A phase II study of intermittent sunitinib malate as second-line therapy in progressive malignant pleural mesothelioma.
BACKGROUND
There is no accepted second-line therapy for patients with advanced malignant pleural mesothelioma (MPM), whose disease has progressed after first-line chemotherapy. The multitargeted tyrosine kinase inhibitor sunitinib malate targets several pathways overexpressed in mesothelioma. This phase II study assessed objective response to sunitinib and correlative biomarkers in patients with progressive pretreated MPM.


METHODS
Eligible patients had confirmed MPM, radiological progression after chemotherapy, Eastern Cooperative Oncology Group performance status 0 to 1, and measurable disease. Patients received oral sunitinib 50 mg daily for 28 of every 42 days. The primary endpoint was objective radiological response. Patients without prior pleurodesis had fluorodeoxyglucose positron emission tomographic response assessed by total glycolytic volume criteria. Correlative biomarkers included serum mesothelin, vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8, sVEGFR-2, sVEGFR-3, and s-kit.


RESULTS
Fifty-three patients received sunitinib between July 2006 and December 2009; 51 were assessable for response. Patients received a median of two cycles (range, 1-12); 40% required dose reduction. Fatigue was the most prominent toxicity. Six patients (12%) had a confirmed radiological partial response, 34 (65%) had stable disease, and 11 (22%) had progressive disease as best response. Six of 20 patients had a decrease in fluorodeoxyglucose positron emission tomographic total glycolytic volume of 15% or more. Median overall survival was 6.1 months, and median time to progression was 3.5 months. Correlative biomarkers did not predict treatment response.


CONCLUSIONS
Sunitinib has activity in a subset of patients with pretreated MPM. Consideration should be given to different treatment schedules and examination of other biomarkers for further study of sunitinib in MPM.
Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia. anowak@meddent.uwa.edu.au
Anna K
AK
Nowak
Michael J
MJ
Millward
Jenette
J
Creaney
Roslyn J
RJ
Francis
Ian M
IM
Dick
Arman
A
Hasani
Agatha
A
van der Schaaf
Amanda
A
Segal
Arthur W
AW
Musk
Michael J
MJ
Byrne
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D015996:Survival Rate
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib