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The final GeparSixto report: adding carboplatin before surgery cut relapse in triple-negative disease by 44 percent, and a DNA-repair deficiency score predicted which tumours would disappear, though it did not predict who gained from the platinum.
Loibl, Weber, Timms, Elkin and colleagues report survival and homologous recombination deficiency (HRD) analyses from GeparSixto, in which patients received paclitaxel plus non-pegylated liposomal doxorubicin with or without carboplatin; median follow-up was 47.3 months. Disease-free survival was significantly better with carboplatin in triple-negative disease (hazard ratio 0.56, 95 percent confidence interval 0.34 to 0.93, p=0.022); the overall survival improvement was not significant, and carboplatin did not help HER2-positive tumours. HRD (score 42 or more and/or tumour BRCA mutation) was measured in 193 of 315 triple-negative participants and present in 136 (70.5 percent), of whom 82 (60.3 percent) had a high score without a BRCA mutation. HRD independently predicted pathological complete response (odds ratio 2.60, p=0.008); carboplatin raised the response rate from 33.9 to 63.5 percent in HR-deficient tumours (p=0.001) and from 20.0 to 29.6 percent in non-deficient tumours (p=0.540; interaction p=0.327), and from 31.7 to 63.2 percent in high-HRD tumours without BRCA mutation. Disease-free survival improved with carboplatin in both deficient (0.49) and non-deficient (0.44) tumours.
The survival evidence behind platinum in early triple-negative disease, and the first large demonstration that most triple-negative tumours are DNA-repair deficient whether or not BRCA is mutated, which is why HRD scores have not become a platinum selection test.
Shares Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial, GeparSixto, Pathologic complete response (pCR), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem and the tag tnbc-evidence.
Shares Sibylle Loibl, Annals of Oncology, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Platinum agents and the tag tnbc-evidence.
Shares Annals of Oncology, Pathologic complete response (pCR), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Platinum agents and the tag tnbc-evidence.
Shares Sibylle Loibl, Annals of Oncology, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Hazard ratio (HR), Annals of Oncology, BRCA1 / BRCA2 (HRD), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem and the tag tnbc-evidence.
Shares Hazard ratio (HR), Pathologic complete response (pCR), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Sibylle Loibl, Annals of Oncology, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Pathologic complete response (pCR), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Early triple-negative breast cancer, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.