCT01560663). RNAseq was performed from FFPE core biopsies and TNBCtype-4 classification was done on the TNBCtype online tool. Response was categorized based on the Symmans residual cancer burden score. ResultsRNAseq and TNCBtype4 classification was available for 235 patients. Median age was 53 years, median tumor size 29.5 mm and 46.0% of the patients were clinically node negative. 14 patients were not evaluable for response due to incomplete axillary evaluation after NACT. Among the 221 remaining patients, the pCR rate was 47.5% (n=105). 71 (30.2%) of the patients were classified as BL1, 48 (20.4%) as BL2, 40 (17.0%) as LAR and 57 (24.3%) as M. 19 additional patients (8.1%) were considered estrogen receptor-positive (ER+) according to the TNBCtype4 classifier. pCR rate differed significantly according to TNBCtype subtyping (p=0.001), with BL1 achieving a pCR rate of 60.6%, followed by BL2 (52.1%), and M and LAR with a pCR rate of 33.3% and 32.5% respectively. Patients classified as ER+ had a pCR rate of 26.3%. This significant association was maintained in the multivariate analysis including clinicopathological factors and TILs. Although different rates of distant relapse were observed across subgroups, they did not reach statistical significance with the current follow-up (p=0.09). With a median follow-up of 53 months, 3 year-distant disease-free survival (dDFS) was 89.4% for BL1, 82.3% for BL2, 83.9% for M and 73.2% for LAR (p=0.13). RNAseq and TNCBtype4 classification was available for 235 patients. Median age was 53 years, median tumor size 29.5 mm and 46.0% of the patients were clinically node negative. 14 patients were not evaluable for response due to incomplete axillary evaluation after NACT. Among the 221 remaining patients, the pCR rate was 47.5% (n=105). 71 (30.2%) of the patients were classified as BL1, 48 (20.4%) as BL2, 40 (17.0%) as LAR and 57 (24.3%) as M. 19 additional patients (8.1%) were considered estrogen receptor-positive (ER+) according to the TNBCtype4 classifier. pCR rate differed significantly according to TNBCtype subtyping (p=0.001), with BL1 achieving a pCR rate of 60.6%, followed by BL2 (52.1%), and M and LAR with a pCR rate of 33.3% and 32.5% respectively. Patients classified as ER+ had a pCR rate of 26.3%. This significant association was maintained in the multivariate analysis including clinicopathological factors and TILs. Although different rates of distant relapse were observed across subgroups, they did not reach statistical significance with the current follow-up (p=0.09). With a median follow-up of 53 months, 3 year-distant disease-free survival (dDFS) was 89.4% for BL1, 82.3% for BL2, 83.9% for M and 73.2% for LAR (p=0.13). ConclusionsTNCBtype-4 classifier significantly predicts pCR rate to NACT in operable TNBC patients. A non-significant trend towards different dDFS was observed, although longer follow-up is needed. TNCBtype-4 classifier significantly predicts pCR rate to NACT in operable TNBC patients. A non-significant trend towards different dDFS was observed, although longer follow-up is needed.