乳腺癌患者使用帕妥珠单抗+曲妥珠单抗双靶向+卡培他滨获益吗?

6月 8, 2021 健康社会

美国《临床肿瘤杂志》2017年4月24日在线先发

http://ascopubs.org/doi/abs/10.1200/JCO.2016.70.6267

表皮生长因子受体2阳性的转移性乳腺癌患者在曲妥珠单抗为基础的治疗期间或治疗后出现病情进展后使用曲妥珠单抗加卡培他滨联合或不联合帕妥珠单抗的随机III期试验

目的

在表皮生长因子受体2阳性的转移性乳腺癌患者中,对于已接受过紫杉类药物治疗、且在曲妥珠单抗为基础的治疗期间或治疗后出现病情进展后的患者,评估曲妥珠单抗加卡培他滨联合或不联合帕妥珠单抗的有效性和安全性。

患者和方法

将患者随机分配到A组:曲妥珠单抗8mg/kg→6mg/kg、每3周1次,加卡培他滨1250mg/m2、每日2次(服用2周停1周,每3周重复);或随机分配到B组:帕妥珠单抗840mg→420mg、每3周1次,+与A组同样剂量和用药时间的曲妥珠单抗+与A组同样用药时间的卡培他滨1000mg/m2。主要终点为独立评审机构评估的无进展生存(IRF

PFS)。次要终点包括总生存(OS)和安全性。採用分层检验方法控制对独立评审机构评估的无进展生存、总生存和客观缓解率进行统计检验时的I型错误。

结果

随机分配(意向性治疗)到A组和B组的患者分别为224、228例。在中位随访28.6、25.3个月时的中位IRF

PFS为9.0对比11.1个月(风险比,0.82;95%CI,0.65-1.02;P=0.0731),中期OS为28.1对比36.1个月(风险比,0.68;95%CI,0.51-0.90)。最常见的不良事件(所有级别的不良事件;两组发生率均≥10%,且两组相差≥5%),A组为手足综合征、恶心和中性粒细胞减少,B组是腹泻、皮疹和鼻咽炎。

结论

将帕妥珠单抗加入曲妥珠单抗和卡培他滨方案中没有显着改善IRF PFS,但观察到,帕妥珠单抗能使中位总生存期增加8个月至36.1个月。由于是在主要终点无进展生存期之后进行的总生存期的分层检验,因此不能断言总生存期的统计学意义,但总生存期的差异程度与之前帕妥珠单抗治疗转移性乳腺癌的数据一致。没有发现新的安全性信息。

http://ascopubs.org/doi/abs/10.1200/JCO.2016.70.6267

Randomized Phase III Trial of Trastuzumab Plus Capecitabine With or Without Pertuzumab in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer Who

Experienced Disease Progression During or After Trastuzumab-Based Therapy

Purpose

To assess the efficacy and safety of trastuzumab plus capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer who

experienced disease progression during or after trastuzumab-based therapy and received a prior taxane.

Patients and Methods

Patients were randomly assigned to arm A: trastuzumab 8 mg/kg → 6 mg/kg once every 3 weeks plus capecitabine 1,250 mg/m2 twice a day (2 weeks on, 1 week off, every 3 weeks); or arm B: pertuzumab

840 mg → 420 mg once every 3 weeks plus trastuzumab at the same dose and schedule as arm A plus capecitabine 1,000 mg/m2 on the same schedule as arm A. The primary end point was independent review

facility–assessed progression-free survival (IRF PFS). Secondary end points included overall survival (OS) and safety. Hierarchical testing procedures were used to control type I error for

statistical testing of IRF PFS, OS, and objective response rate.

Results

Randomly assigned (intent-to-treat) populations were 224 and 228 patients in arms A and B, respectively. Median IRF PFS at 28.6 and 25.3 months』 median follow-up was 9.0 v 11.1 months (hazard

ratio, 0.82; 95% CI, 0.65 to 1.02; P = .0731) and interim OS was 28.1 v 36.1 months (hazard ratio, 0.68; 95% CI, 0.51 to 0.90). The most common adverse events (all grades; incidence of ≥ 10% in

either arm and ≥ 5% difference between arms) were hand-foot syndrome, nausea, and neutropenia in arm A, and diarrhea, rash, and nasopharyngitis in arm B.

Conclusion

The addition of pertuzumab to trastuzumab and capecitabine did not significantly improve IRF PFS. An 8-month increase in median OS to 36.1 months with pertuzumab was observed. Statistical

significance for OS cannot be claimed because of the hierarchical testing of OS after the primary PFS end point; however, the magnitude of OS difference is in keeping with prior experience of

pertuzumab in metastatic breast cancer. No new safety signals were identified.

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