Aaron S. Mansfield, MD
The discussant of the STELLAR trial abstract, Aaron S. Mansfield, MD, a translational scientist at the Mayo Clinic in Rochester, called the survival outcomes “very promising” for a trial that included a relatively large population of patients with the more aggressive sarcomatoid variant of mesothelioma. However, he stressed that nonrandomized phase II trials do not definitively establish benefit. Dr. Mansfield also cited more recent clinical data than those from Vogelzang et al,1 which make for a more appropriate historical control.
Results in Context
“We should consider the results of Dr. Grosso and colleagues in context of the randomized phase III MAPS trial,2 in which the addition of bevacizumab to pemetrexed plus cisplatin significantly improved median overall survival in malignant pleural mesothelioma vs pemetrexed plus cisplatin alone. Patients in the control arm had a median survival of 16 months, which was 4 months better than in the Vogelzang group,” said Dr. Mansfield. Despite the median overall survival benefit shown with the addition of bevacizumab to pemetrexed plus cisplatin (18.8 months), he added, the U.S. Food and Drug Administration has not approved this combination for mesothelioma.
Despite the limitations associated with phase II data, Dr. Mansfield concluded that these results suggest that the use of tumor-treating fields in combination with chemotherapy may be synergistic and thus appropriate for patients with mesothelioma.
“Although there were a few cases of grade 3 dermatitis, the toxicity did not seem to be significantly worse,” he said. “However, it might be helpful to look at the duration of the grade 1 and 2 dermatitis events and whether that affects compliance with the use of the alternating electrical currents.”
Adding Checkpoint Inhibitors to the Mix
According to Dr. Mansfield, checkpoint inhibitors are also starting to demonstrate impressive outcomes in this patient population. In one open-label phase II study, presented at the 2018 World Conference on Lung Cancer,3 the addition of the programmed cell death ligand 1 inhibitor durvalumab to cisplatin and pemetrexed led to a progression-free survival of 6.2 months with a 48% response rate—nearly double the rate expected with chemotherapy alone.
In addition, the combination of ipilimumab and nivolumab is being studied against the cytotoxic chemotherapy standard in the first-line setting as well, with data expected in 2020. Finally, the addition of pembrolizumab to chemotherapy is also being studied in advanced malignant pleural mesothelioma. “We’re hopeful that these combinations may improve outcomes like we’ve seen in non–small cell lung cancer,” said Dr. Mansfield. ■
DISCLOSURE: Dr. Mansfield has served as a consultant/advisor (honoraria to institution) with AbbVie, TrovaGene, Bristol-Myers Squibb, and Genentech; and has received institutional research funding from Novartis.
REFERENCES
1. Vogelzang NJ, Rusthoven JJ, Symanowski, J, et al: Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 21:2636-2644, 2003.
2. Zalcman G, Mazieres J, Margery J, et al: Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): A randomised, controlled, open-label, phase 3 trial. Lancet 387:1405-1414, 2016.
3. Nowak A, Kok P, Lesterhuis W, et al: OA08.02 DREAM: A phase 2 trial of durvalumab with first line chemotherapy in mesothelioma: Final result. J Thorac Oncol 13:S338-S339, 2018.
