2017年12月21日，英国《柳叶刀》肿瘤学分册编辑部在线发表新闻报道：根据最新研究，拉帕替尼加入曲妥珠单抗＋芳香酶抑制剂，显著改善了转移性乳腺癌患者的无进展生存。
该3期研究（ALTERNATIVE）由英国伦敦大学癌症研究院和皇家马斯登医院（世界最早、欧洲最大的肿瘤医院和综合癌症中心）斯蒂芬·庄士敦（不是不是很耳熟？中国清朝末代皇帝溥仪的英国老师就姓庄士敦）教授领导，从29个国家112个机构入组355例曾经接受内分泌治疗＋曲妥珠单抗＋化疗的HER2阳性、激素受体阳性乳腺癌绝经后女性。患者被随机分配接受拉帕替尼＋曲妥珠单抗＋芳香酶抑制剂（120例）或曲妥珠单抗＋芳香酶抑制剂（117例）或拉帕替尼＋芳香酶抑制剂（118例）。该研究主要比较终点为无进展生存。
结果发现：
拉帕替尼＋曲妥珠单抗＋芳香酶抑制剂组、曲妥珠单抗＋芳香酶抑制剂组相比，中位无进展生存显著较长（11个月比5.7个月，风险比：0.62，P=0.0064）。
拉帕替尼＋芳香酶抑制剂组、曲妥珠单抗＋芳香酶抑制剂组相比，中位无进展生存显著较长（8.3个月比5.7个月，风险比：0.71，P=0.0361）。
拉帕替尼＋曲妥珠单抗＋芳香酶抑制剂组与其他两组相比，耐受性较好，停止治疗的患者较少。
庄士敦教授解释道：对于不愿继续接受化疗的HER2阳性激素受体阳性转移性乳腺癌患者，我们正在寻找HER2靶向联合内分泌疗法的最佳形式。HER2双靶向与内分泌治疗一样，对于无进展生存取得了非常可观的结果……接近对这些患者进行化疗时可能看到的水平。
对此，美国哈佛大学医学院达纳法伯癌症研究所的萨拉·托兰尼教授评论称：使用内分泌治疗＋双重抗HER2治疗有效，所以现在仅需回答最佳使用时机的问题。如果患者HER2阳性、激素受体阳性，治疗期间应该采取该策略。但是需要提醒的是，直接对双重HER2阻断与化疗进行比较可能比较困难：将患者随机分组接受化疗与不化疗，意味着毒性反应大不相同。目前，我们可以得出结论：使用抗体（曲妥珠单抗）联合酪氨酸激酶抑制剂（拉帕替尼）进行HER2双靶向治疗＋芳香酶抑制剂，对于该患者人群是最佳的化疗豁免方案。
编者按：本文对于T-DM1、帕妥珠单抗以及其他各种通路抑制剂尚遥不可及的中国而言更有现实意义，尤其人力资源和社会保障部宣布36种药品经谈判成功正式纳入国家基本医疗保险、工伤保险和生育保险药品目录乙类范围后，其中曲妥珠单抗每支由2.58万元降为7600元、拉帕替尼每片由121元降为70元，根据《关于印发〈上海市基本医疗保险、工伤保险和生育保险药品目录（2017年版）〉的通知》和《关于本市试行部分药品集中采购后纳入医疗保险支付的通知》文件规定，个人定额自负标准分别降为3040元、28元。
相关阅读
Lancet Oncol. 2017 Dec 21. [Epub ahead of print]
Improved progression-free survival in metastatic breast cancer.
Talha Khan Burki.
Addition of lapatinib to trastuzumab plus an aromatase inhibitor significantly improves progression-free survival (PFS) in patients with metastatic breast cancer, according to new research.
In the phase 3 ALTERNATIVE trial, Stephen Johnston (Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK) and colleagues enrolled 355 postmenopausal women with HER2-positive, hormone-receptor-positive breast cancer who had previously received endocrine therapy and trastuzumab plus chemotherapy. Patients were randomly assigned to receive lapatinib plus trastuzumab plus an aromatase inhibitor (n=120), trastuzumab plus an aromatase inhibitor (n=117), or lapatinib plus an aromatase inhibitor (n=118).
Median PFS was 11 months (95% CI 8.3-13.8) in the lapatinib-trastuzumab-aromatase inhibitor group versus 5.7 months (5.5-8.4) in the trastuzumab-aromatase inhibitor group (hazard ratio [HR] 0.62 [95% CI 0.45-0.88]; p=0.0064); this comparison was the primary endpoint. Median PFS in the lapatinib-aromatase inhibitor group was 8.3 months (95% CI 5.8-11.2; HR vs the trastuzumab-aromatase inhibitor group 0.71 [95% CI 0.51-0.98]; p=0.0361). Lapatinib-trastuzumab-aromatase was well tolerated and fewer patients discontinued treatment than in the other two groups.
"We were looking for the best form of HER2 targeting in combination with endocrine therapy for HER2-positive, hormone-receptor-positive patients with metastatic breast cancer who were not intending to have chemotherapy", explained Johnston. "The dual targeting of HER2, alongside the endocrine therapy, gave very respectable results in terms of PFS… approaching levels that you might expect to see when you give these patients chemotherapy".
"Using endocrine therapy with dual anti-HER2 therapy works, so it is just a question of when is the best time to utilise it", commented Sara Tolaney (Dana-Farber Cancer Institute, Boston, MA, USA). "At some point in a patient's treatment course they should get this strategy, if they have HER2-positive, hormone receptor-positive disease". But she cautioned that it might be difficult to directly compare dual HER2 blockade with chemotherapy: "Randomising patients between chemotherapy and no chemotherapy implies quite a difference in toxicity. For now, we can conclude HER2 targeting using an antibody and a tyrosine kinase inhibitor plus an aromatase inhibitor is the optimal chemotherapy-sparing regimen for this patient population."
DOI: 10.1016/S1470-2045(17)30952-X
联系客服
