The National Institute for Health and Care Excellence (NICE) has issued its final Technology Appraisal Guidance recommending Vargatef® (nintedanib) in combination with docetaxel as an option for use within the National Health Service (NHS).1
Nintedanib is the first triple angiokinase inhibitor licensed for the second-line treatment of advanced non-small cell lung cancer (NSCLC) of adenocarcinoma histology, in combination with docetaxel.2 This recommendation will come as a welcome decision to these patients, as it will provide them with an additional treatment option
Dr Charles De Wet, Medical Director, Boehringer Ingelheim UK and Ireland Ltd said “We are very pleased with NICE’s decision which confirms that Vargatef in combination with docetaxel is both clinically and cost effective for patients with non-small cell lung cancer of adenocarcinoma histology who have progressed on 1st line treatment. This is extremely good news for patients as the options in this setting are limited.”
Vargatef® (nintedanib) was granted European marketing authorisation on 21st November 2014 based on the international, randomised, double-blind, placebo controlled Phase III LUME-Lung I trial which compared nintedanib plus docetaxel, to placebo plus docetaxel in patients with locally advanced/metastatic or recurrent NSCLC after failure of first-line therapy.3
A retrospective analysis of the study results showed that patients of adenocarcinoma histology treated with nintedanib plus docetaxel had a significantly prolonged median progression free survival (primary endpoint) compared to those given placebo plus docetaxel (4.0 months versus 2.8 months respectively; p=0.0193). Median overall survival (secondary endpoint) which was analysed prospectively was significantly longer in those patients of adenocarcinoma histology treated with nintedanib plus docetaxel compared to placebo plus docetaxel (median 12.6 months versus 10.3 months respectively, p=0.0359) [2.3 month difference].3
There was no overall impact on global health or quality of life with the addition of nintedanib to docetaxel in patients with adenocarcinoma histology.4 The most common adverse events were gastrointestinal side effects and liver enzyme elevations which were managed with supportive treatment and / or dose reduction3 (adverse events nintedanib versus placebo: diarrhoea 43.4% vs 24.6%, ALT elevation 37.8% vs 9.3%, AST elevation 30.3% vs 7.2%, nausea 28.4% vs 17.7%, decreased appetite 23.4% vs 15.6% and vomiting 19.4% vs 12.3%)3. A higher frequency of neutropenia Grade > 3 was observed in the nintedanib plus docetaxel arm compared to docetaxel alone (50.3% versus 46.5% respectively), and subsequent complications such as febrile neutropenia (7.2% vs 4.5%)5 and sepsis (1.3% vs 0.6%)6 have been observed.
About the LUME-Lung 1 trial
LUME-Lung 1 is a randomised, double-blind, Phase III study comparing nintedanib plus docetaxel to placebo plus docetaxel in patients with locally advanced/metastatic or recurrent NSCLC after failure of first-line therapy. The study included 1,314 patients in Europe, Asia and South Africa, randomised to receive oral nintedanib 200 mg twice daily on days 2-21, plus docetaxel 75 mg/m2 on day 1 of each 3-week cycle (n=655) or matching placebo plus docetaxel (n=659). Patients were treated until disease progression or intolerable adverse events3.
Nintedanib is an oral triple angiokinase inhibitor that targets three growth factor receptor classes simultaneously: vascular endothelial growth factor receptors (VEGFR 1-3), platelet-derived growth factor receptors (PDGFR alpha and beta), and fibroblast growth factor receptors (FGFR 1-3).7 All three receptor classes have a key role in the formation and maintenance of new blood vessels (angiogenesis); their blockade may help to inhibit angiogenesis, which plays a critical role in tumour growth and spread.8,9
1. NICE Technology Appraisal Guidance. Nintedanib for previously treated locally advanced, metastatic, or locally recurrent non-small cell lung cancer. July 2015
2. Vargatef® 100 mg, 150 mg soft capsules. Summary of Product Characteristics 2015.
100 mg https://www.medicines.org.uk/emc/medicine/29790 last accessed April 2015
150 mg https://www.medicines.org.uk/emc/medicine/29791 last accessed April 2015
3. Reck M, Kaiser R Mellemgaard A et al. Docetaxel plus nintedanib versusdocetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial.Lancet Oncol 2014; 15: 143–55.
4. Novello S, Kaiser R, Mellemgaard A et al. Analysis of patient-reported outcomes from the LUME-Lung 1 trial: A randomised, double-blind, placebocontrolled, Phase III study of second-line nintedanib in patients with advanced non-small cell lung cancer. European Journal of Cancer 2014. Epub ahead of print.
5. Data on File ONC-14-48. Boehringer Ingelheim
6. Data on File ONC-14-49. Boehringer Ingelheim
7. Hillberg F, Roth GJ, Krssak M et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good anti-tumour efficacy. Cancer Res 2008; 68: 4774-82
8. Folkman N. Clinical applications of research on angiogenesis. N Engl J Med 1995; 333; 1757-63.
9. Bousquet C, Lamande N, Brand M et al. Suppression of angiogenesis, tumour growth and metastatis by adenovirus-mediated gene transfer of human angiotensinogen. Mol Ther 2006; 14: 175-82.
Source: Boehringer Ingelheim