Randomized Trial of Lapatinib Versus Placebo Added to Paclitaxel in the Treatment of Human Epidermal Growth Factor Receptor 2 –Overexpressing Metastatic Breast Cancer
Anatoly Makhson, Beth Newstat, Binghe Xu, Cristina Oliva, George Chen, Henry Gomez, Junian Yang, Mark W. Russo, Michele L. DeSilvio, Wai Lim Leung, Wichit Arpornwirat, Zefei Jiang, Zhenzhou Shen*, Zhongsheng Tong, Zhongzhen Guan, Li Wang, วิชาญ หล่อวิทยา
Internal Medicine Department of Oncology, Sun Yat-Sen Medical University Cancer Center, No. 651 Dongfeng Eastern Rd, Guangzhou, China 510060; e-mail: guanzhzh@mail.sysu.edu.cn
บทคัดย่อ
Purpose: Lapatinib is an oral small-molecule tyrosine kinase inhibitor of both epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2). This study is designed to test whether the addition of lapatinib to paclitaxel improves overall survival (OS) compared with placebo plus paclitaxel in patients with HER2-overexpressing metastatic breast cancer (MBC).
Patients and Methods: This phase III, randomized, double-blind study assessed the efficacy and safety of lapatinib plus paclitaxel compared with placebo plus paclitaxel in patients with newly diagnosed HER2-positive MBC. The primary end point was OS. Secondary end points included progression-free survival (PFS), overall response rate (ORR), clinical benefit rate, and safety.
Results: The addition of lapatinib to paclitaxel significantly improved OS versus paclitaxel (treatment hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.94; P = .0124); median OS was 27.8 versus 20.5 months, respectively. Median PFS was prolonged by 3.2 months, from 6.5 months with placebo plus paclitaxel to 9.7 months with lapatinib plus paclitaxel (HR, 0.52; 95% CI, 0.42 to 0.64; stratified log-rank P < .001). ORR was significantly higher with lapatinib plus paclitaxel compared with placebo plus paclitaxel (69% v 50%, respectively; P < .001). The incidence of grades 3 and 4 diarrhea and neutropenia was higher in the lapatinib plus paclitaxel arm. Only 4% of patients in this group reported febrile neutropenia. Cardiac events were low grade, asymptomatic, and mostly reversible. The incidence of hepatic events was similar in both arms. There were no fatal adverse events in the lapatinib plus paclitaxel arm.
Conclusion: This trial demonstrated that lapatinib combined with paclitaxel offers a significant and clinically meaningful survival advantage over paclitaxel alone in patients with HER2-positive MBC.

ที่มา
Journal of Clinical Oncology ปี 2556, June ปีที่: 31 ฉบับที่ 16 หน้า 1947-1953