CBCSG006 试验的生物标志物评估：顺铂加吉西他滨与紫杉醇加吉西他滨作为转移性三阴性乳腺癌一线治疗的随机 III 期试验。
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.
机构信息
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
出版信息
Ann Oncol. 2018 Aug 1;29(8):1741-1747. doi: 10.1093/annonc/mdy209.
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.
背景
CBCSG006 试验报告称顺铂联合吉西他滨（GP）方案作为转移性三阴性乳腺癌（mTNBC）一线治疗的疗效优于紫杉醇联合吉西他滨（GT）方案。本研究重点关注更新的生存数据和疗效潜在生物标志物的探索。
方法
在 55.9%（132/236）的患者中评估了同源重组（HR）面板的种系突变，包括 BRCA1/2。在 48.3%（114/236）的患者中评估了 PD-L1 表达。使用非参数滑动窗口亚组治疗效果模式图（STEPP）方法分析绝对生存获益。所有统计检验均为双侧。
结果
GP 组中位无进展生存期（PFS）为 7.73 个月（95%置信区间[CI]6.46-9.00），GT 组为 6.07 个月（95%CI5.32-6.83）（P=0.005）。未观察到总生存期（OS）的显著差异。HR 状态与治疗对 PFS 的交互作用有显著意义，HR 缺乏状态与 GP 组比 GT 组更高的客观缓解率（ORR）和更长的 PFS 显著相关（71.9%比 38.7%，P=0.008；10.37 比 4.30 个月，P=0.011）。BRCA1/2 种系状态（gBRCA1/2）与治疗对 PFS 的交互作用无显著意义。GP 组中 gBRCA1/2 突变患者的 ORR 更高，PFS 更长（83.3%比 37.5%，P=0.086；8.90 比 3.20 个月，P=0.459）。PD-L1 状态与治疗对 PFS 的交互作用无显著意义，无论 PD-L1 状态如何，两组之间的 ORR、PFS 或 OS 均无显著差异。在 STEPP 分析中，复合风险较低的患者在 PFS 方面的绝对获益大于复合风险较高的患者。
结论
GP 方案作为转移性三阴性乳腺癌患者的一线化疗方案，疗效优于 GT 方案。BRCA1/2 和 HR 面板的种系突变可能是顺铂为基础的治疗方案更好疗效的生物标志物。建立了一个复合风险模型，以指导 TNBC 患者对 GP 治疗的选择。
试验注册
ClinicalTrials.gov，NCT01287624。
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