Outcomes Associated with Brain Metastases in a Three-Arm Phase III Trial of Gemcitabine-Containing Regimens Versus Paclitaxel Plus Carboplatin for Advanced Non-small Cell Lung Cancer

Background: Brain metastases (BMs) are a common complication of non-small cell lung cancer (NSCLC). Because of historical data indicating a poor prognosis for patients with BM, few randomized phase III studies of advanced NSCLC have included patients with BM at presentation. Because the potential benefits of systemic therapy in patients with BM are uncertain, we analyzed data from a recent phase III study. Methods: One thousand one hundred thirty-five chemonaive patients with stage IIIB/IV NSCLC were randomized to receive gemcitabine/carboplatin, gemcitabine/paclitaxel, or paclitaxel/carboplatin. Stratification was based on presence or absence of BM, stage, and baseline weight loss. Patients with BM were required to be clinically stable after treatment with radiotherapy or surgery before entry. Results were retrospectively analyzed by presence or absence of BM at study entry. Results: Rate of BM was 17.1% overall. The response rate was 28.9% for patients with BM (n = 194) versus 29.1% without BM (n = 941). Time to progression was 4.3 months with BM and 4.6 months without BM (p = 0.03). Median survival was 7.7 months (95% confidence interval: 6.7-9.3) among patients with BM (n = 194) and 8.6 months (95% confidence interval: 7.9-9.5) for patients without BM (n = 941), p = 0.09. Rates of hematologic adverse events were not different among patients with and without BM. Conclusions: There were no significant differences in response, survival, or hematologic toxicity for patients with or without BM; however, patients with BM had a small but significantly shorter time to progression. Nonprogressing patients with treated BM are appropriate candidates for systemic therapy and entry into clinical trials.