Can we estimate the benefit of vandetanib and docetaxel in advanced non-small cell lung cancer?

The aim of this study was to determine whether the benefit from combination therapy of vandetanib (Caprelsa) and docetaxel (Taxotere) could be linked to specific biological substances in non-small cell lung cancer (NSCLC) patients.

In advanced stage (IIB/IV) NSCLC, cancer may spread throughout lungs and to other organs of the body. In a previous study, vandetanib was added to docetaxel in a second–line treatment of advanced NSCLC. Second-line treatment is given when first-line/ primary treatment is not adequate. Improvement in duration of survival without progression of disease was observed.

Biomarkers are naturally occurring body substances that are associated with a disease and often used for predicting the progression or outcome of a disease. Evaluating whether certain biomarkers are related to treatment can be an effective way of predicting who will respond best to treatment, or who may need additional treatment. Following the results of the above study, the authors were interested in evaluating if EGFR and KRAS genes (responsible for producing proteins important in signaling within cells) may be potential biomarkers for outcome following this treatment. 

Overall, 1,291 patients were randomly assigned to receive vandetanib plus docetaxel or placebo plus docetaxel. All patients had previously received chemotherapy. Tumor samples from 958 patients were collected for biomarker analysis.

Biomarker analysis revealed there was 49% reduced risk of death in patients receiving vandetanib who had EGFR mutations in the tumors (i.e. EGFR genes in the tumor cells were permanently changed). Patients who had an increased number of EGFR genes in the tumors had similar benefit with vandetanib in overall survival (52% reduced risk of death). No benefit was observed for vandetanib in patients with KRAS mutations in tumors.

The study suggested that NSCLC patients who had increased number of EGFR genes and EGFR mutations in tumors benefitted most from the combination therapy of vandetanib with docetaxel.

If you plan to take the vandetanib –docetaxel combination therapy, you could talk to your doctor about checking EGFR gene status.