Personalized cocktails

Patients with non-small-cell lung cancer (NSCLC) can receive various chemotherapy treatments, but how should their drug regimen be selected? Patients with mutations in their epidermal growth factor receptor (EGFR) respond better to the EGFR inhibitors erlotinib and gefitinib than patients without these mutations, and patients with NSCLC that overexpresses BRCA1 are usually resistant to cisplatin. Rafael Rosell and colleagues conducted a prospective, non-randomized Phase II clinical trial to investigate whether using these biomarkers to determine the therapy patients with NSCLC receive can improve survival rates compared with non-personalized therapy.

Using RNA and DNA isolated from paraffin-embedded tissue from 123 metastatic NSCLC tumours they assessed the status of EGFR and BRCA1. The 12 patients with tumours with EGFR mutations were treated with erlotinib. The 38 patients whose tumours expressed low BRCA1 mRNA levels were treated with cisplatin and gemcitabine. The 40 patients with intermediate BRCA1 levels were treated with docetaxel and cisplatin, and the 33 patients with high levels of BRCA1 were treated with docetaxel. The 2 year survival rate of patients with metastatic NSCLC is 20%, and the authors found that this was improved for the patients with EGFR mutations (73.3% 2 year survival rate after treatment with erlotinib). After 2 years 41.2% of patients expressing low BRCA1 levels were still alive, but 2 year survival rates were low (as expected) for patients with intermediate and high levels of BRCA1 (15.6% and 0%, respectively).

These data indicate that personalized therapy for patients with advanced NSCLC could improve the 2 year survival rate provided accurate biomarkers are used.

Early warning

Shuta Tomida and colleagues have developed a relapse-related signature (RRS-82) for patients with lung adenocarcinoma. Whole genome expression profiles were obtained from 60 patient samples and the signature was constructed according to the 5 year relapse-free survival rates of these patients. The signature, comprising 82 probes, was then validated using several independent data sets.

In an independent set of 27 patients with adenocarcinoma, all stage I patients predicted to have a high risk of relapse experienced relapse and died within the 5 year follow-up period. A further 30 stage I adenocarcinoma samples were also accurately sorted into high risk disease and low risk disease, indicating that RRS-82 is also accurate for patients with early stage disease.

These findings support the hypothesis that patients with poor prognosis can be identified, even with early stage I disease.