By Lee Krug, MD, Memorial Sloan-Kettering Cancer Center
The American Society of Clinical Oncology meeting was held from June 1-4 in Chicago. This is the largest oncology meeting each year with around 30,000 attendees from all over the globe who congregate to discuss the latest research in all cancer types. I thought I would summarize a few of the presentations that were made regarding mesothelioma.
Accelerated hypofractionated hemithoracic intensity modulated radiation therapy followed by extrapleural pneumonectomy for malignant pleural mesothelioma (IMRT)
This study was presented by Dr. Marc de Perrot from Toronto, a member of our Science Advisory Board. In this approach, patients with early stage mesothelioma are treated first with high dose radiation over one week, and then, after one week of rest, patients then undergo an extrapleural pneumonectomy (EPP). If patients were found to have mediastinal lymph nodes at the time of surgery, they were planned to get chemotherapy afterward. This was a select group of patients who participated since only 18% of the patients with mesothelioma seen at the center over 4 years were enrolled on this study. Amazingly, the complications after the surgery were not more than expected, though one patient did die of an infection. Furthermore, the survival rates were quite promising; for patients with epithelioid subtype, 85% were predicted to be alive after 3 years. This is a high risk, aggressive treatment modality appropriate for only a select group of patients, and more follow up is needed. However, the excellent survival results are notable.
Randomized phase II study adding axitinib to pemetrexed-cisplatin in patients with malignant pleural mesothelioma
This was a trial conducted at a single institution in the Netherlands. The researchers were aiming to find a drug that would improve the results of standard Pemetrexed (Alimta) and cisplatin chemotherapy. In this study, another drug called axitinib was added to that chemotherapy combination. Axitinib is an oral drug that blocks the vascular endothelial growth factor receptor (VEGFR) which is responsible for the formation of new blood supply to feed the tumor, which contributes to tumor growth. Patients were placed in two groups, one-third receiving treatment with pemetrexed and cisplatin alone, and two-thirds receiving the same chemotherapy plus axitinib. Patients received three cycle of therapy, and then underwent a pleurectomy (PD). The rate of tumor shrinkage and survival times were no different with the addition of axitinib, but the trial was quite small with only 31 patients in total, so it is difficult to draw definitive conclusions.
Phase I study of cediranib in combination with cisplatin and pemetrexed in chemonaive patients with malignant pleural mesothelioma
Dr. Anne Tsao from MD Anderson (another member of our Science Advisory Board) presented the results of this study on behalf of the Southwest Oncology Group. This study had a similar goal, to find a drug that could be added to standard chemotherapy. Like axitinib, cederinib is a pill that blocks the VEGF receptor, but it also blocks another growth factor called platelet derived growth factor receptor (PDGFR). This study was designed to determine the side effects of that treatment and find the best dose. Twenty patients received the combination, and two doses of cederinib were tested. Patients received 6 rounds of chemotherapy plus cederinib, and then stayed on cederinib as a maintenance therapy after that. At the higher dose, two patients had severe diarrhea, two had debilitating fatigue, and one had confusion, so the lower dose was chosen for further study. Although the number of patients with tumor shrinkage was not impressive, the time before the cancer grew again was much longer than usual. A larger study is now ongoing in which patients are randomized, some receiving chemotherapy alone and some with chemotherapy plus cederinib.
Sensitivity of malignant mesothelioma lacking Merlin to the FAK inhibitor VS-6063: Evaluation of merlin/NF2 status in clinical samples
One of the genes that is commonly mutated in mesothelioma tumors is NF2 “(neurofibromin 2) This gene makes a protein called Merlin. Merlin sends growth signals inside the cancer cell and one of the proteins it interacts with is focal adhesion kinase (FAK). This abstract reported on experiments in the laboratory. The researchers treated mesothelioma cancer cells and also tumors in mice with a drug that blocks FAK called VS-6063. The treatment worked best in tumor cells that had NF2 mutations supporting their hypothesis. They have used this information to plan a large randomized trial with VS-6063 that is set to start this summer. Patients who have completed initial treatment with chemotherapy will be randomized to receive VS-6063 or placebo, to see if this drug delays the time before the cancer will start to grow again.