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Malignant pheochromocytomas/paragangliomas are rare tumors for which clinical outcomes remain poorly defined and therapeutic options are limited. Approximately 27% carry pathogenic germline succinate dehydrogenase (SDHx) mutations; the presence of such mutations has been correlated with response to temozolomide. We aimed to investigate the association between SDHx and response to temozolomide. We retrospectively identified patients with malignant pheochromocytomas/paragangliomas treated with temozolomide - based chemotherapy at Dana-Farber Cancer Institute between 2003-2020. Correlation between response by RECIST 1.1 and PERCIST and presence of SDHx mutations in the germline and tumor was evaluated. 19 patients received temozolomide. 17 underwent germline assessment: nine (53%) carried a pathogenic SDHx germline mutation. 15 patients were evaluable for response by RECIST 1.1: 6 (40%) partial response, 4 (27%) stable disease, and 5 (33%) progressive disease. Overall median progression free survival was 2.2 years. Three-year overall survival was 58%. Median progression free survival was 1.3 years and 5.5 years for carriers and non-carries, respectively and overall survival was 1.5 years and not estimable for carriers and non-carriers, respectively. Response by PERCIST criteria in 9 patients correlated with the RECIST 1.1 assessment. Our series represents one of the largest analyses of patients with malignant pheochromocytomas/paragangliomas treated with temozolomide who have available germline data. The incidence of pathogenic germline SDHx mutations was similar to what has been previously published, though our analysis suggests that there may be limited association between response to temozolomide and pathogenic germline SDHx mutations.

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