What is the best second-line treatment for metastatic non-small-cell lung cancer patients?

This study compared the safety and efficacy of two second-line treatments for non-small cell lung cancer patients that have wild-type (normal, not mutated) epidermal growth factor receptor (EGFR).

For patients with advanced, metastatic non-small-cell lung cancer (cancer that has spread beyond the lung to other areas of the body), platinum-based chemotherapy is the first-line treatment option. Second-line treatments include docetaxel (Taxotere, another form of chemotherapy), pemetrexed (Alimta, also another chemotherapy), and erlotinib (Tarceva, an EGFR-tyrosine kinase inhibitor).

Some lung cancers can be caused by a mutation in the EGFR gene, which causes increased growth and spread of cancer cells. By blocking EGFR with treatments such as erlotinib, the increased growth is blocked. However, it is not known whether treatments such as erlotinib can be helpful in the majority of non-small cell lung cancer patients who have wild-type EGFR. 

The current study compared erlotinib to docetaxel as second-line treatments for metastatic non-small-cell lung cancer patients with wild-type EGFR. The study randomly assigned 222 patients to receive either docetaxel (110 patients) or erlotinib (112 patients). Docetaxel was delivered intravenously (into the vein) either once every 21 days (75 mg/m2) or on days 1, 8, and 15 of a 28-day cycle (35 mg/m2). Erlotinib was given orally once a day (150 mg). Overall survival (time from treatment until death from any cause), progression-free survival (time from treatment until disease progression), and disease control (slowing or stopping of tumor growth) rates were measured. Toxicity (negative side effects) was also measured and drug doses were decreased if necessary. Patients were followed for an average of 33 months.

The average overall survival time was 8.2 months for those receiving docetaxel, compared to 5.4 months for those receiving erlotinib. The average 1 year survival rate was 39.6% for patients receiving docetaxel, and 31.8% for those receiving erlotinib. Progression free survival rates after 6 months of treatment were 27.3% for the docetaxel group and 16.5% the erlotinib group. After disease progression the average survival time was 3.2 months for docetaxel and 2.5 months for erlotinib patients. A significantly higher percentage of patients receiving docetaxel achieved disease control (44.3%) compared to the erlotinib group (26%).

Treatment delays were necessary in 17% of patients receiving docetaxel and 18% of patients receiving erlotinib due to toxicity. Common side effects in the docetaxel group included neutropenia (low white blood cell levels), nausea, and alopecia (hair loss), while patients receiving erlotinib experienced a higher number of skin-related side effects.

This study concluded that chemotherapy is the more effective second-line treatment for metastatic non-small cell lung cancer patients with wild-type EGFR.

Though this research was published in Sep 2013, we feel that it is still relevant. Erlotinib is an EGFR inhibitor, meaning it should be most active in cancers where the EGFR protein is mutated. This article is relevant as it examines the action of the drug in patients who do not have an EGFR mutation, explaining why it is not the most suitable drug for use in these patients.