Determining the most effective first-line treatment in EGFR positive metastatic lung adenocarcinoma

This study compared two treatment options for patients with epidermal growth factor receptor (EGFR) mutation-positive metastatic non-small cell lung cancer (non-small-cell lung cancer that has an abnormal EGFR gene and has spread to distant sites).

One possible cause of non-small cell lung cancer is a mutation in the gene that controls the production of the EGFR. An increase in EGFR can lead to an increase in tumor cell production and spread, therefore a main treatment for patients with this mutation is to inhibit (block) the activity of EGFR. Treatment with EGFR inhibitors, such as afatinib (Gilotrif), can improve progression-free survival (time following treatment before the disease progresses) compared to treatment with chemotherapy. However, the majority of previous trials comparing the two treatments have used platinum-based chemotherapies, along with two other forms of chemotherapy, taxanes (such as paclitaxel [Taxol] or docetaxel [Taxotere]) or gemcitabine (Gemzar).

Pemetrexed (Alimta) has recently become a chemotherapy treatment of choice in patients with non-squamous non-small cell lung cancer, as studies have shown it to improve tumor response and survival times compared to taxanes or gemcitabine. Pemetrexed has not yet been compared to EGFR inhibitors as first-line treatment for patients with EGFR mutation-positive non-small cell lung cancer. 

The current study compared the effects of pemetrexed to afatinib in patients with EGFR mutation-positive metastatic non-small cell lung cancer. This study included 340 patients randomly assigned to receive afatinib (once a day for an average of 11 months) or chemotherapy (cisplatin [Platinol] plus pemetrexed) every 21 days for up to six cycles. The average follow-up time was 16.4 months.

Progression-free survival was significantly longer for patients receiving afatinib (average of 11.1 months) compared to those receiving pemetrexed (average of 6.9 months). Significantly higher response rates (such as tumor shrinkage) were also found in patients receiving afatinib (56%) compared to pemetrexed (23%). Time until symptom return (such as cough or shortness of breath) was between 32% and 40% longer for patients receiving afatinib.

The most common treatment related adverse events were diarrhea (95.2%), rash/acne (89.1%), and stomatitis (mouth sores; 72.1%) for afatinib and nausea (65.8%), fatigue (46.8%), and decreased appetite (53.2%) for chemotherapy.

This study concluded that afatinib led to significant benefits in progression-free survival and response rates compared to chemotherapy in patients with metastatic non-small-cell lung cancer.