Randomized trial of lapatinib versus placebo added to paclitaxel in the treatment
of human epidermal growth factor receptor 2-overexpressing metastatic breast
cancer.
Author(s): Guan Z(1), Xu B, DeSilvio ML, Shen Z, Arpornwirat W, Tong Z, Lorvidhaya V, Jiang
Z, Yang J, Makhson A, Leung WL, Russo MW, Newstat B, Wang L, Chen G, Oliva C,
Gomez H.
Affiliation(s): Author information:
(1)Sun Yat-Sen University Cancer Center, Guangzhou, China. guanzhzh@mail.sysu.edu.cn
Publication date & source: 2013, J Clin Oncol. , 31(16):1947-53
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.
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