Dr. Wakelee on Nintedanib Plus Chemotherapy in NSCLC

Heather Wakelee, MD, an assistant professor at the Stanford University School of Medicine and member of the Stanford Cancer Institute, describes two phase III trials presented at the 2013 ASCO Annual Meeting that focused on the second-line administration of the oral triple angiokinase inhibitor nintedanib (BIBF 1120) plus chemotherapy to treat patients with advanced non-small cell lung cancer (NSCLC).

The LUME-Lung 1 trial enrolled patients with NSCLC with squamous and adenocarcinoma histology and found that the addition of nintedanib to docetaxel extended median progression-free survival (PFS) from 2.7 months to 3.4 months (HR = 0.79; CI: 0.68, 0.92; P = .0019). The overall survival (OS) benefit was not significant, Wakelee notes. However, in the adenocarcinoma subset of the trial, OS was significantly prolonged from 10.3 months to 12.6 months with the addition of nintedanib (HR = 0.83; P = .0359).

Several trials have examined a VEGFR TKI in combination with chemotherapy in the first- and second-lines of treatment for NSCLC, notes Wakelee. However, none of these trials demonstrated a statistically significant improvement in OS. As a result, the significant improvement in OS within the adenocarcinoma subset is intriguing, Wakelee believes.

All the same, the LUME-Lung 2 trial adds confusion to these findings, Wakelee points out. In this trial, patients with purely adenocarcinoma histology received pemetrexed plus nintedanib. PFS was significantly prolonged but no difference was observed for OS. The lack of an OS benefit could be the result of an early DMC futility analysis predicting a lack of benefit in PFS, believes Wakelee. As a result of this analysis patient accrual was halted and the study was unblinded. Despite this, the trial was capable of fulfilling its primary endpoint of PFS but remained underpowered to demonstrate an OS benefit.