Anti-angiogenic-specific adverse events in patients with non-small cell lung cancer treated with nintedanib and docetaxel

Lung Cancer, November 2015, Volume 90, Issue 2, Pages 267-273



  • The combination of nintedanib/docetaxel was evaluated in LUME-Lung 1.

  • Adverse events (AEs) seen with existing anti-angiogenic agents were evaluated.

  • AEs associated with other agents were less pronounced with nintedanib + docetaxel.




LUME-Lung 1 was a randomized, placebo-controlled, Phase III trial investigating nintedanib + docetaxel versus placebo + docetaxel in patients with advanced NSCLC progressing after first-line chemotherapy. Progression-free survival was significantly improved with nintedanib + docetaxel in the overall population and overall survival was significantly improved in the pre-specified analysis of patients with adenocarcinoma. We evaluated the frequency of characteristic adverse events (AEs) commonly seen with existing anti-angiogenic agents.

Materials and methods

The incidence and intensity of AEs were evaluated in all patients who received at least one dose of study medication ( N = 1307) and for the two main histologies: adenocarcinoma ( n = 653) and squamous cell carcinoma (SCC; n = 553). AEs of special interest were analyzed by category, preferred term, and worst CTCAE grade and included perforation, hypertension, bleeding, thromboembolic events, and skin disorders.

Results and conclusion

The incidence of patients with all-grade gastrointestinal (GI) perforations was low and balanced between arms (0.5% in both) and across histologies; the incidence of non-GI perforations was 1.2% with nintedanib + docetaxel versus 0.2% with placebo + docetaxel. The incidence of some events was higher with nintedanib + docetaxel versus placebo + docetaxel; hypertension (3.5% vs 0.9%), rash (11.0% vs 8.1%), and cutaneous adverse reactions (13.0% vs 10.7%). Rash and cutaneous adverse reactions were predominantly Grade 1–2 with both treatments. The incidence of all-grade bleeding was also slightly higher in nintedanib + docetaxel-treated patients (14.1% vs 11.6%) driven by between-treatment differences in the SCC subpopulation; most events were Grade 1–2. The proportion of patients with a thromboembolic event was low and comparable between arms for all grades (5.1% vs 4.6%) and Grade ≥3 (2.1% vs 3.1%). Safety evaluation of the LUME-Lung 1 study showed that the frequency of AEs commonly associated with other anti-angiogenic agents was lower with nintedanib + docetaxel. Survival benefits from addition of nintedanib to docetaxel in patients with adenocarcinoma after first-line therapy can be achieved alongside a manageable safety profile.

Keywords: Non-small cell lung cancer, Angiogenesis inhibitors, Drug-related side effects and adverse reactions.