Local therapies with continued EGFR tyrosine kinase inhibitors (erlotinib or gefitinib) for resistant non-small cell lung cancer

This study examined the benefits of local therapies for patients with EGFR mutant non-small cell lung cancer (NSCLC) that has progressed despite tyrosine kinase inhibitor (TKI) treatment.

Non-small-cell lung cancer (NSCLC) cells may contain different genetic mutations that cause these cells to divide and spread rapidly, promoting tumor formation. A mutation in the epidermal growth factor receptor (EGFR) gene is responsible for one form of NSCLC in which cells over produce the EGFR protein. Patients with EGFR-positive NSCLC respond to treatment with a class of drugs known as tyrosine kinase inhibitors (TKIs). TKIs, such as erlotinib (Tarceva) or gefitinib (Iressa), inhibit the stimulating action of the EGFR protein on cellular growth. Despite the success of these agents, patients eventually relapse due to the development of drug resistance (when the cancer cells find a way to bypass the effect of the drug).

Progression free survival (PFS; the amount of time between treatment and until the disease worsens or progresses) for TKI treatment in NSCLC is usually 12–16 months. Once TKI resistance has occurred, the average survival of advanced NSCLC patients is several months. No additional EGFR targeted therapies are available, and treatment options are limited to either chemotherapy (with or without TKI continuation) or participation in a clinical trial.

Local therapies, such as radiation treatments to the area of progression, radiofrequency ablation (using a probe guided to the tumor that heats and destroys cancer cells), and metastasectomy (removing the new tumors by surgery) are common treatment strategies in other cancers, but are rarely used in NSCLC that has progressed despite treatment.

This study examined whether EGFR-positive NSCLC patients, that have progressed after TKI resistance, could benefit from local therapies.

The researchers managed to identify 18 patients that received one or more local therapies for advanced EGFR-positive NSCLC after TKI resistance and progression. The most common local treatment received was a metastasectomy to remove pulmonary metastases (spread of the tumor within the lung). Most patients (15 out of the 18) resumed erlotinib or gefitinib treatment after the local therapy.

After receiving local therapy, the time to progression of the disease was 10 months. Overall, the average survival time after local therapy was 41 months.

This study showed that local therapy, followed by continued treatment with erlotinib or gefitinib, may lead to longer progression free intervals and a better overall survival than that seen with standard treatment options. Further studies to investigate the clinical benefit of local therapies are warranted.

While the results presented in this study are encouraging, this was an analysis of a very small group of patients done in a retrospective manner. Survival and time to progression varied with a wide range of outcomes (albeit with a high average result).

Consult with your physician on local treatment options if your cancer progresses while undergoing treatment with an EGFR TKI drug (such as erlotinib or gefitinib).