Appendix Methods and Materials, Tables 1-4, Figures 1-3. Appendix Table 1: Characteristics of patients at baseline Appendix Table 2: Best response rates for primary tumors and metastases in 24 patients treated with second-line bevacizumab plus erlotinib Appendix Table 3: PFS, OS, and response rates according to EGFR mutation status in 24 patients treated with second-line bevacizumab plus erlotinib Appendix Table 4: Overview of AEs in 24 patients treated with second-line bevacizumab plus erlotinib Appendix Figure 1. Response rates for patients treated with second-line bevacizumab plus erlotinib. Appendix Figure 2. Waterfall plots of best overall response for patients treated with second-line bevacizumab plus erlotinib. Appendix Figure 3. Kaplan-Meier curves for second-line treatment with bevacizumab plus erlotinib.
ARTICLE ABSTRACTPurpose: The phase II prospective, noncomparative BRAIN study (NCT00800202) investigated efficacy and safety of bevacizumab in chemotherapy-naïve or pretreated patients with non–small cell lung cancer (NSCLC) and asymptomatic untreated brain metastases to provide data in this previously unexplored subgroup.Experimental Design: Patients with stage IV nonsquamous NSCLC, Eastern Cooperative Oncology Group performance status 0–1, and untreated, asymptomatic brain metastases received first-line bevacizumab (15 mg/kg) plus carboplatin (area under the curve ×6) and paclitaxel (200 mg/m2) every 3 weeks (B + CP), or second-line bevacizumab plus erlotinib (150 mg/d; B + E). Six-month progression-free survival (PFS) was the primary endpoint. The trial could be stopped if there were more than three (B + CP) or more than two (B + E) intracranial hemorrhages.Results: In first-line B + CP cohort (n = 67), 6-month PFS rate was 56.5% with a median PFS of 6.7 months [95% confidence interval (CI), 5.7–7.1] and median overall survival (OS) of 16.0 months. Investigator-assessed overall response rate (ORR) was 62.7%: 61.2% in intracranial lesions and 64.2% in extracranial lesions. Because of low enrolment (n = 24), efficacy results for the second-line B + E cohort were exploratory only; 6-month PFS rate was 57.2%, median PFS was 6.3 months (95% CI, 3.0–8.4), median OS was 12.0 months, and ORR was 12.5%. Adverse events were comparable with previous trials of bevacizumab. One grade 1 intracranial hemorrhage occurred and resolved without sequelae.Conclusions: The BRAIN study demonstrates encouraging efficacy and acceptable safety of bevacizumab with first-line paclitaxel and carboplatin in patients with NSCLC and asymptomatic, untreated brain metastases. Clin Cancer Res; 21(8); 1896–903. ©2015 AACR.