Gemcitabine or Abraxane Combined with cisPlatin (GAP) as First-Line Treatment in Patients with Metastatic Triple-Negative Breast Cancer: A Multicenter, Randomized, Open-Label, Phase 3 Trial

Abstract

Background: Platinum is recommended in combination with gemcitabine in the treatment of metastatic triple-negative breast cancer (mTNBC), such as carboplatin plus gemcitabine and cisplatin plus gemcitabine. However, an optimal partner with cisplatin remains to be established. Herein, Gemcitabine or Abraxane (nab-paclitaxel) combined with cisPlatin (GAP) was administered to assess the efficacy and safety of AP versus GP as first-line therapy for patients with mTNBC.

Methods: In this phase 3, randomized, open-label trial, patients from nine institutions or hospitals in China with histologically confirmed mTNBC, an ECOG performance status of 0–1 and at least one measurable lesion received first-line therapy of AP (nab-paclitaxel 125 mg/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 using an interactive web response system with the stratification factors of visceral metastasis and number of metastatic sites. The primary endpoint was progression-free survival (PFS) assessed in the intention-to-treat population. The safety profile was assessed in patients who received at least one dose of the treatment.

Results: Between Mar 30, 2016, and Oct 09, 2019, 254 patients were randomly assigned to treatment (127 to receive AP and 127 to receive GP). After a median follow-up of 16.3 months, the median PFS was 9.9 months (95% confidence interval [CI] 8.99-10.88) with AP as compared to 7.5 months (6.66-8.40) with GP (hazard ratio [HR], 0.66; 95% CI, 0.50-0.87; P=0.004). A significant higher objective response rate (ORR) (81.1% vs. 55.9%) and a trend for improved overall survival (OS) (median 26.3 vs. 22.9 months) were achieved with AP. Of the grade 3 or 4 adverse events, a significantly higher incidence of neuropathy (24 [18.9%] vs. 0 [0%]) occurred in the AP group, while thrombocytopenia was noted (5[3.9%] vs. 37 [29.4%]) in the GP group. There were no treatment-related deaths.

Conclusions: AP significantly improved PFS and ORR in patients with mTNBC as first-line treatment as compared to GP with no unexpected toxicity. Besides its cost-efficiency and application for all comers, the highest ORR and the longest PFS and OS based on our knowledge warrant further assessment of adding novel agents to the nab-paclitaxel/platinum backbone.

Trial Registration: The trial is registered with ClinicalTrials.gov, number NCT02546934.

Funding: National Natural Science Foundation of China.

Declaration of Interests: The authors declare no competing interests.

Ethics Approval Statement: The trial protocol was approved by Celgene Global Medical in 2015. All patients provided written informed consent, and the study was approved by the institutional review board at each participating center. The study was conducted in accordance with the Declaration of Helsinki

Keywords: metastatic triple-negative breast cancer, Chemotherapy, cisplatin, nab-paclitaxel