New analysis of data from the LUME-Lung 1 Phase III clinical trial showed that the novel investigational compound nintedanib*, an oral triple angiokinase inhibitor that targets three receptors crucially involved in angiogenesis and tumour growth, provided a significant and clinically relevant overall survival benefit for advanced non-small cell lung cancer (NSCLC) patients with adenocarcinoma histology.(1)
The results were presented at the European Cancer Congress in Amsterdam.
“Adenocarcinoma is the most common form of non-small cell lung cancer and as the majority of patients with an advanced stage of the disease will ultimately progress after initial therapy, effective second-line treatments are vital,” said Dr. Anders Mellemgaard, Department of Oncology, Herlev University Hospital, Copenhagen. “Recent treatment advances for this sizeable patient population have been limited, but we have reached an important milestone with nintedanib. LUME-Lung 1 showed that nintedanib, when added to chemotherapy, was effective in extending overall survival by 2.3 months for advanced non-small cell lung cancer patients with adenocarcinoma histology and could become an important second-line option for these patients.”
LUME-Lung 1 showed nintedanib* plus docetaxel provided a statistically significant increase in median overall survival from 10.3 months in the placebo arm to 12.6 months in the nintedanib* arm (HR: 0.83, p-value: 0.04).(1) In addition, the data demonstrated that the earlier adenocarcinoma patients failed first line chemotherapy, the bigger the benefit that nintedanib* provided.(1) Compared to the overall adenocarcinoma patient population, patients with advanced adenocarcinoma who progressed within 9 months after start of their first-line treatment (T<9months) achieved a larger median overall survival benefit of 3 months (10.9 with nintedanib* plus docetaxel vs. 7.9 months with placebo plus docetaxel).(1)
The analysis of the overall survival benefit observed in adenocarcinoma T<9 months patients suggests T<9months to be a predictive clinical biomarker of nintedanib* benefit in second-line, advanced NSCLC patients with adenocarcinoma histology.(1,2)
The most common adverse events (AEs) in LUME-Lung 1 were gastrointestinal side effects and reversible liver enzyme elevations which were manageable by supportive treatment or dose reduction (adverse events placebo vs. nintedanib*: nausea 18% vs. 24%, vomiting 9% vs. 17%, diarrhoea 22% vs. 42% and liver enzyme elevation 8% vs. 29%). Withdrawal due to adverse events was similar in both arms, as were Grade 3, bleeding or thromboembolic events.(1) The trial results demonstrated that despite the observed adverse events, patients benefited from the additional efficacy of nintedanib*, when added to docetaxel, without significantly further impacting their quality of life.
Boehringer Ingelheim endeavours to make nintedanib* available to patients around the world. Submissions worldwide are currently under preparation.
*Nintedanib and volasertib are investigational compounds and are not yet approved. Their safety and efficacy has not yet been fully established.
- Mellemgaard A, Kaiser R, Douillard J-Y et al. Analysis of overall survival in adenocarcinoma NSCLC patients receiving 2nd line combination treatment with nintedanib (BIBF-1120) + docetaxel in the LUME-Lung 1 trial: a randomised, double-blind, placebo-controlled phase 3 study. Oral presentation on 29 September 2013 at 09.00 at The European Cancer Congress 2013 Abstract. no 3409.
- Kaiser R, Barrueco J, Reck M et al. Identification of a clinical biomarker for 2nd line combination with nintedanib in adenocarcinoma non-small cell lung cancer (NSCLC) patients in two phase III trials. Poster presentation on 29 September 2013 at 14.00 at The European Cancer Congress 2013. Abstract no. 3479.
- Hilberg F, Roth GJ, Krssak M, et al. BIBF1120: triple angiokinase inhibitor with sustained receptor blockade and good anti-tumor efficacy. Cancer Res 2008;68: 4774-82.
- Folkman N. Clinical applications of research on angiogenesis. N Engl J Med 1995;333: 1757-63.
- Bousquet C, Lamande N, Brand M, et al. Suppression of angiogenesis, tumor growth, and metastasis by adenovirus-mediated gene transfer of human angiotensinogen. Mol Ther 2006;14:175-82.
- Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917.
- Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2010, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2010/, based on November 2012 SEER data submission, posted to the SEER web site, 2013.