Yongsheng Wang

Utidelone plus capecitabine versus capecitabine alone for heavily pretreated metastatic breast cancer refractory to anthracyclines and taxanes: a multicentre, open-label, superiority, phase 3, randomised controlled trial

BACKGROUND Utidelone, a genetically engineered epothilone analogue, has shown promise as a potential treatment for breast cancer in phase 1 and 2 trials. The aim of this phase 3 trial was to compare the efficacy and safety of utidelone plus capecitabine versus capecitabine alone in patients with metastatic breast cancer. METHODS We did a multicentre, open-label, superiority, phase 3, randomised controlled trial in 26 hospitals in China. Eligible participants were female patients with metastatic breast cancer refractory to anthracycline and taxane chemotherapy regimens. We randomly assigned participants (2:1) using computer based randomisation and block sizes of 6 to a 21-day cycle of either utidelone (30 mg/m2 intravenously once per day on days 1-5) plus capecitabine (1000 mg/m2 orally twice per day on days 1-14), or capecitabine alone (1250 mg/m2 orally twice per day on days 1-14), until disease progression or unacceptable toxicity occurred. Patients, physicians, and assessors were not masked to treatment allocation; however, an independent radiology review committee used to additionally assess response was masked to allocation. The primary endpoint was centrally assessed (by an independent radiology review committee) progression-free survival, and analysed using the Kaplan-Meier product-limit method in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of study drug. Follow-up is ongoing. This study is registered at ClinicalTrials.gov, number NCT02253459. FINDINGS Between Aug 8, 2014, and Dec 14, 2015, we enrolled and randomly assigned 270 patients to treatment with utidelone plus capecitabine, and 135 to capecitabine alone. Median follow-up for progression-free survival was 6·77 months (IQR 3·81-10·32) for the utidelone plus capecitabine group and 4·55 months (2·55-9·39) for the capecitabine alone group. Median progression-free survival by central review in the utidelone plus capecitabine group was 8·44 months (95% CI 7·95-9·92) compared with 4·27 months (3·22-5·68) in the capecitabine alone group; hazard ratio 0·46, 95% CI 0·36-0·59; p<0·0001. Peripheral neuropathy was the most common grade 3 adverse event in the utidelone plus capecitabine group (58 [22%] of 267 patients vs 1 [<1%] of 130 patients in the capecitabine alone group). Palmar-plantar erythrodysaesthesia was the most prominent grade 3 adverse event in the capacitabine alone group (in 10 [8%] of 130 patients) and was the next most frequent grade 3 event in the utidelone plus capecitabine group (in 18 [7%] of 267 patients). 16 serious adverse events were reported in the combination therapy group (diarrhoea was the most common, in three [1%] patients) and 14 serious adverse events were reported in the monotherapy group (the most common were diarrhoea, increased blood bilirubin, and anaemia, in two [2%] patients for each event). 155 patients died (99 in the combination therapy arm, 56 in the monotherapy arm). All deaths were related to disease progression except for one in each group (attributed to pericardial effusion in the combination therapy group and dyspnoea in the monotherapy group) that were considered possibly or probably treatment-related. INTERPRETATION Despite disease progression with previous chemotherapies, utidelone plus capecitabine was more efficacious compared with capecitabine alone for the outcome of progression-free survival, with mild toxicity except for peripheral sensory neuropathy, which was manageable. The findings from this study support the use of utidelone plus capecitabine as an effective option for patients with metastatic breast cancer. FUNDING Beijing Biostar Technologies, Beijing, China.

