Survival Outcomes According to TIMP1 and EGFR Expression in Heavily Treated Patients with Advanced Non-small Cell Lung Cancer who Received Biweekly Irinotecan Plus Bevacizumab

Abstract

Background: Heavily treated patients with non-small cell lung cancer (NSCLC) have few treatment options, while irinotecan and bevacizumab have proven synergistic action in preclinical studies.

Patients and methods: A total of 49 patients with heavily treated NSCLC were enrolled from 2011-2014 and treated with irinotecan and bevacizumab. Treatment response along with mutational status of epidermal growth factor receptor (EGFR), and tissue inhibitor of metalloproteinases-1 (TIMP1) and EGFR expression were evaluated. Progression-free (PFS) and overall (OS) survival were monitored.

Results: Median follow-up was 13.2 months. Twenty-three patients had received three or more prior therapy lines. Overall response rate was 32% [95% confidence interval (CI)=22%-39%] and 26% of patients achieved stable disease. Median PFS was 4.4 (95% CI=2.8-8.3) months and median OS 18.0 (95% CI=16.2-30.7) months. Nine patients harboring EGFR mutations had a long-lasting partial response. A shorter OS was found in patients with a higher TIMP1 expression (p=0.006).

Conclusion: Irinotecan combined with bevacizumab had favorable antitumor activity in heavily pretreated patients with NSCLC. These results suggest this is a reasonable strategy, particularly for patients with low TIMP1 expression.

Keywords: EGFR mutation; Irinotecan; TIMP1; bevacizumab; gene expression.