Taroh Satoh, Kinki University School of Medicine, Osaka; Toshihiko Doi and Atsushi Ohtsu, National Cancer Center Hospital East, Chiba; Akihito Tsuji, Kochi Health Sciences Center, Kochi; Yasushi Omuro, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital; Akihira Mukaiyama and Mikiro Kobayashi, GlaxoSmithKline, Tokyo; Hiroto Miwa, Hyogo College of Medicine, Hyogo, Japan; Rui-Hua Xu, Sun Yat-Sen University Cancer Center, Guangzhou; Guo-Ping Sun, First Affiliated Hospital of Anhui Medical University, Hefei; Jian-Ming Xu, 307 Hospital of the People's Liberation Army; Jin-Wan Wang, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Beijing; Jin Li, Fudan University Cancer Hospital, Shanghai; Shu-Kui Qin, People's Liberation Army 81 Hospital; Ji-Feng Feng, Cancer Hospital of Jiangsu Province, Nanjing, People's Republic of China; Hyun Cheol Chung, Yonsei Cancer Center, Yonsei University College of Medicine; Yung-Jue Bang, Seoul National University College of Medicine, Seoul; Ik-Joo Chung, Chonnam National University Hwasun Hospital, Jeollanamdo, South Korea; and Kun-Huei Yeh, National Taiwan University Hospital, Taipei, Taiwan.
J Clin Oncol. 2014 Jul 1;32(19):2039-49. doi: 10.1200/JCO.2013.53.6136. Epub 2014 May 27.
In Asian countries, paclitaxel once per week is used as second-line treatment in advanced gastric cancer, including human epidermal growth factor receptor 2 (HER2) -positive tumors. The role of anti-HER2 agents, including lapatinib, in this setting and population is unclear.
TyTAN was a two-part, parallel-group, phase III study in Asian patients. An open-label, dose-optimization phase (n = 12) was followed by a randomized phase (n = 261), in which patients who were HER2 positive by fluorescence in situ hybridization (FISH) received lapatinib 1,500 mg once per day plus once-per-week paclitaxel 80 mg/m(2) or paclitaxel alone. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), time to progression (TTP), overall response rate (ORR), time to response, response duration, and safety. Analyses were based on immunohistochemistry (IHC) and gastrectomy status, prior trastuzumab therapy, and regional subpopulations.
Median OS was 11.0 months with lapatinib plus paclitaxel versus 8.9 months with paclitaxel alone (P = .1044), with no significant difference in median PFS (5.4 v 4.4 months) or TTP (5.5 v 4.4 months). ORR was higher with lapatinib plus paclitaxel versus paclitaxel alone (odds ratio, 3.85; P < .001). Better efficacy with lapatinib plus paclitaxel was demonstrated in IHC3+ compared with IHC0/1+ and 2+ patients and in Chinese compared with Japanese patients. A similar proportion of patients experienced adverse events with each treatment (lapatinib plus paclitaxel, 100% v paclitaxel alone, 98%).
Lapatinib plus paclitaxel demonstrated activity in the second-line treatment of patients with HER2 FISH-positive IHC3+ advanced gastric cancer but did not significantly improve OS in the intent-to-treat population.
在亚洲国家，紫杉醇每周一次被用作晚期胃癌（包括人表皮生长因子受体 2 [HER2]阳性肿瘤）的二线治疗药物。曲妥珠单抗联合紫杉醇已在 HER2 阳性晚期胃癌的一线治疗中显示出良好的抗肿瘤活性和生存获益，然而，在亚洲国家，曲妥珠单抗联合紫杉醇一线治疗晚期胃癌的适应证尚未获批。在这种情况下和人群中，使用包括拉帕替尼在内的抗 HER2 药物的作用尚不清楚。
TyTAN 是一项在亚洲患者中进行的两部分、平行组、III 期研究。在开放标签、剂量优化阶段（n = 12）之后，进行了随机阶段（n = 261），其中通过荧光原位杂交（FISH）检测为 HER2 阳性的患者接受拉帕替尼 1500 mg 每日一次联合每周紫杉醇 80 mg/m2，或单独接受紫杉醇治疗。主要终点是总生存期（OS）。次要终点包括无进展生存期（PFS）、疾病进展时间（TTP）、总缓解率（ORR）、缓解时间、缓解持续时间和安全性。分析基于免疫组织化学（IHC）和胃切除术状态、曲妥珠单抗治疗史以及区域亚人群。
拉帕替尼联合紫杉醇组的中位 OS 为 11.0 个月，而紫杉醇单药组为 8.9 个月（P =.1044），中位 PFS（5.4 个月比 4.4 个月）和 TTP（5.5 个月比 4.4 个月）无显著差异。拉帕替尼联合紫杉醇组的 ORR 高于紫杉醇单药组（比值比，3.85；P <.001）。与 IHC0/1+和 2+患者相比，拉帕替尼联合紫杉醇组在 IHC3+患者中显示出更好的疗效，与日本患者相比，中国患者显示出更好的疗效。两种治疗方法的不良反应发生率相似（拉帕替尼联合紫杉醇组 100%，紫杉醇单药组 98%）。
拉帕替尼联合紫杉醇在治疗 HER2 FISH 阳性 IHC3+晚期胃癌患者的二线治疗中显示出活性，但在意向治疗人群中并未显著改善 OS。
