This study aimed to determine the efficacy of a combination of the anticancer drugs afatinib (Gilotrif) and paclitaxel (Taxol) to treat non-small cell lung cancer (NSCLC), compared to chemotherapy alone. The study found that a combination of these drugs significantly improved progression free survival (PFS, time from treatment until disease progression) and overall response rate (ORR, number of patients whose tumor size decreased by at least 50%). 

A mutation (change) in the epidermal growth factor receptor (EGFR) can lead to non-small cell lung cancer (NSCLC). EGFR-mutant-NSCLC responds better to treatments that block EGFR, such as gefitinib (Iressa) and erlotinib (Tarceva), than other chemotherapies. However, patients often develop resistance to both drugs and disease progresses.

In these patients, tumors may still have some cells that will respond to EGFR blockers. Because of this, it may be useful to continue using EGFR blockers as part of treatment. Afatinib is an EGFR blocker that has been shown to be effective in treating EGFR-mutant-NSCLC. It is not clear whether afatinib would be more effective in combination with a chemotherapy drug, such as paclitaxel.

This study compared whether afatinib would be more effective with or without a chemotherapy agent in EGFR-mutant NSCLC patients whose disease had progressed despite treatment.

There were two parts to this study. Part A included 1154 patients who had stage 3b or 4 NSCLC (spread to the lymph nodes or beyond) that had progressed despite chemotherapy and erlotinib or gefitinib. Patients were treated with afatinib for 12 weeks. Any patients who responded to afatinib were included in part B.

Part B included 192 patients. 132 of these were treated with a combination of afatinib and paclitaxel (group 1) and 60 were treated with chemotherapy alone (group 2).

Patients in group 1 experienced significantly longer PFS (an average of 5.6 months) compared to group 2 (average of 2.8 months). The ORR was also significantly higher in group 1 (32.1%) compared to group 2 (13.2%). There was no difference in overall survival (time from treatment until death from any cause) between the groups.

88.6% of group 1 and 70% of group 2 experienced treatment-related side effects. The most common side effects in group 1 were diarrhea, hair loss, and lack of energy. Common effects in group 2 included lack of energy, decreased appetite, and nausea. 48.5% of patients in group 1 and 30% of patients in group 2 experienced more severe side effects, including low white blood cell levels (cells that help fight infection).

This study concluded that a combination of afatinib and paclitaxel may be more effective than chemotherapy alone in some EGFR-mutant-NSCLC patients who are resistant to erlotinib or gefitinib. 

This study was mainly funded by Boehringer Ingelheim, the manufacturers of afatinib.

Discuss this dual combination of afatinib and paclitaxel with your doctor if your disease has progressed following gefitinib and erlotinib.