Angiogenesis Inhibitor Tested in Mesothelioma Trial –

Nintedanib, an angiogenesis inhibitor, is being investigated as a primary-line treatment for sufferers with unresectable malignant pleural mesothelioma (MPM). Although it’s estimated that malignant mesothelioma represents lower than 1% of all cancers, it’s a deadly asbestos-related malignancy, and sufferers with MPM are typically troublesome to deal with.

The drug, which targets a number of receptors together with vascular endothelial progress issue (VEGF), fibroblast progress issue (FGF), and platelet-derived progress issue (PDGF), is being administered in mixture with pemetrexed and cisplatin in the part III, multicenter, worldwide LUME-Meso medical trial (NCT01907100).

“The current median survival of epithelioid MPM is about 15 months for most patients. Other trials have shown an improvement in overall survival, perhaps partially due to improved supportive care and secondary therapy,” stated Nicholas J. Vogelzang, MD, a medical oncologist on the Comprehensive Cancer Centers of Nevada in Las Vegas, the medical director for the Genitourinary Research Committee by way of US Oncology Research, and the vice chair of SWOG, a medical trials community.


Vogelzang, who’s the first investigator for LUME-Meso in the United States, famous that there are not any secondary therapies accredited by regulatory businesses to deal with sufferers with epithelioid MPM. Currently, the one permitted treatment routine is mixed pemetrexed and cisplatin. However, the prior MAPS research confirmed that the addition of bevacizumab (Avastin), an anti-VEGF monoclonal antibody, improved survival in sufferers with MPM,2 which prompted investigators to look into different mixture remedies with VEGF inhibitors.


Participants in the trial shall be randomized in a 1:1 ratio to obtain both oral nintedanib twice every day at 200 mg per dose mixed with intravenous pemetrexed and cisplatin, or pemetrexed and cisplatin with a placebo, adopted by upkeep remedy. Notably, sufferers may also obtain vitamin dietary supplements, together with every day oral folic acid and vitamin B12 given each eight to 9 weeks.


The LUME-Meso trial is presently enrolling sufferers who’ve epithelioid subtype MPM; sufferers with biphasic or sarcomatoid subtype might be excluded.

The FDA has accepted nintedanib underneath the commerce identify Ofev for the treatment of idiopathic pulmonary fibrosis. As a small-molecule drug, nintedanib binds competitively to the adenosine triphosphate binding pocket of the VEGF and PDGF receptors, blocking intracellular signaling wanted for the proliferation, migration, and transformation of fibroblasts which are important to the expansion of MPM. It additionally inhibits the Lck, Lyn, and Src nonreceptor tyrosine kinases. Data from the part II LUME-Meso trial demonstrated improved progression- free survival (PFS) with nintedanib remedy in sufferers with MPM. For the general inhabitants, the median PFS was 9.four months with the nintedanib mixture versus 5.7 months with pemetrexed and cisplatin alone (HR, Zero.54; 95% CI, Zero.33-Zero.87; P = .010). The median general survival (OS) was 18.Three months with nintedanib versus 14.2 months with chemotherapy alone. However, this discovering was not statistically vital (HR, Zero.77; 95% CI, Zero.46-1.29; P = .319).four The goal response fee was 57% with nintedanib and 44% with chemotherapy (odds ratio, 1.66; 95% CI, Zero.72-Three.92).

A higher profit was noticed in sufferers with epithelioid histology, the goal inhabitants of the part III research. Among these sufferers, the median OS was 20.6 months with nintedanib versus 15.2 months with chemotherapy (HR, Zero.70; 95% CI, Zero.40-1.21; P = .197). The median PFS was 9.7 months with nintedanib versus 5.7 months with chemotherapy (HR, Zero.49; 95% CI, Zero.30-Zero.82; P = .006).

In phrases of opposed occasions (AEs), nintedanib has a profile just like that of different VEGF inhibitors. In the part II research, the most typical grade ≥Three AEs have been neutropenia, elevated gamma-glutamyl transferase, elevated alanine aminotransferase, and electrolyte imbalance. Febrile neutropenia was skilled by 2.Three% of sufferers in the nintedanib arm versus none of these in the placebo group.

There are additionally some dangers of bleeding, gastrointestinal toxicities reminiscent of diarrhea and bowel perforation, and thrombosis. However, these AEs are acquainted to those that have used different VEGF inhibitors.

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