随机、开放标签、III 期临床试验：伊立替康联合卡培他滨对比卡培他滨单药治疗既往接受蒽环类和紫杉类药物治疗的转移性乳腺癌患者：PROCEED 试验（KCSG BR 11-01）。

Randomized Open Label Phase III Trial of Irinotecan Plus Capecitabine versus Capecitabine Monotherapy in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane: PROCEED Trial (KCSG BR 11-01).

机构信息

Division of Internal Medicine, Center for Breast Cancer, National Cancer Center, Goyang, Korea.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

出版信息

Cancer Res Treat. 2019 Jan;51(1):43-52. doi: 10.4143/crt.2017.562. Epub 2018 Feb 14.

PURPOSE

We investigated whether irinotecan plus capecitabine improved progression-free survival (PFS) compared with capecitabine alone in patients with human epidermal growth factor 2 (HER2) negative and anthracycline and taxane pretreated metastatic breast cancer (MBC).

MATERIALS AND METHODS

A total of 221 patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250 mg/m2 twice a day, days 1-14) every 3 weeks. The primary endpoint was PFS.

RESULTS

There was no significant difference in PFS between the combination and monotherapy arm (median, 6.4 months vs. 4.7 months; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63 to 1.11; p=0.84). In patients with triple-negative breast cancer (TNBC, n=90), the combination significantly improved PFS (median, 4.7 months vs. 2.5 months; HR, 0.58; 95% CI, 0.37 to 0.91; p=0.02). Objective response rate was numerically higher in the combination arm, though it failed to reach statistical significance (44.4% vs. 33.3%, p=0.30). Overall survival did not differ between arms (median, 20.4 months vs. 24.0 months; p=0.63). While grade 3 or 4 neutropenia was more common in the combination arm (39.6% vs 9.0%), hand-foot syndrome was more often observed in capecitabine arm. Quality of life measurements in global health status was similar. However, patients in the combination arm showed significantly worse symptom scales especially in nausea/vomiting and diarrhea.

CONCLUSION

Irinotecan plus capecitabine did not prove clinically superior to single-agent capecitabine in anthracycline- and taxane-pretreated HER2 negative MBC patients. Toxicity profiles of the two groups differed but were manageable. The role of added irinotecan in patients with TNBC remains to be elucidated.

目的

我们研究了在人表皮生长因子 2（HER2）阴性和蒽环类和紫杉烷预处理的转移性乳腺癌（MBC）患者中，伊立替康联合卡培他滨是否比卡培他滨单药治疗能改善无进展生存期（PFS）。

材料和方法

共 221 例患者被随机分配至伊立替康（80mg/m2，第 1 和 8 天）和卡培他滨（1000mg/m2，每日 2 次，第 1-14 天）组或卡培他滨单药组（1250mg/m2，每日 2 次，第 1-14 天）。主要终点是 PFS。

结果

联合组和单药组的 PFS 无显著差异（中位数分别为 6.4 个月和 4.7 个月；风险比[HR]，0.84；95%置信区间[CI]，0.63 至 1.11；p=0.84）。在三阴性乳腺癌（TNBC，n=90）患者中，联合治疗显著改善了 PFS（中位数分别为 4.7 个月和 2.5 个月；HR，0.58；95%CI，0.37 至 0.91；p=0.02）。联合组的客观缓解率虽略高，但未达到统计学意义（44.4% vs. 33.3%，p=0.30）。两组的总生存期无差异（中位数分别为 20.4 个月和 24.0 个月；p=0.63）。联合组的 3 级或 4 级中性粒细胞减少症更常见（39.6% vs. 9.0%），而卡培他滨组更常见手足综合征。全球健康状况的生活质量测量相似。然而，联合组的患者在恶心/呕吐和腹泻等症状评分方面明显更差。