{"entity":{"id":"paper-loibl-geparsixto-survival-hrd-ann-oncol-2018","kind":"paper","name":"Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response-final results from GeparSixto","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2018","url":"https://doi.org/10.1093/annonc/mdy460"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30335131/"},{"label":"ClinicalTrials.gov NCT01426880","url":"https://clinicaltrials.gov/study/NCT01426880"}],"tags":["tnbc-evidence"],"related":["paper-geparsixto-lancet-oncol-2014"],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":["platinum","hrd-testing"],"targets":[],"drugs":["carboplatin","mychoice-cdx"],"companies":[],"institutions":["gbg"],"pathways":[],"terms":["hrd","pcr","hazard-ratio"],"trials":["geparsixto"],"people":["sibylle-loibl","gunter-von-minckwitz","carsten-denkert"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2018,"doi":"10.1093/annonc/mdy460","pmid":"30335131","authors":"Loibl S, Weber KE, Timms KM, et al.","paperType":"rct","findings":["Carboplatin in triple-negative disease: disease-free survival hazard ratio 0.56 (95 percent CI 0.34 to 0.93), p=0.022; overall survival gain not significant.","HRD present in 70.5 percent of 193 triple-negative tumours; HRD predicted pathological complete response (odds ratio 2.60) but not carboplatin benefit (interaction p=0.327)."],"whatItMeans":"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.","caveats":["Disease-free survival was a secondary endpoint; the trial was powered for pathological complete response.","HRD measured in 61 percent of triple-negative participants."],"changedPractice":true,"participants":315},"route":"/key-papers/paper-loibl-geparsixto-survival-hrd-ann-oncol-2018/","neighbours":{"paper":[{"id":"paper-geparsixto-lancet-oncol-2014","kind":"paper","name":"Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial","route":"/key-papers/paper-geparsixto-lancet-oncol-2014/"}],"cancer":[{"id":"tnbc-early","kind":"cancer","name":"Early triple-negative breast cancer","route":"/cancers/tnbc-early/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"hrd-testing","kind":"technology","name":"HRD & BRCA testing","route":"/technologies/hrd-testing/"},{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"mychoice-cdx","kind":"drug","name":"myChoice CDx","route":"/drugs/mychoice-cdx/"}],"institution":[{"id":"gbg","kind":"institution","name":"German Breast Group (GBG)","route":"/institutions/gbg/"}],"term":[{"id":"hazard-ratio","kind":"term","name":"Hazard ratio (HR)","route":"/terms/hazard-ratio/"},{"id":"hrd","kind":"term","name":"Homologous recombination deficiency (HRD)","route":"/terms/hrd/"},{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"}],"trial":[{"id":"geparsixto","kind":"trial","name":"GeparSixto","route":"/trials/geparsixto/"}],"person":[{"id":"carsten-denkert","kind":"person","name":"Carsten Denkert","route":"/people/carsten-denkert/"},{"id":"gunter-von-minckwitz","kind":"person","name":"Gunter von Minckwitz","route":"/people/gunter-von-minckwitz/"},{"id":"sibylle-loibl","kind":"person","name":"Sibylle Loibl","route":"/people/sibylle-loibl/"}],"journal":[{"id":"annals-of-oncology","kind":"journal","name":"Annals of Oncology","route":"/journals/annals-of-oncology/"}],"roadmap":[{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"}],"biomarker":[{"id":"hrd-positive","kind":"biomarker","name":"HRD-positive (genomic instability score)","route":"/biomarkers/hrd-positive/"},{"id":"brca-somatic","kind":"biomarker","name":"Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations","route":"/biomarkers/brca-somatic/"}]}}