sunitinib

Overview

Sunitinib is an oral multi-targeted receptor tyrosine kinase inhibitor (TKI) that targets KIT, PDGFRA, VEGFR2, FLT3, CSF1R, and RET. It is FDA-approved as second-line therapy for gastrointestinal stromal tumors (GIST) following imatinib failure or intolerance, and as first-line therapy for advanced renal cell carcinoma and pancreatic neuroendocrine tumors. In GIST, sunitinib is particularly relevant for tumors with KIT/PDGFRA-wildtype histology (e.g., SDH-deficient or NF1-related GISTs) that do not respond to imatinib.

Evidence in the corpus

  • Cited as a therapeutic option relevant to GIST patients harboring germline P/LP variants in SDH-complex genes (SDHA/SDHB/SDHC) or NF1, whose tumors are KIT/PDGFRA-wildtype and respond poorly to imatinib; sunitinib is referenced in the context of germline-guided therapy selection in 103 GIST patients with matched tumor-germline MSK-IMPACT sequencing PMID:36593350
  • Used as the comparator arm in IMmotion151 and JAVELIN Renal 101 trials; TKI-preferred ccRCC patients trended toward longer PFS with sunitinib (median 14 months) vs. bevacizumab+atezolizumab (median 10 months, p=0.06) in the HiTME decision-tree analysis PMID:22138691
  • NCI-60 CellMiner pharmacogenomics study examined genomic determinants of sunitinib sensitivity across cancer cell lines including colon PMID:22802077
  • High PDGFRA/PDGFRB expression in metastatic PanNEN patients (PN2, PN10) guided sunitinib recommendation in the POG NEN WGTA cohort (n=28) PMID:24326773
  • One of 10 ccRCC tumors received 14–16 weeks of preoperative sunitinib; authors argue this cytostatic exposure did not collapse intratumor heterogeneity, though a treatment-naive baseline at this scale is unavailable PMID:24487277
  • Failed as frontline HCC therapy vs sorafenib (phase III): median OS 8.0–8.8 vs 9.9–10.0 months for sorafenib (HR 1.12–1.15); demonstrated inferior efficacy in first-line setting PMID:24798001
  • Multi-kinase inhibitor (KIT/PDGFRA/VEGFR); proposed as therapeutic candidate for KIT-mutant GCT alongside imatinib in Appendix Table A2 of the cisplatin-resistance biomarker study PMID:27646943

Resistance mechanisms

  • Not reported in corpus.

Cancer types (linked)

  • GIST — second-line after imatinib failure; particularly for SDH-deficient and NF1-related GISTs

Sources

  • PMID:36593350 — Mandelker et al. 2023, npj Precision Oncology; germline testing in GIST; sunitinib referenced for imatinib-resistant subtypes.

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This page was processed by crosslinker on 2026-05-09. - PMID:24326773

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