Mutation predictive of patient survival in advanced non-small-cell lung cancer

This study investigated the ability of mutations in the protein TP53 to predict outcome  of patients with advanced NSCLC.

Non small-cell lung cancer (NSCLC) is a common type of lung cancer that is both difficult to treat and has a poor survival rate. A common cause associated with developing NSCLC is a mutation (changes to DNA) in the TP53 protein. Known as a tumor suppressor protein, TP53 is meant to prevent cancer in a healthy person.

However over 32.5% of advanced-stage NSCLC patients have a mutation in the protein making it a common factor in the development of advanced NSCLC. TP53 mutations are divided into two groups, disruptive (protein does not work) and non-disruptive (protein still has some ability to work). 

This study investigated the ability of a mutation type to predict outcome of patients with advanced NSCLC.

318 patients were included in this study. Patients were divided into two study groups depending on the state of their epidermal growth factor receptor (EGFR) gene (a gene which is commonly mutated and produces a protein important in cancer growth).125 patients were placed in the non-mutated EGFR group and 193 patients were placed in the mutated group.

All patients with non-mutated EGFR received treatment with platinum-based chemotherapy, for example cisplatin (Platinol), carboplatin (Paraplatin) or oxaliplatin (Eloxatin). 146 patients with EGFR-mutations received Tarceva (Erlotinib) and the remaining 47 received chemotherapy. Average follow-up was 14.36 months.

No significant difference was found to exist between the rates of TP53 mutations found in  the two EGFR study groups; 34.4% in patients with non-mutated EGFR and 25.9% in those with mutated EGFR. Current and past smokers were however shown to be at increased risk of TP53 mutation.

Progression-free survival (interval between the start of therapy and disease progression or death) was 7.0 months in patients with non-disruptive TP53 mutations versus 8.3 months for the remaining patients.

Overall survival (time between start of treatment and death) was longer in patients with EGFR-mutations (26.5 months) when compared to the non-mutated group (12.8 months). Overall survival of patients with non-disruptive TP53 mutations was shorter (13.3 months) than those with disruptive mutations (24.6 months).

When EGFR status was factored in it was shown that patients with non-disruptive mutations had a shorter overall survival. Patients with non-disruptive TP53 mutations and non-mutated EGFR overall survival was 8.5 months compared to an average of 15.6 months for all other patients. Patients with non-disruptive TP53 mutations and mutated-EGFR had an overall survival of 17.8 months compared to an average of 28.4 months to the remaining patients.

Patients with non-disruptive mutations in their TP53 were shown to have shorter progression-free survival and overall survival regardless of EGFR status.