曲妥珠单抗-美坦新偶联物联合帕妥珠单抗与紫杉类药物联合曲妥珠单抗联合帕妥珠单抗用于人表皮生长因子受体 2 阳性高危早期乳腺癌：III 期 KAITLIN 研究。

Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study.

机构信息

Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.

Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

出版信息

J Clin Oncol. 2022 Feb 10;40(5):438-448. doi: 10.1200/JCO.21.00896. Epub 2021 Dec 10.

PURPOSE

We aimed to improve efficacy and reduce toxicity of high-risk human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC) treatment by replacing taxanes and trastuzumab with trastuzumab emtansine (T-DM1).

METHODS

The phase III KAITLIN study (NCT01966471) included adults with excised HER2-positive EBC (node-positive or node-negative, hormone receptor-negative, and tumor > 2.0 cm). Postsurgery, patients were randomly assigned 1:1 to anthracycline-based chemotherapy (three-four cycles) and then 18 cycles of T-DM1 plus pertuzumab (AC-KP) or taxane (three-four cycles) plus trastuzumab plus pertuzumab (AC-THP). Adjuvant radiotherapy/endocrine therapy was permitted. Coprimary end points were invasive disease-free survival (IDFS) in the intention-to-treat node-positive and overall populations with hierarchical testing.

RESULTS

The median follow-up was 57.1 months (interquartile range, 52.1-60.1 months) for AC-THP (n = 918) and 57.0 months (interquartile range, 52.1-59.8 months) for AC-KP (n = 928). There was no significant IDFS difference between arms in the node-positive (n = 1,658; stratified hazard ratio [HR], 0.97; 95% CI, 0.71 to 1.32) or overall population (n = 1846; stratified HR, 0.98; 95% CI, 0.72 to 1.32). In the overall population, the three-year IDFS was 94.2% (95% CI, 92.7 to 95.8) for AC-THP and 93.1% (95% CI, 91.4 to 94.7) for AC-KP. Treatment completion rates (ie, 18 cycles) were 88.4% for AC-THP and 65.0% for AC-KP (difference driven by T-DM1 discontinuation because of laboratory abnormalities [12.5%]). Similar rates of grade ≥ 3 (55.4% 51.8%) and serious adverse events (23.3% 21.4%) occurred with AC-THP and AC-KP, respectively. KP decreased clinically meaningful deterioration in global health status versus THP (stratified HR, 0.71; 95% CI, 0.62 to 0.80).

CONCLUSION

The primary end point was not met. Both arms achieved favorable IDFS. Trastuzumab plus pertuzumab plus chemotherapy remains the standard of care for high-risk HER2-positive EBC.

目的

通过用曲妥珠单抗-美坦新偶联物（T-DM1）替代紫杉烷和曲妥珠单抗，来提高高危人表皮生长因子受体 2（HER2）阳性早期乳腺癌（EBC）治疗的疗效并降低毒性。

方法

III 期 KAITLIN 研究（NCT01966471）纳入了切除的 HER2 阳性 EBC（淋巴结阳性或淋巴结阴性、激素受体阴性和肿瘤＞2.0cm）的成年患者。手术后，患者随机以 1:1 分配至接受基于蒽环类药物的化疗（3-4 个周期），然后接受 T-DM1 联合帕妥珠单抗（AC-KP）或紫杉烷（3-4 个周期）联合曲妥珠单抗联合帕妥珠单抗（AC-THP）治疗 18 个周期。允许接受辅助放疗/内分泌治疗。主要共同终点是意向治疗的淋巴结阳性和总体人群的无侵袭性疾病生存（IDFS），采用分层检验。

结果

AC-THP（n=918）和 AC-KP（n=928）的中位随访时间分别为淋巴结阳性（n=1658；分层危险比[HR]，0.97；95%CI，0.71 至 1.32）或总体人群（n=1846；分层 HR，0.98；95%CI，0.72 至 1.32）的无病生存（DFS）无显著差异。在总体人群中，AC-THP 的 3 年 IDFS 为 94.2%（95%CI，92.7 至 95.8），AC-KP 的 3 年 IDFS 为 93.1%（95%CI，91.4 至 94.7）。AC-THP 的治疗完成率（即 18 个周期）为 88.4%，AC-KP 的治疗完成率为 65.0%（差异归因于因实验室异常而停用 T-DM1[12.5%]）。AC-THP 和 AC-KP 分别发生 55.4%（51.8%）和 23.3%（21.4%）的≥3 级（55.4% 51.8%）和严重不良事件（23.3% 21.4%）的发生率相似。与 THP 相比，KP 使全球健康状况的临床显著恶化率降低（分层 HR，0.71；95%CI，0.62 至 0.80）。