Cell type in NSCLC: guiding treatment decisions

This article looked at using cancer cell type to identify patients who may benefit from drugs used to treat EGFR mutations.

Non small-cell lung cancer (NSCLC) is a common type of lung cancer but can be difficult to treat. Some NSCLC’s have mutations (changes to DNA) and these mutations can be targeted by drugs that can successfully treat the cancer. One such mutation is in the epidermal growth factor receptor (EGFR) gene (a gene which codes for a protein important in cancer growth). This mutation may be treated with drugs known as EGFR tyrosine kinase inhibitors (EGFR-TKIs), for example Iressa and Tarceva. However studies have shown that some patients with wild-type (no-mutation) EGFR can also benefit from EGFR-TKI’s. No biomarker (distinguishing feature of disease) currently exists to identify this group of patients.

NSCLC can be made up of different cells; epithelial and mesenchymal are two of the most important. Patients with mesenchymal cancer have been shown to have resistance to EGFR-TKI’s (drug stops working), but patients with epithelial cancer have better response rates to the EGFR-TKI drug or longer progression-free survival (time after treatment during which cancer didn’t worsen). However, in NSCLC cancer cell type can change in a process known as (EMT) epithelial-to-mesenchymal transition, which may result in poorer outcomes.  

202 patients, smokers (41.6%) and non-smokers (59.4%), with average age of 59 and advanced stage IV or recurrent NSCLC (lung cancer that had returned despite treatment) were chosen. 70 patients presented with epithelial cell cancer, 66 with mesenchymal cell cancer. 31 patients had EMT (epithelial cells were changing to mesencymal cells) while the type of cell was not specified in 35 patients.

All patients had undergone chemotherapy and were placed on EGFR-TKI’s gefitinib (Iressa: 29.7%) or erlotinib (Tarceva: 70.3%). Scans were performed 4-6 weeks after beginning therapy, and then every 8 weeks. Metastasis (where cancer spreads beyond the lung) was investigated every 6 months.

Average follow up (13.1 months) showed patients with an EGFR mutation were more likely to have the epithelial cell type. 23.5% of patients with an epithelial cell type showed an objective response (a measurable response such as tumor shrinkage) compared to 11.1% of those with EMT and 2.4% of those with mesenchymal cell type. 

Overall survival was 11.5 months for those with an epithelial cell type compared to 8.9 months for those with EMT and 4.9 months for those with a mesenchymal cell type.

Progression-free survival was 4.4 months for those with an epithelial cell type compared to 1.9 months for those with EMT and 1 for those with a mesenchymal cell type.

The author concluded that patients with an epithelial phenotype had a greater response to the EGFR-TKI therapy than those with a mesenchymal or MET phennotype. This knowledge may be used to predict response to these drugs and guide treatment decisions. 

No biomarker has been identified to exclude patients from recieving EGFR-TKI's, therefore the study is not exposing a new opportunity to this class of patient.