Background
Phase II 2x2 factorial RCT enrolled 454 women with untreated stage II-III triple-negative breast cancer to assess adding carboplatin and/or bevacizumab to neoadjuvant chemotherapy.
Interventions and follow up
Arm A: Weekly paclitaxel x12 then ddAC x4
Arm B: Weekly paclitaxel x12 then ddAC x4 + bevacizumab
Arm C: Weekly paclitaxel x12 + carboplatin AUC6 q3wk x4 then ddAC x4
Arm D: Weekly paclitaxel x12 + carboplatin then ddAC x4 + bevacizumab
Primary endpoint: Pathologic complete response (pCR) in breast (ypT0/is) and breast/axilla (ypT0/isN0)
Arm B: Weekly paclitaxel x12 then ddAC x4 + bevacizumab
Arm C: Weekly paclitaxel x12 + carboplatin AUC6 q3wk x4 then ddAC x4
Arm D: Weekly paclitaxel x12 + carboplatin then ddAC x4 + bevacizumab
Primary endpoint: Pathologic complete response (pCR) in breast (ypT0/is) and breast/axilla (ypT0/isN0)
Results
pCR breast (with vs without carboplatin): 60% vs 46%; OR 1.76, P=.0018
pCR breast (with vs without bevacizumab): 59% vs 48%; OR 1.58, P=.0089
pCR breast (carboplatin + bevacizumab): 67%
pCR breast/axilla (with vs without carboplatin): 54% vs 41%; OR 1.71, P=.0029
pCR breast/axilla (with vs without bevacizumab): 52% vs 44%; OR 1.36, P=.057
pCR breast/axilla (carboplatin + bevacizumab): 60%
pCR breast (with vs without bevacizumab): 59% vs 48%; OR 1.58, P=.0089
pCR breast (carboplatin + bevacizumab): 67%
pCR breast/axilla (with vs without carboplatin): 54% vs 41%; OR 1.71, P=.0029
pCR breast/axilla (with vs without bevacizumab): 52% vs 44%; OR 1.36, P=.057
pCR breast/axilla (carboplatin + bevacizumab): 60%
Adverse events
Hematologic: More grade 3-4 neutropenia and thrombocytopenia with carboplatin.
Cardiovascular: Hypertension with bevacizumab.
Surgical/wound: Increased surgical and wound-healing complications with bevacizumab.
Cardiovascular: Hypertension with bevacizumab.
Surgical/wound: Increased surgical and wound-healing complications with bevacizumab.
Conclusions
Adding carboplatin to neoadjuvant chemotherapy significantly raises pCR in TNBC; bevacizumab also increases pCR but with added toxicity and no clear long-term role.
Abbreviations:
wP: paclitaxel 80 mg/m2 weekly x12
Bev: bevacizumab 10 mg/kg q2wk x9
ddAC: dose-dense doxorubicin/cyclophosphamide x4
Carbo: carboplatin AUC6 q3wk x4
Abbreviations:
wP: paclitaxel 80 mg/m2 weekly x12
Bev: bevacizumab 10 mg/kg q2wk x9
ddAC: dose-dense doxorubicin/cyclophosphamide x4
Carbo: carboplatin AUC6 q3wk x4
Key Limitations
Phase II, powered for pCR rather than survival; no statistically significant long-term EFS/OS benefit from carboplatin on later analysis. Bevacizumab added toxicity without durable benefit. Predates immunotherapy-containing regimens.
Clinical Context
With GeparSixto, supported incorporating carboplatin into neoadjuvant TNBC regimens (ASCO/ESMO), informing platinum use in BRCA-associated and higher-risk TNBC. Largely superseded for stage II-III TNBC by the pembrolizumab-containing KEYNOTE-522 backbone.
References