Should all patients receive EGFR inhibitors?

This study examined the use of sequential chemotherapy and erlotinib as a first-line treatment for non-small cell lung cancer.

Certain genetic mutations, for example in the epidermal growth factor receptor (EGFR; a protein found on the surface of cells in the body), can often play a role in the growth of non-small cell lung cancer. For these patients the best treatment includes therapies that target the mutation, such as EGFR tyrosine-kinase inhibitors, which block the activity of the epidermal growth factor receptor, slowing tumor growth.

However, careful testing is needed to determine the mutation status, and many patients may not know their status at the time of treatment choice. While all patients could be treated with both chemotherapy and an EGFR tyrosine-kinase inhibitor at the same time, regardless of mutation status, studies have not found this to necessarily improve survival. Other studies, however, have found that using the two treatments sequentially (chemotherapy followed by an EGFR tyrosine-kinase inhibitor), increased progression-free survival time (time from treatment until disease progression).

The current study compared progression-free survival in non-small cell lung cancer patients receiving chemotherapy followed by an EGFR tyrosine-kinase inhibitor compared to chemotherapy alone. 451 patients with advanced or metastatic non-small cell lung cancer (cancer that has spread beyond the lung) were randomly assigned to receive 6 cycles of platinum-based chemotherapy (for example cisplatin) followed by erlotinib (Tarceva, an EGFR tyrosine-kinase inhibitor) or a placebo (a substance with no effect on the body used as a comparison). The study was mainly looking at progression-free survival. Overall survival and objective response rates (a noticeable change in the tumor, such as tumor shrinkage) were also measured. The average follow-up time was 28 months.

Overall, average progression-free survival was significantly longer in the erlotinib group (7.6 months) compared to the placebo group (6.0 months). The average overall survival time was 18.3 months for the erlotinib group and 15.2 months for the placebo group, a significant decrease. 43% of the patients in the erlotinib group showed an objective response to treatment, compared to 18% of those in the placebo group.

53% of the patients were tested for EGFR mutation status; 40% of those patients were EGFR mutation positive. For those patients, progression-free survival was 16.8 months in the erlotinib group and 6.9 months in the placebo group. Average overall survival was 31.4 months with erlotinib and 20.6 months with placebo. Patients without the EGFR mutation did not see significant differences in progression-free survival, overall survival, or objective responses with the two treatments. Patient with unknown mutation status saw a significant improvement in progression-free survival following erlotinib treatment (7.1 months) compared to placebo (6.0 months), indicating that some of these patients did have the EGFR mutation.

Erlotinib led to more adverse effects that did placebo, including higher rates of skin rash and diarrhea.

This study concluded that chemotherapy followed by an epidermal growth factor receptor tyrosine-kinase inhibitor is a beneficial treatment option for patients with EGFR-positive non-small cell lung cancer.