Henry L Gómez1, Silvia Neciosup1, Célia Tosello2, Max Mano3, José Bines4, Gustavo Ismael5, Patrícia X Santi6, Hélio Pinczowski6, Yeni Nerón7, Marcello Fanelli8, Luis Fein9, Carlos Sampaio10, Guillermo Lerzo11, Adolfo Capó12, Juan J Zarba13, César Blajman14, Mirta S Varela15, Jeovany Martínez-Mesa16, Gustavo Werutsky17, Carlos H Barrios18. 1. Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru. 2. Instituto Brasileiro de Controle do Câncer, São Paulo, São Paulo, Brazil. 3. Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo, São Paulo, Brazil. 4. Instituto Nacional de Câncer, Rio de Janeiro, Brazil. 5. Fundação Doutor Amaral Carvalho, Jaú, Brazil. 6. Instituto de Ensino e Pesquisa São Lucas, Santo André, Brazil. 7. Centro de Pesquisas Oncológicas de Santa Catarina, Florianópolis, Brazil. 8. Hospital A.C. Camargo, São Paulo, Brazil. 9. Centro Oncológico de Rosário, Rosário, Argentina. 10. Clínica Amo, Salvador, Brazil. 11. Investigaciones Clínicas Ciudad de Buenos Aires, Buenos Aires, Argentina. 12. Fundación Centro Oncológico de Integración Regional, Mendoza, Argentina. 13. Centro San Roque, Tucumán, Argentina. 14. ISIS Clínica Especializada, Santa Fé, Argentina. 15. CER Instituto Médico, Buenos Aires, Argentina. 16. Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil. 17. Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil. Electronic address: gustavo.werutsky@lacog.org.br. 18. Pontifical Catholic University of Rio Grande do Sul School of Medicine, Hospital São Lucas, Porto Alegre, Brazil.
Abstract
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 aftertaxane 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 withtrastuzumab. 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.
RCT Entities:
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 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.