Sebastian Mondaca1, Matthew Margolis1, Francisco Sanchez-Vega2,3, Philip Jonsson2,4, Jamie C Riches1, Geoffrey Y Ku1, Jaclyn F Hechtman3, Yaelle Tuvy1, Michael F Berger2,3,5, Manish A Shah1, David P Kelsen1, David H Ilson1, Kenneth Yu1, Zoe Goldberg1, Andrew S Epstein1, Avni Desai1, Vincent Chung6, Joanne F Chou4, Marinela Capanu4, David B Solit1,2,3, Nikolaus Schultz2,3, Yelena Y Janjigian7. 1. Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, 300 E. 66th Street, Room 1033, New York, NY, 10065, USA. 2. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. 3. Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. 4. Department of Epidemiology-Biostatistics, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. 5. Physiology, Biophysics and Systems Biology Program, Weill Cornell Medical College, New York, NY, USA. 6. Department of Medical Oncology and Therapeutics Research, City of Hope Cancer Center, Duarte, CA, USA. 7. Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, 300 E. 66th Street, Room 1033, New York, NY, 10065, USA. janjigiy@mskcc.org.
Abstract
BACKGROUND: Trastuzumab with cisplatin and fluoropyrimidine is the standard treatment in metastatic HER2-positive gastric or gastroesophageal (GE) junction adenocarcinoma; however, there is limited data on the efficacy of trastuzumab in combination with a three-drug regimen in this setting. We examined the efficacy and safety of modified docetaxel, cisplatin and 5 fluorouracil (mDCF) plus trastuzumab in a single-arm multicenter phase II trial. METHODS: Previously untreated patients with HER2-positive metastatic gastric or GE junction adenocarcinoma were treated with mDCF and trastuzumab every 2 weeks. The primary endpoint was 6-month progression-free survival (PFS); secondary endpoints included objective response rate, overall survival (OS), and toxicity. RESULTS: We enrolled 26 patients with metastatic HER2-positive gastric or GE junction adenocarcinoma between February 2011 and June 2015. The median age of patients was 62 years; 96% had a Karnofsky performance status equal to or greater than 80%. With a median follow-up of 25.4 months, the 6-month PFS was 73% (95% CI 51-86%). The objective response rate was 65%, the median PFS was 13 months (95% CI 6.4-20.7) and the median OS was 24.9 months (95% CI 14.4-42.5). Grade 3/4 toxicities included neutropenia (42%), fatigue (23%), and hypophosphatemia (15%). There were no episodes of febrile neutropenia. CONCLUSION: The combination of mDCF and trastuzumab is effective and safe in patients with metastatic HER2-positive gastric or GE junction adenocarcinoma and can be considered as an option for selected patients. This trial is registered at ClinicalTrials.gov, number NCT00515411.
BACKGROUND:Trastuzumab with cisplatin and fluoropyrimidine is the standard treatment in metastatic HER2-positive gastric or gastroesophageal (GE) junction adenocarcinoma; however, there is limited data on the efficacy of trastuzumab in combination with a three-drug regimen in this setting. We examined the efficacy and safety of modified docetaxel, cisplatin and 5 fluorouracil (mDCF) plus trastuzumab in a single-arm multicenter phase II trial. METHODS: Previously untreated patients with HER2-positive metastatic gastric or GE junction adenocarcinoma were treated with mDCF and trastuzumab every 2 weeks. The primary endpoint was 6-month progression-free survival (PFS); secondary endpoints included objective response rate, overall survival (OS), and toxicity. RESULTS: We enrolled 26 patients with metastatic HER2-positive gastric or GE junction adenocarcinoma between February 2011 and June 2015. The median age of patients was 62 years; 96% had a Karnofsky performance status equal to or greater than 80%. With a median follow-up of 25.4 months, the 6-month PFS was 73% (95% CI 51-86%). The objective response rate was 65%, the median PFS was 13 months (95% CI 6.4-20.7) and the median OS was 24.9 months (95% CI 14.4-42.5). Grade 3/4 toxicities included neutropenia (42%), fatigue (23%), and hypophosphatemia (15%). There were no episodes of febrile neutropenia. CONCLUSION: The combination of mDCF and trastuzumab is effective and safe in patients with metastatic HER2-positive gastric or GE junction adenocarcinoma and can be considered as an option for selected patients. This trial is registered at ClinicalTrials.gov, number NCT00515411.
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