CHICAGO—Nintedanib (BIBF 1120) in combination with docetaxel significantly prolonged progression-free survival (PFS) for all patients with metastatic non-small cell lung cancer (NSCLC) progressing after first-line chemotherapy regardless of histology, results from the LUME-Lung 1 trial reported in a presentation at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.

In addition, “a significant improvement in overall survival was demonstrated in patients with adenocarcinoma,” said Martin Reck, MD, of the Department of Thoracic Oncology, Grosshansdorf Hospital, Grosshansdorf, Germany.

The phase 3 randomized LUME-Lung 1 study randomly assigned patients with stage IIIB/IV or recurrent NSCLC to oral nintedanib 200 mg twice daily on days 2 through 21 plus docetaxel 75 mg/m2 intravenously on day 1 (n=655) or placebo plus docetaxel (n=659) in 21 day-cycles. The primary endpoint was centrally reviewed PFS after 713 events.

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Patients were stratified by Eastern Cooperative Oncology Group performance status 0 or 1, prior bevacizumab therapy, squamous versus nonsquamous histology, and brain metastases. Patient characteristics were balanced between treatment arms.

Dr. Reck reported that nintedanib plus docetaxel resulted in a median PFS of 3.4 months compared with 2.7 months for placebo plus docetaxel (hazard ratio [HR], 0.79; 95% CI: 0.68-0.92; P=0.0019) regardless of histology (squamous HR, 0.77; P=0.02; adenocarcinoma HR, 0.77; P=0.02).

Overall survival (OS) was significantly prolonged in all patients with adenocarcinoma in the nintedanib versus placebo arms—a median of 12.6 versus 10.3 months (HR, 0.83; P=0.0359)—with the greatest improvement observed in patients with adenocarcinoma whose time to study treatment was less than 9 months since start of first-line treatment, a median of 10.9 versus 7.9 months (HR, 0.75; P=0.0073). A trend for improved OS was seen in all patients in the nintedanib versus placebo arms: a median of 10.1 versus 9.1 months (HR, 0.94; P=0.272).

Disease control rates were significantly improved with nintedanib plus docetaxel in all patients with adenocarcinoma (odds ratio [OR], 1.93; P<0.0001), those with adenocarcinoma initiating first-line treatment within 9 months (OR, 2.90; P<0.0001), and all patients (OR, 1.68; P<0.0001).

The most common adverse events (AEs) were diarrhea and alanine transaminase elevations. Incidence of grade 3 or higher AEs was 71.3% in the nintedanib arm compared with 64.3% in the placebo arm. Withdrawals due to AEs were similar in both arms (22.7% vs. 21.7%), as were grade 3 or higher hypertension, bleeding, or thrombosis.

“Further investigations are warranted to identify molecular and clinical determinants of benefit for nintedanib in NSCLC,” Dr. Reck concluded.

The LUME-Lung 1 trial was funded by Boehringer Ingelheim.