A phase II trial of dovitinib in previously-treated advanced pleural mesothelioma: The Ontario Clinical Oncology Group. (February 2017)

• Record Type: Journal Article
• Authors: Laurie, Scott A.; Hao, Desiree; Leighl, Natasha B.; Goffin, John; Khomani, Abderrahim; Gupta, Ashish; Addison, Christina L.; Bane, Anita; Seely, Jean; Filion, Marc L.; Pond, Gregory R.; Levine, Mark N.
• Is Part Of: Lung cancer. Volume 104(2017)
• Page Start: 65
• Page End: 69
• Publication Date: 2017-02
• Subjects: Mesothelioma -- Angiogenesis -- Fibroblast growth factor receptor -- Phase II; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2016.12.004
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Treatment of MPM at progression after platinum-antifolate is an unmet need. The role of the FGFR pathway in MPM has not been fully elucidated. Dovitinib is a multi-targeted tyrosine kinase inhibitor of VEGFR and FGFR. In pre-treated MPM dovitinib had no significant activity and was poorly tolerated. It is unclear if at the doses administered FGFR was effectively inhibited. Abstract: Objectives: Following failure of a platinum-antifolate combination regimen, there is no standard therapy for advanced malignant pleural mesothelioma (MPM). The fibroblast growth factor receptor (FGFR) signaling pathways may be a relevant target in MPM. Dovitinib inhibits multiple tyrosine receptor kinases, predominantly the vascular endothelial growth factor receptors (VEGFR), but also FGFRs, and could be active in MPM. Methods: This open-label multicentre phase II trial [NCT01769547] enrolled fit, consenting adult patients with advanced MPM who had previously received platinum-antifolate combination chemotherapy and up to one additional line of systemic therapy. Dovitinib was administered orally at 500 mg/day for 5 days on, 2 days off, in 28-day cycles. Response was assessed every 2 cycles using RECIST 1.1 criteria modified for MPM. Correlative studies included FGFR-1 amplification on archival tumour and serum samples for circulating angiogenesis factors. The primary end-point was the proportion of patients progression-free at 3 months (PF3) using a two-stage design. Results: 12 patients (10 males, median age 67) were enrolled. The median number of cycles administered was 2.5 (range 1–8). One unconfirmed partial response was observed. PF3 was 50% (95% confidence interval 28.4% to 88.0%); although the criterion for proceeding to stage II accrual was met, the trial was halted due to a combination of minimal activity with several early progression events and poor tolerability in this patient population. One of 12 tumour specimens had low amplification of FGFR-1. Conclusions: Dovitinib has minimal activity in previously-treated MPM. The role of the FGFR pathway in MPM remains unclear.