Nintedanib (BIBF 1120) plus docetaxel in NSCLC patients progressing after first-line chemotherapy: LUME Lung 1, a randomized, double-blind phase III trial.

Lung Cancer - Non-Small Cell Metastatic
Session Type and Session Title: 
Clinical Science Symposium, Targeted Therapies in Lung Cancer: What's New and What's Enough?
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr LBA8011)
Martin Reck, Rolf Kaiser, Anders Mellemgaard, Jean Yves Douillard, Sergey Orlov, Maciej Jerzy Krzakowski, Joachim Von Pawel, Maya Gottfried, Igor Bondarenko, Meilin Liao, Jose Barrueco, Birgit Gaschler-Markefski, Silvia Novello; Department of Thoracic Oncology, Grosshansdorf Hospital, Grosshansdorf, Germany; Boehringer Ingelheim GmbH, Biberach, Germany; Department of Oncology, Herlev University Hospital, Herlev, Denmark; Department of Medical Oncology, Centre René Gauducheau, Nantes, France; Department of Thoracic Oncology, St. Petersburg State Medical University, St. Petersburg, Russia; The Maria Sklodowska-Curie Institute of Oncology, Warsaw, Poland; Pneumology Clinic, Asklepios Fachkliniken Gauting, Munich, Germany; Lung Cancer Unit, Meir Medical Center, Kfar-Saba, Israel; Municipal Institution Dnipropetrov, Dnipropetrovsk, Ukraine; Shandong Provincial Chest Hospital, Shanghai, China; Boehringer Ingelheim GmbH, Ridgefield, CT; Department of Oncology, University of Turin, Turin, Italy

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Abstract Disclosures


Background: Nintedanib (N) inhibits VEGFRs, PDGFRs, and FGFRs. LUME Lung 1 is a placebo (P) controlled phase III trial of N + docetaxel (D) in patients (pts) with locally advanced/metastatic NSCLC progressing after first-line therapy. Methods: Stage IIIB/IV or recurrent NSCLC pts (stratified by histology, ECOG PS, prior bevacizumab, and brain metastases) were randomized to N 200 mg bid + D 75 mg/m2 q21d (n=655) or P + D (n=659). 1° endpoint was centrally reviewed PFS after 713 events (2 sided stratified log-rank, α=5%, β=10%). Key 2° endpoint of OS was analyzed hierarchically after 1,121 events (2 sided, adjusted α=4.98%, β=20%), first in adenocarcinoma (adeno) pts <9 mo since start of first-line therapy (T<9mo; identified as a prognostic/predictive biomarker [ASCO ‘13]), followed by all adeno pts and then all pts. Predefined sensitivity analyses added sum of longest diameters of target lesions (SLD) to stratification factors in the Cox model. Results: Pt characteristics were balanced between the arms. N + D significantly prolonged PFS vs P + D (HR 0.79; CI: 0.68, 0.92; p=0.0019; median 3.4 vs 2.7 mo) regardless of histology (squamous HR 0.77, p=0.02; adeno HR 0.77, p=0.02). OS was significantly prolonged in all adeno pts (HR 0.83; p=0.0359; median 12.6 vs 10.3 mo) with the greatest improvement seen in T<9mo adeno pts (HR 0.75; p=0.0073; median 10.9 vs 7.9 mo). A trend for improved OS was seen in all pts (HR 0.94; p=0.272; median 10.1 vs 9.1). When adjusted for SLD, a significant OS benefit was seen in all pts (HR 0.88; CI: 0.78, 0.99; p=0.0365). Disease control rates were significantly improved with N + D in all adeno pts (odds ratio [OR] 1.93; p<0.0001), T<9mo adeno pts (OR 2.90; p<0.0001) and all pts (OR 1.68; p<0.0001). 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%). Incidence of CTCAE Gr ≥3 AEs was 71.3 vs 64.3%. Withdrawals due to AEs (22.7 vs 21.7%) were similar in both arms, as were Gr ≥3 hypertension, bleeding or thrombosis. Conclusions: N + D significantly improved PFS independent of histology, and prolonged OS for adeno pts. AEs were generally manageable with dose reductions and symptomatic treatment. Clinical trial information: NCT00805194.