It is official – the VEGF inhibitor Ofev is out of the running as a treatment for pleural mesothelioma.
Hopes had been high for this drug after initial results showed a survival advantage. For the last two years, Ofev (nintedanib) was the subject of a large, international clinical trial.
But now the leaders of that trial have published their Phase III trial results in The Lancet: Respiratory Medicine. They show that Ofev did not extend survival and is not an effective treatment for pleural mesothelioma.
Why Hopes Were High for Ofev
Ofev is an oral medication that stops cancer cells from producing a protein called VEGF. VEGF promotes the growth of blood vessels that help mesothelioma tumors grow.
VEGF may also play a role in suppressing the immune system’s ability to fight off mesothelioma. Patients with high VEGF levels tend to have shorter survival.
The hope was that giving Ofev along with standard chemotherapy treatment for pleural mesothelioma would help those drugs work better and improve survival.
In the Phase II part of the LUME-Meso trial, that seemed to be the case. Researchers reported a survival gain of more than 5 months among the Ofev-treated mesothelioma patients. These patients also had an average of four months where their cancer stopped growing.
Ofev did not appear to cause serious side effects in most patients.
Phase III Shows No Improvement in Treatment for Pleural Mesothelioma
After the promising Phase II results, researchers moved forward with the third part of the Ofev trial.
One hundred and twenty clinics and hospitals in 27 countries participated in the trial. It included newly-diagnosed patients who had not yet had any treatment for pleural mesothelioma.
Between April 2016 and January 2018, 458 mesothelioma patients had up to six cycles of chemotherapy with pemetrexed (Alimta) and cisplatin. Half of the patients received nintedanib along with chemotherapy and half received a placebo.
After six cycles, patients whose cancer had not progressed got Ofev or a placebo as a maintenance therapy.
“After 250 events, progression-free survival was not different between the nintedanib group and the placebo group,” writes lead investigator Dr. Giorgio Scagliotti of the University of Turin.
Both groups of patients lived about 7 months, regardless of which treatment for pleural mesothelioma they had. They even had about the same number of complications or “adverse events”.
Since the Phase III trial did not support the Phase II findings, the researchers do not recommend Ofev as a treatment for pleural mesothelioma.
Other VEGF Inhibitors May Still Help
The results do not mean that other VEGF inhibitors might not extend mesothelioma survival.
The VEGF inhibitor bevacizumab (Avastin), along with Alimta and cisplatin, is now a standard first-line treatment for pleural mesothelioma in France. In the US, National Comprehensive Cancer Network guidelines have also included this three-drug combination as an option for mesothelioma treatment since 2016.
Sorafenib (Nexavar) and cediranib (Recentin) may also impact the effectiveness of mesothelioma chemotherapy.
Scagliotti, GV, et al, “Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial”, May 15, 2019, Lancet Respiratory Medicine, Epub ahead of print, https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(19)30139-0/fulltext