Sunitinib, sold under the brand name Sutent, is an anti-cancer medication. It is a small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) in January 2006. Sunitinib was the first cancer drug simultaneously approved for two different indications.

As of August 2021, sunitinib is available as a generic medicine in the US.

Like renal cell carcinoma, gastrointestinal stromal tumors do not generally respond to standard chemotherapy or radiation. Imatinib was the first chemotherapeutic agent proven effective for metastatic gastrointestinal stromal tumors and represented a significant development in the treatment of this rare but challenging disease. However, approximately 20% of patients do not respond to imatinib (early or primary resistance), and among those who do respond initially, 50% develop secondary imatinib resistance and disease progression within two years. Before sunitinib, patients had no therapeutic option once they became resistant to imatinib.

Sunitinib offers patients with imatinib-resistant gastrointestinal stromal tumors a new treatment option to stop further disease progression and, in some cases, even reverse it. This was shown in a large phase III clinical trial in which patients who failed imatinib therapy (due to primary or secondary resistance or intolerance) were treated in a randomized and blinded fashion with either sunitinib or placebo.

The study was unblinded early—at the first interim analysis—due to the clearly emerging benefit of sunitinib. Patients receiving a placebo were offered to switch to sunitinib at that time. In the primary endpoint of the study, the median time to tumor progression (TTP) was more than four-fold longer with sunitinib (27 weeks) compared with placebo (six weeks, P<.0001), based on an independent radiological assessment. The benefit of sunitinib remained statistically significant when stratified by many prespecified baseline variables.

Among the secondary endpoints, the difference in progression-free survival (PFS) was similar to that in TTP (24 weeks vs. six weeks, P<.0001). Seven percent of sunitinib patients had significant tumor shrinkage (objective response) compared to 0% of patients receiving placebo (P=.006). Another 58% of sunitinib patients had disease stabilization vs. 48% of patients receiving placebo. The median time to response with sunitinib was 10.4 weeks. Sunitinib reduced the relative risk of disease progression or death by 67% and the risk of death alone by 51%. The difference in survival benefit may be diluted because placebo patients crossed over to sunitinib upon disease progression, and most of these patients subsequently responded to sunitinib.

Sunitinib was relatively well tolerated. About 83% of sunitinib patients experienced a treatment-related adverse event of any severity, as did 59% of patients who received placebo. Serious adverse events were reported in 20% of sunitinib patients and 5% of placebo patients. Adverse events were generally moderate and easily managed by dose reduction, dose interruption, or other treatment. Nine percent of sunitinib patients and 8% of placebo patients discontinued therapy due to an adverse event.

Fatigue is the adverse event most commonly associated with sunitinib therapy. In this study, 34% of sunitinib patients reported any fatigue, compared with 22% for placebo. The grade 3 (severe) fatigue incidence was similar between the two groups, and no grade 4 fatigue was reported.