# Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response-final results from GeparSixto

Source: https://onco.cc/key-papers/paper-loibl-geparsixto-survival-hrd-ann-oncol-2018/  
OnCo record `paper-loibl-geparsixto-survival-hrd-ann-oncol-2018` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: tnbc-evidence
- Journal: Annals of Oncology
- Year: 2018
- DOI: 10.1093/annonc/mdy460
- Authors: Loibl S, Weber KE, Timms KM, et al.
- 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).
- What it means: 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.

## Sources

- Ann Oncol 2018: https://doi.org/10.1093/annonc/mdy460
- PubMed: https://pubmed.ncbi.nlm.nih.gov/30335131/
- ClinicalTrials.gov NCT01426880: https://clinicaltrials.gov/study/NCT01426880

## Connected records

- key papers: [Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial](https://onco.cc/key-papers/paper-geparsixto-lancet-oncol-2014/)
- cancers: [Early triple-negative breast cancer](https://onco.cc/cancers/tnbc-early/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [HRD & BRCA testing](https://onco.cc/technologies/hrd-testing/), [Platinum agents](https://onco.cc/technologies/platinum/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [myChoice CDx](https://onco.cc/drugs/mychoice-cdx/)
- institutions: [German Breast Group (GBG)](https://onco.cc/institutions/gbg/)
- terms: [Hazard ratio (HR)](https://onco.cc/terms/hazard-ratio/), [Homologous recombination deficiency (HRD)](https://onco.cc/terms/hrd/), [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/)
- trials: [GeparSixto](https://onco.cc/trials/geparsixto/)
- people: [Carsten Denkert](https://onco.cc/people/carsten-denkert/), [Gunter von Minckwitz](https://onco.cc/people/gunter-von-minckwitz/), [Sibylle Loibl](https://onco.cc/people/sibylle-loibl/)
- journals: [Annals of Oncology](https://onco.cc/journals/annals-of-oncology/)
- roadmaps: [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- biomarkers: [HRD-positive (genomic instability score)](https://onco.cc/biomarkers/hrd-positive/), [Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations](https://onco.cc/biomarkers/brca-somatic/)

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