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)

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• 作者：Henry L. Gó ; mez¹ ; Silvia Neciosup¹ ; Cé ; lia Tosello² ; Max Mano³ ; José ; Bines⁴ ; Gustavo Ismael⁵ ; Patrí ; cia X. Santi⁶ ; Hé ; lio Pinczowski⁶ ; Yeni Neró ; n⁷ ; Marcello Fanelli⁸ ; Luis Fein⁹ ; Carlos Sampaio¹⁰ ; Guillermo Lerzo¹¹ ; Adolfo Capó ; ¹² ; Juan J. Zarba¹³ ; Cé ; sar Blajman¹⁴ ; Mirta S. Varela¹⁵ ; Jeovany Martí ; nez-Mesa¹⁶ ; Gustavo Werutsky¹⁶ ; ^{gustavo.werutsky@lacog.org.br" class="auth_mail" title="E-mail the corresponding author} ; Carlos H. Barrios¹⁷
• 关键词：Chemotherapy ; Human epidermal growth factor receptor 2-positive ; Lapatinib ; Metastatic breast cancer ; Treatment outcome
• 刊名：Clinical Breast Cancer
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：16
• 期：1
• 页码：38-44
• 全文大小：547 K

文摘

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/m² on days 1 to 14 (LC), vinorelbine (V), 25 mg/m² on days 1 and 8 (LV), or gemcitabine (G), 1000 mg/m² 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 aminotransferase/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.