Blood protein levels could predict benefit of gefitinib in patients with advanced disease

This study investigated using levels of the proteins MUC1 and VEGF to predict the benefit of gefitinib in patients with advanced NSCLC.

Non small-cell lung cancer (NSCLC) is a common type of lung cancer that can be difficult to treat. 65-75% of cases are presented at an advanced stage. Chemotherapy is often the initial therapy used, however NSCLC has a poor 5-year survival rate (65%) due to reccurrence (cancer returns) and metastasis (cancer spreads).

Drugs to target mutations (changes to DNA) in proteins associated with NSCLC exist. One such mutation is in the epidermal growth factor receptor (EGFR) gene (a gene which produces a protein important in cancer growth). This mutation may be treated with drugs known as EGFR tyrosine kinase inhibitors (EGFR-TKIs), for example Iressa (gefitinib) and Tarceva (Erlotinib). Studies have also shown the certain patients with wild type (non-mutated) EGFR can also benefit from EGFR-TKIs.

Identifying any NSCLC patients who may benefit from EGFR-TKI therapy can be difficult as many tumours are inoperable (not suitable for surgical removal) and therefore samples of the tumor cannot be removed for testing. Biomarkers (distinguishing features of disease, usually proteins) in the blood are one method being investigated to predict response to EGFR-TKIs.

Measuring the levels of the proteins MUC1 (mucin 1 or KL-6) and VEGF (vascular endothelial growth factor) in the blood is suggested to be linked to response to chemotherapy, progression-free survival and overall survival.

The study measured the levels of MUC1 and VEGF in patients treated with gefitinib to investigate how they were related to response and patient survival.

66 patients (43.9% female) were selected for the study. A control of 55 patients with benign lung disease (lung disease not associated with serious illness) was used. 33.3% of tumors were diagnosed with EGFR mutations. All patients had progressive disease despite previous chemotherapy.

All patients received gefitinib (250mg daily). MUC1 and VEGF levels were measured at the beginning of therapy and 4 weeks after therapy. Low levels of MUC1 levels were determined as 4.2 or below. Low levels of VEGF were determined as 3.3 or below. The blood levels of both proteins were significantly higher in NSCLC patients compared to benign lung disease patients both before and after treatment. Levels of both decreased with treatment. 

Both before and after treatment, levels of both biomarkers were significantly lower in patients who achieved a partial response (some disappearance of signs and symptoms of cancer) or stable disease (no worsening of the cancer) compared to those whose disease progressed. 

Average follow up was 11.2 months. For the whole group, the average progression-free survival (time without disease progression) was 5.2 months and overall survival was 10.8 months. Higher levels of both biomarkers were associated with reduced progression-free and overall survival. 

The study concluded that both MUC1 and VEGF are markers that may predict response to gefitinib, progression-free and overall survival. 

Only a small number of patients were tested; to properly evaluate the benefit of using MUC1 and VEGF as biomarkers to predict response to gefitinib or other EGFR-TKIs a larger study will be required.