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

Abstract

OBJECTIVES:

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.

• Authors: Martin Reck, Anders Mellemgaard, Joachim von Pawel, Maya Gottfried, Igor Bondarenko, Ying Cheng, Kostas Zarogoulidis, Alexander Luft, Jaafar Bennouna, José Barrueco, Hesham Aboshady, Julia Hocke, Rolf Kaiser, Jean-Yves Douillard, LUME-Lung 1 Study Group
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 90 Issue 2 Pg. 267-73 (Nov 2015) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 26415992 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Indoles
• Taxoids
• Docetaxel
• nintedanib

Topics

• Adenocarcinoma (drug therapy)
• Angiogenesis Inhibitors (adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Carcinoma, Squamous Cell (drug therapy)
• Disease-Free Survival
• Docetaxel
• Humans
• Indoles (administration & dosage, adverse effects)
• Lung Neoplasms (drug therapy)
• Taxoids (administration & dosage, adverse effects)
• Treatment Outcome