Biomarker assessment of the CBCSG006 trial: a randomized phase III trial of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer.

Background: CBCSG006 trial reported the superior efficacy of cisplatin plus gemcitabine (GP) regimen than paclitaxel plus gemcitabine (GT) regimen as first-line treatment of metastatic triple-negative breast cancer (mTNBC). This study focused on the updated survival data and the explorations of potential biomarkers for efficacy. Patients and methods: Germ-line mutations of homologous recombination (HR) panel, BRCA1/2 included, were evaluated in 55.9% (132/236) patients. PD-L1 expression was evaluated in 48.3% (114/236) patients. A nonparametric sliding-window subpopulation treatment effect pattern plot (STEPP) methodology was used to analyze the absolute survival benefits. All statistical tests were two-sided. Results: Median progression-free survival (PFS) was 7.73 [95% confidence interval (CI) 6.46-9.00] months for GP arm and 6.07 (95% CI 5.32-6.83) months for GT arm (P = 0.005). No significant difference in overall survival (OS) was observed. There was significant interaction between HR status and treatment for PFS and status of HR deficient significantly correlated with higher objective response rate (ORR) and longer PFS in GP arm than in GT arm (71.9% versus 38.7%, P = 0.008; 10.37 versus 4.30 months, P = 0.011). There was no significant interaction between germ-line BRCA1/2 (gBRCA1/2) status and treatment for PFS. Patients with gBRCA1/2 mutation had numerically higher ORR and prolonged PFS in GP arm than in GT arm (83.3% versus 37.5%, P = 0.086; 8.90 versus 3.20 months, P = 0.459). There was no significant interaction between PD-L1 status and treatment for PFS, and no significant differences in ORR, PFS or OS between two arms regardless of PD-L1 status. In STEPP analysis, patients with lower composite risks had more absolute benefits in PFS than those with higher composite risks. Conclusions: GP regimen has superior efficacy than GT regimen as first-line chemotherapy for mTNBC patients. Germ-line mutations of BRCA1/2 and HR panel are possible biomarkers for better performance of cisplatin-based regimens. A composite risk model was developed to guide patient selection for GP treatment in TNBC patients. Trial registration: ClinicalTrials.gov, NCT01287624.

[Cost-effectiveness of multiple screening modalities on breast cancer in Chinese women from Shanghai].

Objective: To determine the most cost-effective modality for breast cancer screening in women living in Shanghai. Methods: A Markov model for breast cancer was redeveloped based on true effect which was derived from a project for detection of women at high risk of breast cancer and an organized breast cancer screening program conducted simultaneously in Minhang district, Shanghai, during 2008 to 2012. Parameters of the model were derived from literatures. General principles related to cost-effectiveness analysis were used to compare the costs and effects of 12 different screening modalities in a simulated cohort involving 100 000 women aged 45 years. Incremental cost-effectiveness ratio (ICER) was used to determine the most cost-effective modality. Sensitivity analysis was conducted to evaluate how these factors affected the estimated cost-effectiveness. Results: The modality of biennial CBE followed by ultrasonic and mammography among those with positive CBE was observed as the most cost-effective one. The costs appeared as 182 526 Yuan RMB per life year gained and 144 386 Yuan RMB per quality adjusted life-year (QALY) saved, which were within the threshold of 2-3 times of local per capita Gross Domestic Product. Results from sensitivity analysis showed that, due to higher incidence rate of breast cancer in Shanghai, the cost per QALY would be 64 836 Yuan RMB lower in Shanghai than the average level in China. Conclusion: Our research findings showed that the biennial CBE program followed by ultrasonic and mammography for those with positive CBE results might serve as the optimal breast cancer screening modality for Chinese women living in Shanghai, and thus be widely promoted in this population elsewhere.