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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.
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.
Carboplatin 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.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
595 enrolled.
Odds ratio 1.33 (95% CI 0.96 to 1.85)
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Pathological complete response (ypT0 ypN0), all patientsprimary | Carboplatin added to neoadjuvant therapy | 295 | 43.7% | - | 0.107 | link |
| No carboplatin | 293 | 36.9% | ||||
| Pathological complete response, triple-negative breast cancer | Carboplatin added to neoadjuvant therapy | 158 | 53.2% | - | 0.005 | link |
| No carboplatin | 157 | 36.9% | ||||
| Pathological complete response, HER2-positive breast cancer | Carboplatin added to neoadjuvant therapy | 137 | 32.8% | - | 0.581 | link |
| No carboplatin | 136 | 36.8% | ||||
| Grade 3-4 neutropenia | Carboplatin added to neoadjuvant therapy | 295 | 65% | - | - | link |
| No carboplatin | 293 | 27% |
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.
Germline status changes the reading of the platinum question: in early TNBC the carboplatin benefit was seen in non-carriers, so a BRCA result argues for testing everyone rather than reserving platinum for carriers.
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.
This is the paper Europe PMC returns for registry id NCT01426880 with the most citations, so it is the natural first reading for anyone following the GeparSixto trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
Shares Trastuzumab, Paclitaxel / nab-paclitaxel, Breast cancer (all types) and the tag subtype-trials.
Shares Paclitaxel / nab-paclitaxel, Carboplatin, Cytotoxic chemotherapy and the tag subtype-trials.
Shares Platinum agents, Carboplatin, Cytotoxic chemotherapy and the tag subtype-trials.
Shares Lapatinib, Breast cancer (all types) and the tag subtype-trials.
Shares Lapatinib, Trastuzumab and the tag subtype-trials.
Shares Doxorubicin, Cytotoxic chemotherapy and the tag subtype-trials.
Shares Platinum agents, Cytotoxic chemotherapy and the tag subtype-trials.
Shares Trastuzumab, Breast cancer (all types) and the tag subtype-trials.