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A phase II study of intermittent sunitinib malate as second-line therapy in progressive malignant pleural
Anna K Nowak1, Michael J Millward, Jenette Creaney
1Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia. anowak@meddent.uwa.edu.au
Introduction:
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.
Insights
Sunitinib showed activity in some patients with advanced malignant pleural mesothelioma (MPM) after chemotherapy. Further research into different schedules and biomarkers is recommended for this difficult-to-treat cancer.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Malignant pleural mesothelioma (MPM) lacks established second-line therapies after chemotherapy.
- Sunitinib malate, a multitargeted tyrosine kinase inhibitor, targets pathways implicated in mesothelioma.
- This study investigated sunitinib's efficacy and biomarkers in pretreated MPM.
Purpose of the Study:
- To assess the objective radiological response to sunitinib in patients with advanced MPM.
- To evaluate correlative biomarkers, including serum markers and imaging, for treatment response.
- To determine the safety and tolerability of sunitinib in this patient population.
Main Methods:
- Phase II clinical trial enrolling 53 patients with progressive MPM post-chemotherapy.
- Sunitinib administered orally at 50 mg daily on a 28/42-day schedule.
- Objective radiological response was the primary endpoint; fluorodeoxyglucose positron emission tomography (FDG-PET) assessed response in patients without prior pleurodesis.
Main Results:
- 12% of patients achieved a confirmed partial radiological response; 65% had stable disease.
- Median overall survival was 6.1 months; median time to progression was 3.5 months.
- Fatigue was the most common toxicity; correlative biomarkers did not predict treatment response.
Conclusions:
- Sunitinib demonstrates activity in a subset of pretreated MPM patients.
- Further investigation into alternative dosing schedules and novel biomarkers is warranted.
- Sunitinib represents a potential option for patients with limited therapeutic choices.
