{"entity":{"id":"geparsixto","kind":"trial","name":"GeparSixto","aka":["GBG 66"],"tldr":"GeparSixto showed that adding carboplatin to chemotherapy given before surgery made triple-negative breast tumours disappear completely far more often, and in longer follow-up cut relapses, which put platinum into the standard neoadjuvant regimen for this type.","summary":"GeparSixto randomised 595 women with early triple-negative or HER2-positive breast cancer to 18 weeks of weekly paclitaxel and non-pegylated liposomal doxorubicin, with bevacizumab for triple-negative and trastuzumab plus lapatinib for HER2-positive disease, with or without weekly carboplatin. The primary endpoint was pathological complete response.\n\nCarboplatin increased the pathological complete response rate in triple-negative disease, and in longer follow-up improved disease-free survival in that group, but did not help HER2-positive disease and added haematological toxicity. Together with CALGB 40603 and later BrighTNess it established carboplatin as part of neoadjuvant chemotherapy for triple-negative breast cancer, the backbone that KEYNOTE-522 then added pembrolizumab to.","status":"positive","asOf":"2026-09-17","links":[{"label":"ClinicalTrials.gov NCT01426880","url":"https://clinicaltrials.gov/study/NCT01426880"},{"label":"GeparSixto survival and HRD analysis (Annals of Oncology 2018)","url":"https://doi.org/10.1093/annonc/mdy460"}],"tags":["subtype-trials"],"related":[],"cancers":["tnbc-early","tnbc","breast-cancer"],"sections":[],"technologies":["cytotoxic-chemotherapy","platinum"],"targets":[],"drugs":["carboplatin","paclitaxel","doxorubicin","bevacizumab","trastuzumab","lapatinib"],"companies":["gbg"],"institutions":[],"pathways":[],"terms":[],"trials":["brightness","calgb-40603","keynote-522"],"people":["gunter-von-minckwitz"],"bottlenecks":[],"keyPapers":["paper-hahnen-geparsixto-germline-brca-jama-oncol-2017","paper-loibl-geparsixto-survival-hrd-ann-oncol-2018","paper-geparsixto-lancet-oncol-2014"],"journals":[],"dependsOn":[],"notes":["Survival analysis (Annals of Oncology 2018, median follow-up 47.3 months): disease-free survival hazard ratio 0.56 (0.34 to 0.93, p 0.022) with carboplatin in triple-negative disease, overall survival not significantly improved, no benefit in HER2-positive disease. Homologous recombination deficiency was found in 70.5 percent of 193 triple-negative tumours and predicted pathological complete response (odds ratio 2.60) but not carboplatin benefit; pathological complete response rose from 33.9 to 63.5 percent with carboplatin in HR-deficient tumours and from 20.0 to 29.6 percent in HR-proficient ones."],"nct":"NCT01426880","phase":"2/3","setting":"Early triple-negative and HER2-positive breast cancer: neoadjuvant paclitaxel and non-pegylated liposomal doxorubicin (with bevacizumab in triple-negative and trastuzumab plus lapatinib in HER2-positive disease) with or without carboplatin","sponsor":"German Breast Group (GBG Forschungs GmbH)","result":"Carboplatin increased pathological complete response and improved disease-free survival in triple-negative breast cancer, without benefit in HER2-positive disease.","started":"2011-08","yearReported":2014,"enrolled":595,"enrolledBasis":"registry","outcomes":[{"endpoint":"Pathological complete response (ypT0 ypN0), all patients","primary":true,"unit":"%","arms":[{"name":"Carboplatin added to neoadjuvant therapy","n":295,"value":43.7,"note":"Odds ratio 1.33 (95% CI 0.96 to 1.85)"},{"name":"No carboplatin","n":293,"value":36.9}],"p":"0.107","source":"https://doi.org/10.1016/s1470-2045(14)70160-3"},{"endpoint":"Pathological complete response, triple-negative breast cancer","unit":"%","arms":[{"name":"Carboplatin added to neoadjuvant therapy","n":158,"value":53.2},{"name":"No carboplatin","n":157,"value":36.9}],"p":"0.005","source":"https://doi.org/10.1016/s1470-2045(14)70160-3"},{"endpoint":"Pathological complete response, HER2-positive breast cancer","unit":"%","arms":[{"name":"Carboplatin added to neoadjuvant therapy","n":137,"value":32.8},{"name":"No carboplatin","n":136,"value":36.8}],"p":"0.581","source":"https://doi.org/10.1016/s1470-2045(14)70160-3"},{"endpoint":"Grade 3-4 neutropenia","unit":"%","arms":[{"name":"Carboplatin added to neoadjuvant therapy","n":295,"value":65},{"name":"No carboplatin","n":293,"value":27}],"source":"https://doi.org/10.1016/s1470-2045(14)70160-3"}]},"route":"/trials/geparsixto/","neighbours":{"cancer":[{"id":"tnbc-basal-like-1","kind":"cancer","name":"Basal-like 1 triple-negative breast cancer (BL1)","route":"/cancers/tnbc-basal-like-1/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-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":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"}],"drug":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"lapatinib","kind":"drug","name":"Lapatinib","route":"/drugs/lapatinib/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}],"company":[{"id":"gbg","kind":"company","name":"German Breast Group (GBG)","route":"/companies/gbg/"}],"trial":[{"id":"brightness","kind":"trial","name":"BrighTNess","route":"/trials/brightness/"},{"id":"calgb-40603","kind":"trial","name":"CALGB 40603 (Alliance)","route":"/trials/calgb-40603/"},{"id":"keynote-522","kind":"trial","name":"KEYNOTE-522","route":"/trials/keynote-522/"}],"person":[{"id":"gunter-von-minckwitz","kind":"person","name":"Gunter von Minckwitz","route":"/people/gunter-von-minckwitz/"}],"paper":[{"id":"paper-hahnen-geparsixto-germline-brca-jama-oncol-2017","kind":"paper","name":"Germline mutation status, pathological complete response, and disease-free survival in triple-negative breast cancer: secondary analysis of the GeparSixto randomized clinical trial","route":"/key-papers/paper-hahnen-geparsixto-germline-brca-jama-oncol-2017/"},{"id":"paper-sikov-calgb-40603-carboplatin-bevacizumab-jco-2015","kind":"paper","name":"Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance)","route":"/key-papers/paper-sikov-calgb-40603-carboplatin-bevacizumab-jco-2015/"},{"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/"},{"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","route":"/key-papers/paper-loibl-geparsixto-survival-hrd-ann-oncol-2018/"}],"term":[{"id":"hrd-in-breast-cancer","kind":"term","name":"Homologous recombination deficiency (HRD) in breast cancer","route":"/terms/hrd-in-breast-cancer/"}],"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/"}]}}