HER2 IHC was established in the ToGA trail. Additional HER2 gene amplification was found in 13% and 27% in IHC þ1 and þ2 tumours, Lenalidomide respectively, although almost all gastric tumours with IHC þ3 HER2 expression showed gene amplification. In a post hoc analysis, we performed FISH for gene amplification in þ3 HER2 expressing tumours in order to explain the conflicting data regarding HER2 amplification in IHC þ2 HER2 tumours and the poor treatment results found in this study. In accordance with Safran et al this study shows no consistent HER2 gene amplification in IHC þ3 expressing pancreatic adenocarcinoma as seen in other cancers, suggesting some other pathways resulting in protein overexpression. Contrary to breast, colon, biliary and gastric cancer in pancreatic cancer IHC þ2 HER2 expression and especially þ3 HER2 expression does not correlate with gene amplification.
May be HER2 overexpression in pancreatic cancer is due to gene deregulation rather than gene amplification as postulated by Ukita et al for intrahepatic biliary tract cancer. Nelarabine Arranon Due to the low incidence of IHC þ3 HER2 expression, only 17 patients could be treated Raltegravir Integrase inhibitor with trastuzumab and capecitabine in this trial. Although the therapy was well tolerated, and PFS and OS are comparable to previous regimens, the combination of trastuzumab and capecitabine did not perform favourably compared with historical standard gemcitabine or capecitabine chemotherapy. The RR reported by Safran et al was 24% overall and even 34% for patients with HER2 gene amplification resulting in a median OS of 7.5 months.
These encouraging results led to our study design and numbers calculated. Gemcitabine is considered as the chemotherapy of choice for metastatic pancreatic cancer. There is no comparative trial cox2 inhibitor between Gemcitabine and Capecitabine, but Capecitabine has to be considered to have superior response rates over bolus 5 FU and similar to Gemcitabine. Therefore, we designed this study in intention for a patient friendly protocol including an oral chemotherapy. In addition there was the hope that combination therapy including capecitabine might result in better response rates taking into account the disappointing results using gemcitabine in combination with anti growth factor therapies. Median PFS in our trial was 65 days with an OS of 6.9 month, which is similar to single agent capecitabine.
In a recent study, published in abstract form capecitabine in combination with lapatinib, a small molecule, tyrosine kinase inhibitor of epidermal growth factor receptor and HER2 showed language disappointing antitumour activity with an OS of 4 months. Our study showed an median OS of 6.9 months, but taken together capecitabine in combination with anti HER2 therapy does not seem to significantly improve treatment results in comparison with historical capecitabine monotherapy. Therefore, a comparative trial can not be recommended. That one third of IHC 3þ HER2 positive tumours showed no HER2 amplification found in a post hoc analysis might be one explanation for the disappointing treatment results adding anti HER2 treatment to capecitabine. The phenomenon that targeted therapy containing regimens are ineffective in pancreatic cancer while the same regimens have shown significant activity in other GI tumour entities.