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Nintedanib in combination with docetaxel is an effective second-line option for patients with advanced non-small cell lung cancer previously treated with one line of platinum-based therapy, according to the results of a study published in The Lancet Oncology.

Lung cancer remains the leading cause of cancer death in the United States. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Currently available combination chemotherapy regimens can improve the duration of survival as well as quality of life, but researchers continue to search for ways to improve outcomes for patients with this disease—including treatment with targeted therapies.

Nintedanib is an angiokinase inhibitor targeting pathways mediated by VEGFR 1-3, FGFR 1-3, and PDGFR ? and ?; it also reportedly inhibits receptor kinases of RET, FLT3, and the Src family.

The phase 3 LUME-Lung 1 was a placebo-controlled, double-blind study that assessed the efficacy and safety of docetaxel plus nintedanib as second-line therapy for NSCLC. The study included 1,314 patients from 211 centers in 27 countries with stage IIIB/IV recurrent NSCLC that had progressed after first-line chemotherapy. Patients were randomly assigned to receive docetaxel plus nintedanib or docetaxel plus placebo. The primary endpoint was progression-free survival and a secondary endpoint was overall survival.

After a median follow-up of 7.1 months, median progression-free survival was significantly longer in the group receiving docetaxel plus nintedanib (3.4 months) compared with the group receiving placebo (2.7 months). The effect of nintedanib was seen even after adjusting for age, smoking status, performance status, and other characteristics.

After progression, 48 percent of patients with squamous cell carcinoma and 56 percent of those with adenocarcinoma received subsequent treatment. After a median follow-up of 31.7 months, median overall survival was significantly longer in the patients receiving the combination nintedanib/docetaxel treatment, as follows:

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  • With adenocarcinoma (12.6 vs 10.3 months)
  • With adenocarcinoma that progressed within 9 months after start of first-line treatment (10.9 vs 7.9 months)

The same did not hold true for the total study population—median overall survival was 10.1 months for the combination group and 9.1 months for the placebo group.

Grade 3 or higher adverse events were more common in the nintedanib group and included diarrhea, increased alanine aminotransferase (ALT), and increased aspartate aminotransferase (AST). Adverse events led to dose reductions in 19 percent of the nintedanib group and 6 percent of the placebo group. Adverse events led to discontinuation of study treatment in 23 percent of nintedanib/docetaxel patients and 22 percent of docetaxel/placebo patients. Adverse events led to death considered possibly unrelated to disease progression in 5.4 percent of the combination group and in 3.8 percent of the docetaxel group—events included sepsis (5 combination patients vs. 1 placebo), pneumonia (2 vs. 7), respiratory failure (4 vs. 0), and pulmonary embolism (0 vs. 3).

The researchers concluded that “nintedanib in combination with docetaxel is an effective second-line option for patients with advanced NSCLC previously treated with one line of platinum-based therapy, especially for patients with adenocarcinoma.” The combination significantly improved progression-free survival in all patients and improved overall survival in patients with adenocarcinoma.


Reck M, Kaiser R, Mellemgaard A, et al: Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. The Lancet Oncology. 2014; 15(2): 143-155.

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