CISPLATIN FOR TNBC

Lancet Oncol. 2015 Mar 17. pii: S1470-2045(15)70064-1. doi: 10.1016/S1470-2045(15)70064-1. [Epub ahead of print]

Cisplatin plus gemcitabine versus paclitaxel plus gemcitabine as first-line therapy for metastatic triple-negative breast cancer (CBCSG006): a randomised, open-label, multicentre, phase 3 trial.

Hu XC1, Zhang J2, Xu BH3, Cai L4, Ragaz J5, Wang ZH2, Wang BY2, Teng YE6, Tong ZS7, Pan YY8, Yin YM9, Wu CP10, Jiang ZF11, Wang XJ12, Lou GY13, Liu DG14, Feng JF15, Luo JF16, Sun K17, Gu YJ18, Wu J19, Shao ZM19.

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Abstract

BACKGROUND: 

Platinum chemotherapy has a role in the treatment of metastatic triple-negative breast cancer but its full potential has probably not yet been reached. We assessed whether a cisplatin plus gemcitabine regimen was non-inferior to or superior to paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer.

METHODS: 

For this open-label, randomised, phase 3, hybrid-designed trial undertaken at 12 institutions or hospitals in China, we included Chinese patients aged 18-70 years with previously untreated, histologically confirmed metastatic triple-negative breast cancer, and an ECOG performance status of 0-1. These patients were randomly assigned (1:1) to receive either cisplatin plus gemcitabine (cisplatin 75 mg/m2 on day 1 and gemcitabine 1250 mg/m2 on days 1 and 8) or paclitaxel plus gemcitabine (paclitaxel 175 mg/m2 on day 1 and gemcitabine 1250 mg/m2 on days 1 and 8) given intravenously every 3 weeks for a maximum of eight cycles. Randomisation was done centrally via an interactive web response system using block randomisation with a size of eight, with no stratification factors. Patients and investigator were aware of group assignments. The primary endpoint was progression-free survival and analyses were based on all patients who received at least one dose of assigned treatment. The margin used to establish non-inferiority was 1·2. If non-inferiority of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine was achieved, we would then test for superiority. The trial is registered with ClinicalTrials.gov, number NCT01287624.

FINDINGS: 

From Jan 14, 2011, to Nov 14, 2013, 240 patients were assessed for eligibility and randomly assigned to treatment (120 in the cisplatin plus gemcitabine group and 120 in the paclitaxel plus gemcitabine group). 236 patients received at least one dose of assigned chemotherapy and were included in the modified intention-to-treat analysis (118 per group). After a median follow-up of 16·3 months (IQR 14·4-26·8) in the cisplatin plus gemcitabine group and 15·9 months (10·7-25·4) in the paclitaxel plus gemcitabine group, the hazard ratio for progression-free survival was 0·692 (95% CI 0·523-0·915; pnon-inferiority<0 p="" span="" style="bottom: -0.25em; font-size: 0.8461em; line-height: 1.6363em; position: relative; top: 0.25em; vertical-align: baseline;">superiority

=0·009, thus cisplatin plus gemcitabine was both non-inferior to and superior to paclitaxel plus gemcitabine. Median progression-free survival was 7·73 months (95% CI 6·16-9·30) in the cisplatin plus gemcitabine group and 6·47 months (5·76-7·18) in the paclitaxel plus gemcitabine group. Grade 3 or 4 adverse events that differed significantly between the two groups included nausea (eight [7%] vs one [<1 1-4="" 10="" 11="" 42="" 60="" abstracttext="" addition="" adverse="" alopecia="" anaemia="" anaphylaxis="" and="" anorexia="" bone="" but="" cardiogenic="" cisplatin="" compared="" constipation="" deaths.="" drug-related="" events="" fewer="" five="" for="" four="" fracture="" gemcitabine="" grade="" group="" groups="" had="" haemorrhage="" hypokalaemia="" hypomagnesaemia="" in="" interstitial="" more="" musculoskeletal="" neuropathy="" neutropenia="" no="" none="" of="" one="" paclitaxel="" pain="" pathological="" patients="" peripheral="" plus="" pneumonia="" respectively.="" seen="" serious="" severe="" significantly="" six="" subcutaneous="" syncope="" ten="" the="" there="" three="" thrombocytopenia="" treatment-related="" two="" vomiting="" vs="" were="" with="">

INTERPRETATION: 

Cisplatin plus gemcitabine could be an alternative or even the preferred first-line chemotherapy strategy for patients with metastatic triple-negative breast cancer.