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VEGF-Inhibitor Avastin Shows Promise for Treating Malignant Pleural Mesothelioma

Malignant Pleural Mesothelioma (MPM) accounts for the vast majority of cases of mesothelioma. This rare, but aggressive disease is a type of cancer that affects the mesothelial surface of the pleural cavity (the membranes around the lungs). The largest number of reported deaths from mesothelioma today occur in the U.S. and the prevalence of the disease is higher in males. Though the fact that mesothelioma primarily affects males cannot be changed, researchers say that the number of deaths from the disease can with the right combination of drugs and targeted-therapies.

Currently, the mainstay of MPM management is surgery, radiation, and chemotherapy, with chemotherapy being the primary treatment method for the majority of patients. However, researchers have found that adding certain targeted-therapies to systemic chemotherapy drugs such as cisplatin (trade name Platinol) and pemetrexed (Alimta) could greatly enhance the effectiveness of chemotherapy treatment, thus improving overall survival (OS). One such targeted-therapy is a vascular endothelial growth factor (VEGF) inhibitor called bevacizumab, trade name Avastin.

According to Pavel Levin, MD, PhD, and Jonathan Dowell, MD, of the University of Texas Southwestern Medical Center, and authors of Spotlight on bevacizumab and its’ potential in the treatment of malignant pleural mesothelioma: the evidence to date, “vascular endothelial growth factor (VEGF) and its receptor have been recognized as important players in the biology of this disease. Bevacizumab is a monoclonal antibody that binds VEGF and blocks its interaction with the VEGF receptor. Recent studies have shown benefit with the addition of bevacizumab to the combination of cisplatin and pemetrexed in MPM. This combination is now included in the National Comprehensive Cancer Network guidelines (with a category 2A recommendation) as a possible first-line treatment for unresectable MPM in appropriately selected patients.”

In addition, writes Drs. Levin and Dowell, “immunotherapy agents (including programmed cell death 1 [PD-1], programmed death ligand 1 [PD-L1], and cytotoxic T lymphocyte-associated 4 [CTLA-4] inhibitors) are currently being investigated in MPM and preliminary studies show encouraging activity with these drugs.” Developing evidence suggests that VEGF may suppress T-cell-mediated immune response as well, and therefore, “anti-VEGF therapies may augment the effect of immunotherapy in cancer.” This, says the team, “provides a strong preclinical rationale for future trials targeting VEGF in combination with immunotherapy in MPM.” In fact, a trial of pembrolizumab and nintedanib (PEMBIB) is currently recruiting patients across different malignancies, including MPM.

Currently, Avastin is FDA approved to treat certain types of colon cancer, ovarian cancer, advanced cervical cancer, kidney cancer, brain cancer, and advanced nonsquamous non-small cell lung cancer (NSCLC). Drs. Levin and Dowell expect to see further clinical studies with bevacizumab-based chemotherapy regimens in combination with immunotherapy in patients with MPM.

 

Sources

Avastin® (bevacizumab) | Official Patient & Caregiver Website. Genentech USA, 2017. Web. 21 June 2017.

Levin, Pavel A., and Jonathan E. Dowell. "Spotlight on Bevacizumab and Its’ Potential in the Treatment of Malignant Pleural Mesothelioma: The Evidence to Date." OncoTargets and Therapy. Dove Medical Press, 07 Apr. 2017. Web. 21 June 2017.

"Trial Of Pembrolizumab And Nintedanib (PEMBIB)." ClinicalTrials.gov. U.S. National Library of Medicine (NLM), U.S. National Institutes of Health (NIH), U.S. Department of Health and Human Services (HHS), 02 Aug. 2016. Web. 21 June 2017.