| Author |
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. |
| Description |
Author Affiliation: Laurie SA ( The Ottawa Hospital Cancer Centre, 501 Smyth Road Ottawa, ON, Canada. Electronic address: slaurie@toh.on.ca.); Hao D ( Tom Baker Cancer Centre, 1331 29 Street NW, Calgary, AB, Canada. Electronic address: desiree.hao@albertahealthservices.ca.); Leighl NB ( Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON, Canada. Electronic address: nleighl@uhn.ca.); Goffin J ( Juravinski Cancer Centre, 699 Concession St, Hamilton, ON, Canada. Electronic address: goffinj@hhsc.ca.); Khomani A ( The Cancer Centre of NorthEastern Ontario, 41 Ramsey Lake Road, Sudbury, ON, Canada. Electronic address: xopowbiu@gmail.com.); Gupta A ( The Ottawa Hospital Cancer Centre, 501 Smyth Road Ottawa, ON, Canada. Electronic address: ashgupta@toh.ca.); Addison CL ( Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON, Canada. Electronic address: caddison@ohri.ca.); Bane A ( Department of Pathology and Molecular Medicine and Department of Oncology, McMaster University, 699 Concession St, Hamilton, ON, Canada. Electronic address: bane@hhsc.ca.); Seely J ( The Ottawa Hospital Cancer Centre, 501 Smyth Road Ottawa, ON, Canada. Electronic address: jeseely@toh.ca.); Filion ML ( Ontario Clinical Oncology Group, McMaster University, 711 Concession St, Hamilton, ON, Canada. Electronic address: filion@mcmaster.ca.); Pond GR ( Ontario Clinical Oncology Group, McMaster University, 711 Concession St, Hamilton, ON, Canada. Electronic address: gpond@mcmaster.ca.); Levine MN ( Ontario Clinical Oncology Group, McMaster University, 711 Concession St, Hamilton, ON, Canada. Electronic address: mlevine@mcmaster.ca.) |
| 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 500mg/day for 5days on, 2days 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. |
