A Phase II Randomized Study of Lapatinib Combined With Capecitabine, Vinorelbine, or Gemcitabine in Patients With HER2-Positive Metastatic Breast Cancer With Progression After a Taxane (Latin American Cooperative Oncology Group 0801 Study)

作者：Gomez Henry L; Neciosup Silvia; Tosello Celia; Mano Max; Bines Jose; Ismael Gustavo; Santi Patricia X; Pinczowski Helio; Neron Yeni; Fanelli Marcello; Fein Luis; Sampaio Carlos; Lerzo Guillermo; Capo Adolfo; Zarba Juan J; Blajman Cesar; Varela Mirta S; Martinez Mesa Jeovany; Werutsky Gustavo^*; Barrios Carlos H

来源：Clinical Breast Cancer, 2016, 16(1): 38-44.

DOI：10.1016/j.clbc.2015.10.005

• Chemotherapy
• Human epidermal growth factor receptor 2-positive
• Lapatinib
• Metastatic breast cancer
• Treatment

In LACOG 0801 phase II study 142 patients with HER2+ MBC with progression after taxane were randomized between Lapatinib (L) combined with Capecitabine (C), Vinorelbine (V) or Gemcitabine (G). ORR was 49% in LC, 56% in LV and 41% in LG group. The overall toxicity was manageable in all regimens. Background: Novel targeted agents and combinations have become available in multiple lines of treatment for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). In this context, alternatives to the lapatinib (L) and capecitabine (C) regimen, evaluating L combined with other cytotoxic drugs, are warranted. Patients and Methods: In the present phase II, multicenter study, patients with HER2+ MBC with progression after taxane were randomized between L, 1250 mg, combined with C, 2000 mg/m(2) on days 1 to 14 (LC), vinorelbine (V), 25 mg/m(2) on days 1 and 8 (LV), or gemcitabine (G), 1000 mg/m(2) on days 1 and 8 (LG), every 21 days. The primary endpoint was the overall response rate. Results: A total of 142 patients were included from 2009 to 2012. No differences were found in the patient baseline characteristics. The median age was 51 years, 69% were postmenopausal, 32% had liver metastasis, 57% were hormone receptor negative, and 48% had been previously treated with trastuzumab. The overall response rate was 49% (95% confidence interval [CI], 34.8%-63.4%), 56% (95% CI, 40%-70.4%), and 41% (95% CI, 27%-56.8%) in the LC, LV, and LG groups, respectively. The median progression-free survival was 9 months in the LC arm and 7 months in the other 2 arms (P = .28). The most common grade 3 and 4 adverse events were hand-foot syndrome (18%), diarrhea (6%), and increased alanine anninotransferase/aspartate aminotransferase (4%) in the LC arm; neutropenia (36%), diarrhea (9%), and febrile neutropenia (6%) in the LV arm; and neutropenia (47%), alanine aminotransferase/aspartate aminotransferase (13%), and rash (4%) in the LG arm. Conclusion: LV and LG seem to be active combinations in patients with HER2+ MBC after taxane failure. The overall toxicity was manageable in all regimens.

• 出版日期2016-2
• 单位河北医科大学