Abstract
BackgroundSarcomas are rare, heterogeneous tumors for which prognosis remains dismal in patients with advanced disease. Pazopanib, a vascular endothelial growth factor receptor inhibitor, has shown modest efficacy in patients with soft tissue sarcoma who fail cytotoxic chemotherapy. The cytotoxic agent temozolomide has also demonstrated activity in patients with advanced sarcoma.ObjectiveWe performed a retrospective case series to evaluate the feasibility of adding temozolomide to pazopanib in advanced sarcoma patients following single-agent pazopanib failure.Patients and methodsPatients with recurrent, metastatic sarcomas who had progressed on single-agent pazopanib and continued on pazopanib with the addition of temozolomide were included in this retrospective analysis to examine the tolerability and responses associated with the treatment combination.ResultsNine patients with a range of sarcoma subtypes were identified (55% female; median age, 48 years; median number of therapies prior to pazopanib, 3). All patients received combination therapy. One patient was recently started on therapy and was excluded from the analysis (n = 8 evaluable patients). Median PFS for single-agent pazopanib was 7.5 months (range 2–19). For the eight evaluable patients (63% female), best response at 4 months with pazopanib plus temozolomide was partial response (n = 1), stable disease (n = 3) and progressive disease (n = 4), with a median PFS of 3.5 months (range 0–15). Median PFS with combination treatment in patients with stable disease or response was 8 months (range 5–15). All four patients who achieved clinical benefit remain on therapy and are tolerating the combination therapy with expected but manageable side effects.ConclusionsIn heavily pretreated patients with advanced sarcoma, the addition of temozolomide to pazopanib was found to be tolerable. Future prospective trials are required to deduce whether temozolomide extends the clinical benefit of pazopanib.
Highlights
Sarcomas are a rare and heterogeneous set of diseases that have a mesenchymal origin in bone or soft tissue
Metastatic sarcomas who had progressed on single-agent pazopanib and continued on pazopanib with the addition of temozolomide were included in this retrospective analysis to examine the tolerability and responses associated with the treatment combination
The combination resulted in an impressive overall survival (OS) benefit of 26.5 months in the olaratumab with doxorubicin arm versus 14.7 months in the doxorubicin arm in their registration study [19]
Summary
Sarcomas are a rare and heterogeneous set of diseases that have a mesenchymal origin in bone or soft tissue. Soft tissue sarcomas (STS) are composed of more than 70 different subtypes and account for approximately 1% of all tumors [1,2]. The prognosis for metastatic STS is dismal [4], with a median overall survival (OS) of approximately 12 months [1,5,6] indicating a strong need for new therapeutic options. Treatment of metastatic disease remains unsatisfactory due to limited active chemotherapy options [1]. Extraskeletal myxoid chondrosarcoma and dedifferentiated chondrosarcoma are aggressive sarcomas that are typically weakly active to cytotoxic chemotherapies [14,15]; recently preliminary evidence of efficacy has been demonstrated with targeted therapies in retrospective studies [16,17]. Other sarcoma regimens combining cytotoxic and targeted therapies may be promising
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