Background
Phase III double-blind RCT. 312 patients with imatinib-resistant or imatinib-intolerant advanced GIST. Established second-line therapy after imatinib failure.
Interventions and follow up
Arm A: sunitinib 50mg daily, 4 weeks on / 2 weeks off (n=207)
Arm B: placebo (n=105)
Primary endpoint: Time to tumor progression (TTP)
Arm B: placebo (n=105)
Primary endpoint: Time to tumor progression (TTP)
Results
mTTP: 27.3wk vs 6.4wk, HR 0.33, P<.0001 favoring sunitinib
OS: not reached, HR 0.49, 95%CI 0.29-0.83, P=.007 (placebo crossover permitted)
Best response: PR 7% vs 0%; SD 58% vs 48%; PD 19% vs 37%
OS: not reached, HR 0.49, 95%CI 0.29-0.83, P=.007 (placebo crossover permitted)
Best response: PR 7% vs 0%; SD 58% vs 48%; PD 19% vs 37%
Adverse events
Constitutional / GI (>20%): fatigue, diarrhea, nausea
Dermatologic: skin discoloration, hand-foot syndrome
Cardiovascular / endocrine: hypertension and hypothyroidism (note: sunitinib is metabolized by CYP3A4)
Dermatologic: skin discoloration, hand-foot syndrome
Cardiovascular / endocrine: hypertension and hypothyroidism (note: sunitinib is metabolized by CYP3A4)
Conclusions
Sunitinib significantly prolonged TTP and overall survival versus placebo in imatinib-resistant/intolerant GIST, establishing it as standard second-line therapy.
Key Limitations
Trial unblinded early at interim analysis with placebo crossover, confounding mature OS estimates; objective response rate was low (mostly disease stabilization); intermittent 4/2 schedule toxicity prompts frequent use of continuous lower-dose dosing in practice, not tested here.
Clinical Context
FDA approved sunitinib for imatinib-resistant/intolerant GIST in 2006. It remains the standard second-line TKI per ESMO and ASCO, followed by regorafenib (third line) and ripretinib (fourth line). Continuous daily sunitinib 37.5mg is a commonly used alternative schedule.