Do patients with NSCLC and EGFR mutations have a particular pattern of metastasis?

The study investigated whether a common mutation in non small-cell lung cancer (NSCL), an EGFR mutation, can predict metastatic patterns (how cancer spreads to distant parts of the body) in advanced disease.

NSCLC is a common type of lung cancer that can have various underlying causes. Mutations (changes in DNA) are commonly associated with NSCLC, especially in metastatic cancer (cancer has spread to a new part of the body). Two of the most common mutations associated with metastatic NSCLC are in the epidermal growth factor receptor (EGFR) and KRAS proteins.

Patients with both types of mutations are commonly treated with drugs known as tyrosine kinase inhibitors (TKIs), for example Iressa and Tarceva. When compared to patients with both mutated and non-mutated KRAS proteins, those with EGFR mutations are shown to most benefit from treatment with TKI’s.

However a common issue associated with EGFR positive mutations is metastasis into the brain; this is thought to be caused by the fact that TKI’s cannot reach the brain to prevent cancer from occurring. After brain, bone is the next most common site of metastasis for NSCLC, and like brain metastasis it severely impacts the patients’ quality of health and survival.

This study aimed to investigate whether a pattern of metastasis existed in patients with EGFR positive cancer when compared to both patients with and without KRAS mutations.

189 patients were included in the study, 62 patients with EGFR mutations, 65 patients with KRAS mutations and 62 patients with no EGFR/KRAS mutations. 93.5% of all EGFR patients received TKI based therapy at some point during their treatment.

Average overall survival (time between start of treatment and death) was longer in patients with EGFR mutations (26.7 months) compared to those with KRAS mutations (11months) and those with no mutation (11.5months).

Rate of brain metastasis did not differ between the three groups, 32.3% in the EGFR group developed metastasis compared to 35.4% in the KRAS positive group and 40.3% in the non-mutated patients.

No significant difference in metastatic brain cancer survival was observed, however patients with EGFR mutations took longer to develop brain metastasis

Rate of bone metastasis did not differ between the three groups.

Average survival after bone metastasis diagnosis was however shown to be longer in patients with EGFR mutation (15.5months) compared to patients with KRAS mutations (9.0 months) and those with no mutation (3.2 months).

Patients with EGFR mutations were shown to have a better outcome in terms of progression to metastatic disease and survival when associated with bone metastasis.