What is the optimal treatment for lung cancer that has not responded to chemotherapy?

This analysis compared the safety and efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors and chemotherapy as second-line treatments for lung cancer that has progressed despite first-line chemotherapy.

The first-line (primary) treatment for the majority of lung cancer patients is chemotherapy, but the disease often progresses regardless. While other forms of chemotherapy are used as second-line treatments, the newer epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib (Tarceva) and gefitinib (Iressa), have also been approved.

There is no consensus yet on whether EGFR-TKIs or a second type of chemotherapy are more beneficial as second-line treatments. It is also unclear whether EGFR-TKIs are useful for patients whose lung cancer was not due to a mutation in the epidermal growth factor receptor gene. The current meta-analysis (a review of multiple studies examining the same research question) explored which is the optimal second-line treatment for lung cancer, and whether the optimal treatment depends on EGFR mutation status.

Ten studies were analyzed, including 3825 patients: 1905 received an EGFR-TKI, and 1920 received chemotherapy. Each study compared the chemotherapy agents docetaxel (Taxotere) or pemetrexod (Alimtra) and the EGFR-TKIs gefitinib and erlotinib.

Overall, there was no significant differences between the treatments in terms of progression-free survival (time following treatment before disease progression), overall survival, or objective response (a measurable response such as tumor shrinkage).

Chemotherapy led to a 35% increase in progression-free survival in patients who were EGFR mutation negative, compared to EGFR-TKIs. EGFR mutation positive patients had an 80% longer progression-free survival when using EGFR-TKIs compared to chemotherapy. No significant difference was seen in overall survival.

EGFR-TKIs led to 7 times the number of serious skin rashes compared to chemotherapy, but had a 55% smaller risk of fatigue or low white blood cell counts (which corresponds to a decrease in the immune systems’ ability to fight infection) compared to chemotherapy.

This study determined that while second-line chemotherapy is optimal for patients who are EGFR mutation negative, for those patients with the EGFR mutation epidermal growth factor receptor-tyrosine kinase inhibitors can be more effective.