Gefitinib plus chemotherapy improves survival outcomes in mutated NSCLC brain metastases

Treatment with the combination of gefitinib and chemotherapy appears to yield significant increases in progression-free survival (PFS), intracranial PFS, and overall survival (OS) in patients with untreated EGFR-mutant non-small cell lung cancer (NSCLC) brain metastases as compared gefitinib monotherapy, according to the results of the phase III GAP BRAIN study.

GAP BRAIN included 161 patients (mean age 55 years, 54.0 percent women) who were randomly assigned to receive gefitinib (n=81) or gefitinib plus chemotherapy (pemetrexed with platinum; n=80). The primary endpoint was intracranial PFS, while secondary endpoints included PFS, OS, intracranial objective response rate, overall objective response rate, and safety. The median follow-up time was 21.1 months.

In the intention-to-treat analysis, the median intracranial PFS was significantly longer with gefitinib plus chemotherapy than with gefitinib monotherapy (15.6 vs 9.1 months; hazard ratio [HR], 0.36, 95 percent confidence interval [CI], 0.25–0.53; p<0.001).

Likewise, the combination was associated with significantly better median PFS (16.3 vs 9.5 months; p<0.001), intracranial objective response rate (85.0 percent vs 63.0 percent; p=0.002), and overall objective response rate (80.0 percent vs 64.2 percent; p=0.03) compared with monotherapy.

At data cutoff, the median OS was also significantly more favourable with gefitinib plus chemotherapy group vs gefitinib alone (35.0 vs 28.9 months; HR, 0.65, 95 percent CI, 0.43–0.99; p=0.04).

In terms of safety, the frequency of grade 3 or worse adverse events was higher with gefitinib plus chemotherapy, although most of the events were manageable.

The findings suggest that gefitinib plus chemotherapy could be an optional first-line treatment for patients with untreated EGFR-mutant NSCLC brain metastases.