ABSTRACT
Purpose@#The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC). @*Materials and Methods@#An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate. @*Results@#Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC. @*Conclusion@#Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.
ABSTRACT
The incidence of pancreatic cancer has been obviously increasing in China over the last decade, however, those patients with advanced pancreatic cancer are suffering from limited treatment strategies and poor clinical prognosis. Chemotherapy improved the overall survival of cases with advanced pancreatic cancer to 8-11 months, and erlotinib brought an additional survival of only 10 days. In this article, the recent progresses on advanced pancreatic cancer were reviewed at the genetic and molecular sub-typing levels, and corresponding clinical transformation studies summarized, some of which have showed encouraging clinical prospects but others have failed due to the complexity of pancreatic cancer. By learning from experiences in the successful therapeutic strategies and lessons from the failed cases, we hope to optimize future clinical research from bedside to bench.