282MO - Abraxane plus cisplatin compared with gemcitabine plus cisplatin as first-line treatment in patients with metastatic triple-negative breast cancer (GAP): A multicenter, randomized, open-label, phase III trial

Background

Cisplatin showed great clinical benefit in metastatic triple-negative breast cancer (mTNBC) and has been included as first-line treatment when combined with gemcitabine in Chinese as well as German AGO guidelines. However, an optimal partner with cisplatin remains to be exploited. As nanoparticle albumin-bound (nab)-paclitaxel gained a high response in the treatment of mTNBC, we conducted GAP trial to assess the efficacy and safety of nab-paclitaxel plus cisplatin (AP) versus GP as first-line therapy for patients with mTNBC.

Methods

In this phase III trial, we randomly assigned (in a 1:1 ratio) patients with untreated metastatic triple-negative breast cancer to receive AP (nab-paclitaxel 125mg/m² on day 1, 8 and cisplatin 75 mg/m² on day 1) or GP (gemcitabine 1250 mg/m² on days 1, 8 and cisplatin 75 mg/m² on day 1) intravenously every 3 weeks until progression disease, intolerable toxicity or withdrawal of consent. The primary endpoint was progression-free survival (PFS) and secondary end points included overall response rate (ORR), overall survival (OS) and safety.

Results

127 patients received AP and 126 received GP from 9 centers (median follow-up, 17.8 months for AP group and 14.9 months for GP group). The median PFS was 9.9 months with AP, as compared with 7.5 months with GP (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.50-0.87; P=0.004). The ORR was significantly higher with AP (81.1%, vs. 56.3% with GP; P<0.001). A trend for improved OS in the AP group was observed (median, not reached; HR, 0.75; 95% CI, 0.51-1.11; P=0.16). Of the grade 3 or 4 adverse events, there was a significantly higher incidence of neuropathy (18.8% vs. 0%) in the AP group, and thrombocytopenia (3.9% vs. 29.4 %) in the GP group. Serious adverse events occurred in 3.9% patients (5/127) in the AP group and 2.4% patients (3/126) of patients in the GP group.

Conclusions

Nab-paclitaxel plus cisplatin improved PFS and ORR in patients with metastatic triple-negative breast cancer as a first-line treatment, as compared with GP, while OS results are much awaited. Safety profiles of the two combinations were different but the adverse events were manageable.

Clinical trial identification

NCT02546934.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Fudan University Shanghai Cancer Center.

Disclosure

All authors have declared no conflicts of interest.