A phase 2 trial of sunitinib in patients with progressive paraganglioma or pheochromocytoma: the SNIPP trial

Br J Cancer. 2019 Jun;120(12):1113-1119. doi: 10.1038/s41416-019-0474-x. Epub 2019 May 20.

Abstract

Background: Pheochromocytoma (PCC) and paraganglioma (PGL) are uncommon neoplasms with high morbidity in advanced stages. Effective systemic treatments are limited.

Methods: A multisite phase 2 trial evaluated sunitinib in patients with progressive PCC/PGL. Patients received 50 mg orally for 4-6 weeks.

Results: Between May 2009 and May 2016, 25 patients were enroled. The median age was 50 years and 56% were male. Three patients (12%) received prior chemotherapy and 16 (64%) prior surgery. The DCR was 83% (95% CI: 61-95%) and median PFS 13.4 (95% CI: 5.3-24.6) months. Of 23 evaluable patients, 3 (13%) with germline mutations (SDHA, SDHB, RET) achieved a PR. The patient with mutated RET and MEN2A remains on treatment after 64 cycles. The median time on treatment was 12.4 (1-88.0) months. Grade 3 or 4 toxicities were as expected and manageable; fatigue (16%) and thrombocytopenia (16%) were most common. One patient with grade 3 hypertension and 2 with grade 3 cardiac events discontinued treatment.

Conclusion: Although the primary endpoint of disease control was met, the overall response rate of sunitinib was low in unselected patients with progressive PCC/PGL. Patients with germline variants in RET or in the subunits of SDH may derive greatest benefit.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Gland Neoplasms / drug therapy*
  • Adrenal Gland Neoplasms / pathology
  • Antineoplastic Agents / therapeutic use
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Paraganglioma / drug therapy*
  • Paraganglioma / pathology
  • Pheochromocytoma / drug therapy*
  • Pheochromocytoma / pathology
  • Protein Kinase Inhibitors / therapeutic use
  • Sunitinib / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Sunitinib