Disparities of Trastuzumab Use in Resource‐Limited or Resource‐Abundant Regions and Its Survival Benefit on HER2 Positive Breast Cancer: A Real‐World Study from China

BACKGROUND Trastuzumab is a key component of therapy for human epidermal growth receptor 2 (HER2) positive breast cancer. Because real-world data are lacking, the present research was conducted to evaluate the actual use of and the effectiveness of trastuzumab in the real world in China. METHODS Inpatients with HER2 positive invasive breast cancer from 13 hospitals in Eastern China (2010-2015, n = 1,139) were included in this study. We aimed to assess the actual use of trastuzumab and to evaluate potential efficacy from trastuzumab in real-world research. RESULTS Of 1,017 patients with early stage breast cancer (EBC), 40.5% (412/1,017) received trastuzumab therapy. Patients with EBC in resource-abundant regions (gross domestic product per capita >

National consensus in China on diagnosis and treatment of patients with advanced breast cancer

15,000 and trastuzumab included in Medicare) are more likely to receive trastuzumab than those in resource-limited regions (37.3% vs. 13.0%, p < .05). After metastasis, 50.8% (366/720) patients received trastuzumab as their first-line therapy. More than 10% of patients with metastatic breast cancer (MBC) continued trastuzumab therapy after twice progression in resource-abundant regions, whereas more than 40% of patients never received any trastuzumab therapy during the whole course of therapy in resource-limited regions. Overall, the improvement in survival for trastuzumab versus non-trastuzumab was substantial in EBC (hazard ratio [HR] = 0.609, 95% confidence interval [CI]: 0.505-0.744) and in MBC (HR = 0.541, 95% CI: 0.418-0.606). This association was greater for patients with MBC who had never received trastuzumab (HR = 0.493, 95% CI: 0.372-0.576) than for those who had received adequate trastuzumab therapy in EBC stage (HR = 0.878, 95% CI: 0.506-1.431). CONCLUSION This study showed great disparities in trastuzumab use in different regions and different treatment stages. Both EBC and MBC patients can benefit from trastuzumab, as the survival data show; however, when trastuzumab is adequate in the early stage, a further trastuzumab-based therapy in first-line treatment of MBC will be ineffective, especially for those with short disease-free survival, and a second line of anti-HER2 therapy will be recommended. (Research number: CSCO-BC RWS 15001). IMPLICATIONS FOR PRACTICE This article explores the disparities in the rates of trastuzumab use due to the inequitable allocation of medical resources in China. The irrational use can be found both in resource-abundant regions and in resource-limited regions. Although trastuzumab-based therapy improved survival, the actual use of trastuzumab in the early stage of breast cancer may influence the subsequent therapeutic effect after metastasis. These findings from real-world research could help to optimize HER2 therapy after metastasis, especially in regions with limited access to these expensive targeted drugs.

Interpreting Advanced Breast Cancer Consensus Guidelines for Use in China

The recently available guidelines on the management of advanced breast cancer (ABC) organized by Chinese Anti-Cancer Association, Committee of Breast Cancer Society (CACA-CBCS) do not elucidate ABC in details. To instruct clinicians in treatment of ABC, a Chinese expert consensus meeting on diagnosis and treatment of ABC was held in June 2014 and a consensus is developed. The following consensus provides the level of evidence and supporting documents for each recommendation, and introduces research topics to be urgently addressed. Notably, the consensus on diagnosis and treatment of ABC in China is developed to be applied nationwide. In different areas, multidisciplinary treatment (MDT) tailored to the each patient and the disease itself should be applied based on the basic principles of modern oncology.

Efficacy and safety analysis of trastuzumab and paclitaxel based regimen plus carboplatin or epirubicin as neoadjuvant therapy for clinical stage II-III, HER2-positive breast cancer patients: a phase 2, open-label, multicenter, randomized trial

Abstract 58Background:In 2011, an international panel of breast cancer experts developed the first Advanced Breast Cancer (ABC) Consensus Guidelines to provide standards and improved care for the multidisciplinary care of patients with this common disease. We sought to adapt the ABC guidelines for China, incorporating cultural standards and available Chinese resource, and identifying suitable formed guideline.Methods:We organized the Chinese Consensus Guidelines Conference for ABC (CABC) yearly from 2013 through 2015 in Beijing as a joint effort between the China Medical Womens Association, the Organization of Beijing Sunshine Great Wall Oncology Program, Peking University, The panel included 50 breast oncology and surgery experts from 20 provinces, as well as two external consultant oncologists from the U.S. and Singapore. Permission was obtained from the ABC Chair to use the guidelines as a basis for our discussion. All questions were presented and discussed in detail, including a review of current app...