Patients with metastatic colorectal cancer who no longer respond or tolerate other available treatments do not benefit more from nintedanib plus best supportive care (BSC) than from BSC alone, according to recent results of a Phase 3 clinical trial.
The results, which were presented at the European Society for Medical Oncology (ESMO) 2016 Congress, in Copenhagen Oct. 7-11, show that the trial reached its co-primary endpoint of progression-free survival (PFS), with nintedanib plus BSC significantly reducing the risk for disease progression by 42%, compared to BSC alone.
However, these results did not translate into a superior overall survival in patients receiving nintedanib plus BCS, failing to reach the second co-primary endpoint of the trial.
“The data confirmed nintedanib is an active compound and had a significant effect in stabilizing disease for patients with advanced colorectal cancer,” professor Eric Van Cutsem, MD, PhD, professor of internal medicine at the University of Leuven in Belgium, and lead investigator, said in a press release. “Unfortunately, this benefit did not lead to an increase in overall survival and we are currently analyzing the data to better understand this outcome,” he said.
Beohriger Ingelheim‘s nintedanib works by inhibiting a variety of signaling pathways that play important roles not only in tumor angiogenesis (the generation of new blood vessels) but also in tumor growth and metastasis, suggesting that it may be used in a variety of cancers.
Currently, it is approved to treat idiopathic pulmonary fibrosis in the U.S. and E.U., and for some cases of non-small cell lung cancer in the E.U., under the brand names Ofev and Vargatef. It also is being tested in lung, mesothelioma and colon cancer patients.
The LUME-Colon 1 trial (NCT02149108), a randomized, double-blind, placebo-controlled Phase 3 study, was designed to evaluate the safety and efficacy of nintedanib plus BSC, versus placebo plus BSC in pre-treated patients with metastatic colon cancer who failed to respond or did not tolerate other available treatments.
The trial, conducted at 150 locations worldwide, enrolled 768 participants who were randomized to receive either twice daily nintedanib (200 mg) plus BCS, or corresponding placebo plus BSC.
Results revealed that the nintedanib group had a 42% increase in PFS, showing a median PFS of 1.51 months compared to 1.38 months in the placebo group. Nonetheless, this increase in PFS did not result in improved overall survival, with those on nintedanib showing a median overall survival of 6.44 months, compared to 6.05 months in the placebo group.
Patients receiving nintedanib also exhibited more frequent Grade 3 or higher adverse events, such as liver related elevations (16% vs. 8%) and fatigue (9% vs. 6%).
“The ultimate goal of our oncology programs is to develop treatments that will change clinical practice to benefit the lives of patients and their families,” said Mehdi Shahidi, MD, vice president and global head of medicine, oncology with Boehringer Ingelheim. “While the outcome of the LUME-Colon 1 trial is not what we had hoped for, we continue to learn and evolve our research strategy with every study result from our development program,” he said.