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.

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/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1 and 8) or paclitaxel plus gemcitabine (paclitaxel 175 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) 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<0·0001, psuperiority=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%]), vomiting (13 [11%] vs one [<1%]), musculoskeletal pain (none vs ten [8%]), anaemia (39 [33%] vs six [5%]), and thrombocytopenia (38 [32%] vs three [3%]), for the cisplatin plus gemcitabine compared with the paclitaxel plus gemcitabine groups, respectively. In addition, patients in the cisplatin plus gemcitabine group had significantly fewer events of grade 1-4 alopecia (12 [10%] vs 42 [36%]) and peripheral neuropathy (27 [23%] vs 60 [51%]), but more grade 1-4 anorexia (33 [28%] vs 10 [8%]), constipation (29 [25%] vs 11 [9%]), hypomagnesaemia (27 [23%] vs five [4%]), and hypokalaemia (10 [8%] vs two [2%]). Serious drug-related adverse events were seen in three patients in the paclitaxel plus gemcitabine group (interstitial pneumonia, anaphylaxis, and severe neutropenia) and four in the cisplatin plus gemcitabine group (pathological bone fracture, thrombocytopenia with subcutaneous haemorrhage, severe anaemia, and cardiogenic syncope). There were no treatment-related deaths. INTERPRETATION: Cisplatin plus gemcitabine could be an alternative or even the preferred first-line chemotherapy strategy for patients with metastatic triple-negative breast cancer. FUNDING: Shanghai Natural Science Foundation.

The importance of biopsy in clinically diagnosed metastatic lesions in patients with breast cancer.

BACKGROUND: Receptor status discordance, such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status between primary breast cancer and metastatic lesions has been reported. The aim of this study was to evaluate the biopsy of clinically diagnosed metastatic lesions and to determine the changes in hormonal receptor and HER2 status of the metastatic lesions. METHODS: Sixty-three patients with clinically diagnosed metastatic breast cancer underwent an excisional biopsy or core needle aspiration guided by computed tomography/ultrasound. ER, PR and HER2 were assessed by immunohistochemistry (IHC). RESULTS: A total of 48 metastases (76.2%) and nine second primary malignancies (14.3%, seven primary lung cancers and two primary pancreatic cancers) were found. The discrepancies between ER, PR and HER2 status between the primary breast cancer and metastatic lesions were 14.6%, 16.7% and 8.3%, respectively. Six lesions (9.5%) were proved benign upon biopsy. CONCLUSIONS: The biopsy of clinically suspicious metastatic lesions could histologically confirm the diagnosis of metastasis, evaluate discrepancies between ER, PR and HER2 status and exclude secondary malignancy, which might change the therapeutic strategy for breast cancer patients.

[Use of rebiopsy for clinically diagnosed metastatic lesion in patients with breast cancer].

OBJECTIVE: To evaluate the roles of rebiopsy for clinically diagnosed metastatic lesion in detecting the changes of hormonal receptors and second malignancy. METHODS: The metastatic lesions were rebiopsied by core needle aspiration or incision in 42 patients with a clinical diagnosis of metastatic breast cancer by computed tomography or ultrasound. RESULTS: None of major complications occurred. Thirty-one metastases were proved pathologically. The discrepancies between primary breast cancer and metastatic lesions of estrogen receptor(ER), progesterone receptor(PR), HER-2 statuses were 22.6%, 25.8% and 9.7% respectively. And 7 second malignancies were found (16.7%, 5 primary lung and 2 primary pancreas cancers). Four patients showed no relapse through rebiopsy. CONCLUSION: The rebiopsy of clinically diagnosed metastatic breast cancer may find the discrepancies of ER, PR, HER-2 statuses and second malignancy so as to change the therapeutic strategies of patients.

[In vitro chemo-sensitivity MTT assay guided intraperitoneal chemotherapy for malignant ascites].

OBJECTIVE: To evaluate the feasibility and efficacy of intraperitoneal chemotherapy for malignant ascites caused by different types of abdominal cancers guided by chemo-sensitivity methyl tetrojolium coloremetric (MTT) assay in vitro. METHODS: Cancer cells in the malignant ascites were collected for MTT assay to determine the chemo-sensitivity. The drug producing the highest or the second highest inhibition rate was selected for intraperitoneal chemotherapy. The correlation between the results of MTT assay and the response of malignant ascites, the clinical features, Karnofsky performance score (KPS) and prognosis were analyzed. RESULTS: MTT assay indicated that Taxotere (TXT) and Hydroxycamptothecin (HCPT) were the most effective to cancer cells in malignant ascites, and HCPT was mostly frequently used for intraperitoneal chemotherapy (56.9%). Twenty-four patients showed response by intraperitoneal chemotherapy (complete response: 7; partial response: 17) with a slightly significant correlation between the results of MTT assay and response of malignant ascites (P = 0. 014). The KPS of the responders was improved significantly (P < 0.001), and the response of malignant ascites to intraperitoneal chemotherapy was demostrated as an independent prognostic factor by multi-variate analysis in this series. CONCLUSION: In vitro chemo-sensitivity MTT assay guided intraperitoneal chemotherapy for malignant ascites is simple, effective and safe, which can improve the KPS and prognosis of the responders.