A potential new drug being developed by Boehringer Ingelheim, nintedanib, is being investigated as a potential treatment for a range of different solid tumour types
Angiogenesis is a common target for cancer therapy. A potential new drug being developed by Boehringer Ingelheim, nintedanib, hits three different receptor tyrosine kinases involved in the regulation of angiogenesis: fibroblast growth factor receptor; platelet-derived growth factor; and vascular endothelial growth factor receptor.1 It is being investigated as a potential treatment for a range of different solid tumour types, one of which is non-small cell lung cancer.
In a Phase II double blind trial, 73 patients with locally advanced or metastatic NSCLC who had failed first or second line platinum-based chemotherapy were given 250mg or 150mg of nintedanib as a single agent twice a day.2 The median progression-free survival was 6.9 weeks, with no significant difference between the two dosage levels. One of the patients given the higher dose achieved a confirmed partial response, and the median overall survival was 22 weeks. Tumour stabilisation occurred in 46% of patients. The most common drug-related side-effects included nausea, diarrhoea, vomiting and anorexia.
A Phase III trial has recently been reported in NSCLC.3 A total of 1,314 patients with advanced or recurrent NSCLC were given 200mg nintedanib twice a day plus 75mg/m2 docetaxel, or placebo plus docetaxel.3 Progression-free survival was significantly longer than with placebo, and disease control rates were significantly improved with nintedanib, regardless of histology.
A second placebo-controlled Phase III trial, this time in combination with pemetrexed, has also been run.4 This time, 713 patients with advanced, pretreated non-squamous NSCLC were given 500mg/m2 pemetrexed along with either 200mg twice daily doses of nintedanib or placebo. After a planned futility analysis of investigator-assessed progression-free survival, enrolment was halted, with no safety issues identified. The patients were unblended and follow-up continued. Disease control and progression-free survival were both significantly improved in those given nintedanib, although there was no difference in overall survival, and the primary endpoint of progression-free survival had been met.
In a Phase II placebo-controlled trial of nintedanib as maintenance therapy after chemotherapy for relapsed ovarian cancer, 83 patients who had experienced some form of response but were at high risk of an early recurrence were given 250mg nintedanib or placebo twice a day once chemotherapy was concluded.5 After 36 weeks, the progression-free survival rate in the treated group was 16%, compared with 5% of those given placebo. Four patients continued the treatment after the trial, two for more than a year.
Other potential indications have fared less well, including glioblastoma multiforme6 and advanced colorectal cancer;7 it has also shown comparable efficacy to sunitinib in previously untreated renal cell carcinoma.8
1. F. Hilberg et al. Cancer Res. 2008, 68, 4774
2. M. Reck et al. Ann. Oncol. 2011, 22, 1374
3. M. Reck et al. J. Clin. Oncol. 2013 (suppl.), Abst LBA8011
4. N. H. Hanna et al. J. Clin. Oncol. 2013, 2013 (suppl.), Abst 8034
5. J.A. Ledermann et al. J. Clin Oncol. 2011, 29, 3798
6. Glioblastoma: A. Muhac et al. J. Neurooncol. 2013, 111, 205
7. O. Bouche et al. Anticancer Res. 2011, 31, 2271
8. T. Eisen et al. J. Clin. Oncol. 2013 (suppl.), Abst. 4506