In the quest to develop new, more effective first-line treatments for malignant pleural mesothelioma, it now looks like Ofev (nintedanib) is out of the running.
Phase III results of the LUME-Meso mesothelioma trial are in and they contain some disappointing news for mesothelioma patients and for the drug’s developer, Boehringer Ingelheim.
The news is especially disappointing since the results of the Phase II portion of the trial, released last year, looked promising. At that time, researchers reported a survival gain of more than 5 months among the Ofev-treated mesothelioma patients and progression-free survival of four months.
But further research did not support those results, as investigators announced to the world’s lung cancer experts at the IASLC 19th World Lung Cancer Conference last month.
“We are disappointed that the encouraging efficacy signal observed for nintedanib in Phase II was not confirmed in a larger Phase III trial, as there still remains a big gap in treatment options for patients with malignant pleural mesothelioma,” said Dr. Victoria Zazulina, Global Head of Solid Tumor Oncology at Boehringer Ingelheim.
Zazulina said results from the failed trial could still help guide future mesothelioma research.
Why There Were High Hopes for Ofev in Mesothelioma Treatment
Nintedanib is an oral drug designed to block a protein called VEGF which stimulates the formation of the blood vessels that mesothelioma tumors need to live and grow.
Evidence suggests that VEGF may also play a role in suppressing the immune system’s ability to fight cancers like mesothelioma and research has found that mesothelioma patients who have higher serum levels of of the protein have a lower chance of survival.
LUME-Meso was a phase II/III randomized double-blind trial aimed at assessing the safety and effectiveness of nintedanib along with pemetrexed (Alimta) and cisplatin as a first-line mesothelioma treatment.
It was thought that nintedanib would counter the effects of VEGF in mesothelioma patients and compound the effects of their chemotherapy.
Other VEGF Inhibitors Still in the Running for Mesothelioma
Although Ofev failed to meet expectations for mesothelioma researchers, a number of other VEGF-inhibitors are still being studied and, in some cases, used in mesothelioma treatment.
The VEGF inhibitor bevacizumab (Avastin) in combination with pemetrexed/cisplatin chemotherapy has been adopted as the standard of care for first-line mesothelioma treatment in France.
The addition of Avastin to standard mesothelioma care came after the 2016 French-led mesothelioma avastin cisplatin pemetrexed study (MAPS) showed that the VEGF inhibitor improved mesothelioma survival by 23 percent.
In the US, the National Comprehensive Cancer Network guidelines have also included this three-drug combination as an option for standard first-line mesothelioma treatment since 2016.
VEGF blockers sorafenib (Nexavar) and cediranib (Recentin) have also been shown to have an impact on the effectiveness of mesothelioma chemotherapy.
“Results of LUME-Meso trial in malignant pleural mesothelioma presented at the 19th World Conference on Lung Cancer (WCLC 2018)”, September 25, 2018, Boehringer Ingelheim new release, https://www.boehringer-ingelheim.us/press-release/results-lume-meso-trial-malignant-pleural-mesothelioma-presented-19th-world-conference