ASCO 2013 Abstract LBA#8011 - LUME Lung 1, a Randomized, Double-Blind Phase III Trial

Abstract LBA8011: Nintedanib (BIBF 1120) Plus Docetaxel in NSCLC Patients Progressing After First-Line Chemotherapy: LUME Lung 1, a Randomized, Double-Blind Phase III Trial
Martin Reck et al.

LUME 1: The Light is On in Second Line Non Small Cell Lung Carcinoma

Antiangiogenesis as a target has been disappointing in NSCLC. Trials with angiokinase inhibitors have failed either as single agents or combined with chemotherapy. Until now.

LUME 1 studied nintedanib, an oral triple angiokinase inhibitor (TKI) inhibiting VEGFR, FGFR and PDGFR.  In this study, over 1200 patients with advanced NSCLC of all histologies were randomized in the second line setting to ninetedanib (N) 200 mg bid + docetaxel (D) 75 mg/m2q21d (n = 655) or docetaxel (D)alone (n = 659). The 1° endpoint was progression free survival (PFS).

Nintedanib with docetaxel significantly prolonged PFS vs docetaxel alone, median 3.4 vs. 2.7 mo (HR 0.79, p = 0.0019 regardless of histology (Figure 1). Overall survival (OS) was significantly prolonged in patients with adenocarcinoma histology 12.6 vs. 10.3 months (HR 0.83; p = 0.0359;)(Figure 2). A trend for improved OS was seen in all median 10.1 vs. 9.1 months (HR 0.94; p = 0.272). The most common AEs were diarrhea (any: 42.3 vs. 21.8%; Gr ≥ 3: 6.6 vs. 2.6%) and ALT elevations (any: 28.5 vs. 8.4%; Gr ≥ 3: 7.8 vs. 0.9%). Grade ≥ 3 adverse events of special interest, hypertension, bleeding or thrombosis, were similar in both arms.

Figure 1

Figure 1

Figure 2

Figure 2

How strong is the light? The primary endpoint of PFS was improved only slightly but was statistically significant. More interesting is the improvement of two months in overall survival of patients with adenocarcinoma. A survival of over one year in a second line trial is encouraging.

A light has been turned back on for antiangiogenesis in NSCLC.