# 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)

Source: https://onco.cc/key-papers/paper-sikov-calgb-40603-carboplatin-bevacizumab-jco-2015/  
OnCo record `paper-sikov-calgb-40603-carboplatin-bevacizumab-jco-2015` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The US trial of 443 women that showed adding carboplatin to pre-surgery paclitaxel, doxorubicin and cyclophosphamide raised complete tumour disappearance in breast and nodes from 41 to 54 percent, at the cost of more low blood counts and skipped doses; it and GeparSixto made platinum standard.

## Summary

CALGB 40603 (Alliance), a 2 by 2 factorial open-label randomised phase 2 trial by Sikov, Berry, Perou, Singh and colleagues, gave 443 patients with stage II to III triple-negative breast cancer weekly paclitaxel for 12 weeks then dose-dense doxorubicin and cyclophosphamide, randomised to concurrent carboplatin (area under the curve 6, four cycles) and/or bevacizumab (nine cycles). Patients assigned carboplatin or bevacizumab were less likely to complete chemotherapy without skipped doses, modification or discontinuation; grade 3 or higher neutropenia and thrombocytopenia were more common with carboplatin, and hypertension, infection, thromboembolism, bleeding and postoperative complications with bevacizumab. Carboplatin raised pathological complete response in the breast from 44 to 60 percent (p=0.0018) and in breast and axilla from 41 to 54 percent (p=0.0029); bevacizumab raised breast response (48 to 59 percent, p=0.0089) but not breast and axilla. No more-than-additive interaction was shown.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: tnbc-evidence
- Journal: Journal of Clinical Oncology
- Year: 2015
- DOI: 10.1200/JCO.2014.57.0572
- Authors: Sikov WM, Berry DA, Perou CM, et al.
- Findings: Carboplatin: pathological complete response in breast and axilla 54 vs 41 percent (one-sided p=0.0029); in breast 60 vs 44 percent (p=0.0018).; Bevacizumab raised breast response (59 vs 48 percent) but not breast and axilla response; more toxicity with both agents.
- What it means: With GeparSixto, the trial that put carboplatin into the neoadjuvant triple-negative regimen; KEYNOTE-522's chemotherapy backbone is this one plus pembrolizumab. Bevacizumab, the other arm, left the field.
- Caveats: Phase 2 with a pathological complete response endpoint; survival effects were not powered and the authors said so.; The trial could not identify which patients need platinum, a question still open.

## Sources

- J Clin Oncol 2015: https://doi.org/10.1200/JCO.2014.57.0572
- PubMed: https://pubmed.ncbi.nlm.nih.gov/25092775/
- ClinicalTrials.gov NCT00861705: https://clinicaltrials.gov/study/NCT00861705

## 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: [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Platinum agents](https://onco.cc/technologies/platinum/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/)
- terms: [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/), [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/)
- trials: [GeparSixto](https://onco.cc/trials/geparsixto/), [KEYNOTE-522](https://onco.cc/trials/keynote-522/)
- people: [Charles M. Perou](https://onco.cc/people/charles-perou/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)
- 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/)

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