Real-word experience of pazopanib and sorafenib in patients with desmoid tumors: A CanSaRCC multi-center study

Eur J Cancer. 2024 Jul:205:114119. doi: 10.1016/j.ejca.2024.114119. Epub 2024 May 14.

Abstract

Background: Sorafenib and pazopanib, two tyrosine kinase inhibitors (TKI), are widely used in patients with progressive symptomatic desmoid tumors (DT). Limited real-word data is available on long-term outcomes of patients who progressed on, stopped, or continued TKIs.

Methods: Patients diagnosed with DTs and treated with sorafenib or pazopanib between 2011 and 2022 at 11 institutions were reviewed. Patient history, response to therapy and toxicity were recorded. Statistical analyses utilized Kaplan-Meier and log-rank tests.

Results: 142 patients with DT treated with sorafenib (n = 126, 88.7 %) or pazopanib (n = 16, 11.3 %) were analyzed. The median treatment duration was 10.8 months (range: 0.07- 73.9). The overall response rate and the disease control rate were 26.0 % and 95.1 %, respectively. The median tumor shrinkage was - 8.5 % (range -100.0 %- +72.5 %). Among responders, the median time to an objective response was 15.2 months (range: 1.1 to 33.1). The 1-year and 2-year progression-free survival rates were 82 % and 80 %. Dose reductions were necessary in 34 (23.9 %) patients. Grade 3 or higher adverse events were reported in 36 (25.4 %) patients. On the last follow-up, 55 (38.7 %) patients continued treatment. Treatment discontinuation (n = 85, 59.9 %) was mainly for toxicity (n = 35, 45.9 %) or radiological or clinical progression (n = 30, 35.3 %). For the entire cohort, 36 (25.4 %) patients required subsequent treatment. In the 32 responders, only 1 (3.1 %) patient required a subsequent treatment. In patients who discontinued TKI, 25 (44.6 %) with stable disease received subsequent treatment compared to 0 (0.0 %) of responders.

Conclusion: This retrospective study represents the largest cohort of DT patients treated with sorafenib or pazopanib to date. Discontinuation of treatment in responders is safe. The optimal treatment duration in patients with stable disease remains to be defined.

Keywords: Desmoid tumor; Pazopanib; Sorafenib; Targeted therapy; Treatment discontinuation.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Female
  • Fibromatosis, Aggressive* / drug therapy
  • Fibromatosis, Aggressive* / pathology
  • Humans
  • Indazoles*
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines* / adverse effects
  • Pyrimidines* / therapeutic use
  • Retrospective Studies
  • Sorafenib* / adverse effects
  • Sorafenib* / therapeutic use
  • Sulfonamides* / adverse effects
  • Sulfonamides* / therapeutic use
  • Treatment Outcome
  • Young Adult

Substances

  • pazopanib
  • Indazoles
  • Sorafenib
  • Sulfonamides
  • Pyrimidines
  • Protein Kinase Inhibitors