Journal of Thoracic Oncology 2017 June 6 [Epub ahead of print] [Link]
Tsao AS, Moon J, Wistuba II, Vogelzang NJ, Kalemkerian GP, Redman MW, Gandara DR, Kelly K
In malignant pleural mesothelioma (MPM), targeting angiogenesis, with cediranib, a vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor (PDGFR) inhibitor, may have therapeutic potential.
S0905 phase I combined cediranib (2 dose cohorts 30 mg and 20 mg daily) with cisplatin-pemetrexed for 6 cycles followed by maintenance cediranib in unresectable chemo-naïve MPM patients of any histologic subtype. The primary endpoint established the MTD in combination with cisplatin-pemetrexed in a dose de-escalation schema.
A total of 20 patients (7 to cohort 30 mg, 13 to cohort 20 mg) were enrolled. In the cediranib 30 mg dose cohort, 2 of the initial 6 patients reported DLTs and the dose was deemed too toxic to continue. In the next cohort, 2 patients experienced DLTs and thus the MTD was established as cediranib at 20 mg. During the 6 cycles of cisplatin-pemetrexed-cediranib 20 mg, there were grade 3 toxicities (neutropenia, gastrointestinal) and grade 4 thrombocytopenia. No patients had any significant episodes of bleeding. By RECIST (n=17), the median PFS was 12.8 months (95% CI: 6.9 – 17.2); by modified RECIST (n=19), the median PFS was 8.6 months (95% CI: 6.1-10.9). For all patients, the disease control rate at 6 weeks was 90% and median OS was 16.2 months (95% CI: 10.5 – 28.7).
Cediranib combined with cisplatin-pemetrexed has a reasonable toxicity profile and preliminary promising efficacy. The phase II S0905 trial will evaluate the efficacy of the triplet regimen compared to the current standard of care cisplatin-pemetrexed.