IHC/FISH discrepancies were attributed to basolateral membranous immunoreactivity of glandular cells resulting in incomplete membranous reactivity and/or a higher rate of tumour heterogeneity in gastric cancer compared with breast cancer. With modifications to the IHC scoring system, the HercepTest is considered valid for the identification of HER2+ gastric tumours for this clinical trial. Correlation of HER2 scores with clinical outcomes will be needed to determine which patients might benefit from trastuzumab therapy.

Trastuzumab in combination with capecitabine or 5-fluorouracil and cisplatin is approved by the European Medicines Agency for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive (immunohistochemistry 3+ or immunohistochemistry 2+/fluorescence in situ hybridization-positive or immunohistochemistry 2+/silver in situ hybridization-positive) metastatic adenocarcinoma of the stomach or gastro-esophageal junction. Approvals are underway in other countries, with recent approvals granted in the United States and Japan. Experience and data from trastuzumab use in breast cancer have highlighted the importance of quality HER2 testing and scoring to ensure accurate identification of patients eligible for treatment. HER2 testing in gastric cancer differs from testing in breast cancer due to inherent differences in tumor biology; gastric cancer more frequently shows HER2 heterogeneity (focal staining) and incomplete membrane staining. Consequently, gastric cancer-specific HER2 testing protocols have been developed and standardized and it is imperative that these recommendations be adhered to. Given the predictive value of HER2 protein levels with response in the trastuzumab for GAstric cancer study (ToGA), immunohistochemistry should be the initial testing methodology and fluorescence in situ hybridization or silver in situ hybridization should be used to retest immunohistochemistry 2+ samples. Wherever possible, bright-field methodologies should be used as these are considered to be superior to fluorescent methodologies at identifying heterogeneous staining. Specific training is required before embarking on HER2 testing in gastric cancer, irrespective of the experience of HER2 testing in breast cancer. This paper provides the most up-to-date practical guidance on HER2 testing and scoring in patients with gastric and gastro-esophageal junction cancer, as agreed by a panel of expert pathologists with extensive experience of HER2 testing particularly reflecting the European Medicines Agency-approved indication. It is anticipated that these recommendations should ensure accurate and consistent HER2 testing, which will allow appropriate selection of patients eligible for treatment with trastuzumab.

HER2 determination by IHC and FISH correlates with clinical response data in the WO16229 trial with high concordance of IHC and FISH results. Polysomy is the major cause of response in FISH-negative cases; polysomic cases should be retested by strictly standardised IHC.

NCT 00567554, www.clinicaltrials.gov.

Background State-of-the art therapy for recurrent ovarian cancer (ROC) suitable for platinum-based re-treatment includes bevacizumab-containing combinations (eg, carboplatin/paclitaxel, carboplatin/gemcitabine) or the most active non-bevacizumab regimen: carboplatin/pegylated liposomal doxorubicin (PLD). This head-to-head trial compared a standard bevacizumab-containing regimen versus carboplatin/PLD combined with bevacizumab. Methods In this multicentre, open-label, randomised, phase 3 trial, eligible patients had histologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with first disease recurrence >6 months after first-line platinum-based chemotherapy, and were aged ≥18 years with Eastern Cooperative Oncology Group performance status 0-2. Patients were stratified by platinum-free interval, residual tumour, prior anti-angiogenic therapy, and study group language, and centrally randomised 1:1 using randomly permuted blocks of size two, four, or six to six intravenous cycles of carboplatin (AUC 4, day 1) plus gemcitabine (1000 mg/m 2 , days 1 and 8) every 3 weeks or six cycles of carboplatin (AUC 5, day 1) plus PLD (30 mg/m 2 , day 1) every 4 weeks, both given with bevacizumab (15 mg/kg every 3 weeks or 10 mg/kg every 2 weeks) until disease progression or toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS). Efficacy data were analysed in the intention-to-treat population (all randomised patients). Safety was analysed in all patients who received at least one dose of study drug. This completed study is registered with ClinicalTrials.gov number NCT01837251.