Effectiveness of temozolomide treatment in SDHx mutant and wildtype metastatic pheochromocytoma and paraganglioma - results of a European restrospective multicentre study

Hanna Remde; Julien Hadoux; Joakim Crona; Rossella Libe; Eugenie Lim; Dalmazi Guido Di; Emanuela Arvat; Magalie Haissaguerre; Letizia Canu; Gregory Kaltsas; Peter Igaz; Henri Timmers; Svenja Noelting; Marcus Quinkler; Timo Deutschbein; Martin Fassnacht; Kroiss Matthias

doi:10.1530/endoabs.99.P89

P89

Prev Next

Section Contents Cite

Endocrine Abstracts (2024) 99 P89 | DOI: 10.1530/endoabs.99.P89

ECE2024 Poster Presentations Endocrine-Related Cancer (40 abstracts)

Effectiveness of temozolomide treatment in SDHx mutant and wildtype metastatic pheochromocytoma and paraganglioma – results of a European restrospective multicentre study

Hanna Remde ¹ , Julien Hadoux ² , Joakim Crona ³ , Rossella Libe ⁴ , Eugénie Lim ⁵ , Guido Di Dalmazi ⁶ , Emanuela Arvat ⁷ , Magalie Haissaguerre ⁸ , Letizia Canu ⁹ , Gregory Kaltsas ¹⁰ , Peter Igaz ¹¹ , Henri Timmers ¹² , Svenja Noelting ¹³ , Marcus Quinkler ¹⁴ , Timo Deutschbein ¹⁵ , Martin Fassnacht ¹ & Kroiss Matthias ¹⁶

Views

Author affiliations

¹University Hospital Würzburg, Würzburg, Germany; ²Institut Gustave Roussy, Villejuif, France; ³University of Uppsala, Uppsala, Sweden; ⁴Hôpital Cochin-Port Royal, Paris, France; ⁵St. Bartholomew’s Hospital, London, UK; ⁶IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; ⁷University of Turin, Torino, Italy; ⁸Bordeaux University, Bordeaux, France; ⁹University of Florence, Firenze, Italy; ¹⁰National and Kapodistrian University of Athens, Athens, Greece; ¹¹Semmelweis University, Budapest, Hungary; ¹²Radboud University Medical Centre, Nijmegen, Netherlands; ¹³University Hospital Zürich, Zürich, Switzerland; ¹⁴Endokrinologie in Charlottenburg, Berlin, Germany; ¹⁵Medicover MVZ Oldenburg, Oldenburg, Germany; ¹⁶LMU University Hospital, München, Germany

Background: Pheochromocytomas and paragangliomas (mPPGL) are rare neuroendocrine tumors. Therapeutic options in advanced and irresectable mPPGL are limited. Two small retrospective studies demonstrated the effectiveness of temozolomide in patients with mPPGL and suggested that patients with mutation in the succinate dehydrogenase B (SDHB) gene might benefit more than SDHB wildtype cases.

Aim: To re-evaluate safety and effectiveness of temozolomide in a larger cohort of patients with mPPGL and identify predictors of clinical response.

Methods: Data from patients with mPPGL who had received treatment with temozolomide were collected in an international retrospective setting at 15 reference centres in Europe. The objective response rate (ORR) and non-progression rate (NPR) were the primary outcome measures. The association of SDHB mutation status in and treatment response was assessed using Fisher’s exact test.

Results: Radiological outcome assessment was available for 67 (94.3%) of 71 patients included into the study at data cut-off. Best response was partial response (PR) in 18 patients and stable disease (SD) in 29. The ORR was 27% and the NPR 70%. Germline SDHB mutation was available for 56 patients including 24 (43%) patients with an SDHB mutation and 32 (57%) patients with SDHB wildtype. Objective treatment response was observed in both groups but was significantly more frequent in patients with SDHB mutation (41.6% vs 12.5%, P=0.027). Accordingly, non-progression rate was higher in patients with SDHB mutation compared to those with SDHB wildtype (83% vs 56%, P=0.044).

Conclusion: Treatment with temozolomide in mPPGL can be effective in both patients with SDHB mutation and those with SDHB wildtype. However, objective response rates and non-progression rates are higher in patients carrying an SDHB mutation.