sunitinib
Regulatory sources consulted
Approved indications
- Adults with unresectable or metastatic gastrointestinal stromal tumor after imatinib failure due to resistance or intolerance; advanced or metastatic renal-cell carcinoma; or progressive, well-differentiated, unresectable or metastatic pancreatic neuroendocrine tumor.
- Additional FDA profile: adjuvant treatment of adults at high risk of recurrent renal-cell carcinoma after nephrectomy.
Contraindications
Absolute
- Hypersensitivity to sunitinib or excipients.
Clinical warnings
- It can cause hepatotoxicity and fatal liver failure. Monitor liver function at baseline, during each cycle, and as clinically indicated; withhold, reduce, or permanently discontinue according to severity and course. — OpenFDA, set_id 04d34bce-1296-d2b9-e063-6394a90a7018
- Monitor heart failure and LVEF, hypertension, QT interval and electrolytes, bleeding, gastrointestinal perforation, thrombotic microangiopathy, tumor lysis syndrome, thyroid dysfunction, proteinuria, and osteonecrosis of the jaw. Withhold or discontinue for severe toxicity. — CIMA/AEMPS, ficha técnica 85989
- Withhold sunitinib for at least 3 weeks before elective surgery. After major surgery, do not restart for at least 2 weeks and until adequate wound healing. — OpenFDA, set_id 04d34bce-1296-d2b9-e063-6394a90a7018
Drug interactions
- HighStrong CYP3A4 inhibitors
Mechanism: They increase sunitinib exposure.
Recommendation: Avoid when possible; if unavoidable, consider 12.5 mg reductions and monitor toxicity.
CIMA/AEMPS, ficha técnica 85989
- HighStrong CYP3A4 inducers
Mechanism: They reduce sunitinib exposure.
Recommendation: Avoid and select an alternative; if unavoidable, increase only in 12.5 mg steps with close monitoring.
CIMA/AEMPS, ficha técnica 85989
Adverse events
Common (≥1%)
decreased appetite · dysgeusia · hypertension · fatigue · diarrhea · nausea · stomatitis · vomiting · hand-foot syndrome · neutropenia · thrombocytopenia · anemia
Pregnancy and lactation
It can cause fetal harm. Verify pregnancy before starting. Women must use effective contraception during treatment and for 4 weeks afterward; men with partners who can become pregnant, during treatment and for 7 weeks afterward. Do not breastfeed during treatment or for 4 weeks afterward. Male and female fertility may be impaired.
Recent literature (PubMed)
Nivolumab plus ipilimumab (NIVO+IPI) has demonstrated superior overall survival (OS) and durable response benefits versus sunitinib (SUN) with long-term follow-up in patients with advanced renal cell carcinoma (aRCC). We report updated analyses with 8 years of median follow-up from CheckMate 214. Patients with aRCC (N = 1096) were randomized to NIVO 3 mg/kg plus IPI 1 mg/kg Q3W × four doses, followed by NIVO (3 mg/kg or 240 mg Q2W or 480 mg Q4W); or SUN (50 mg) once daily for 4 weeks on, 2 weeks off. The endpoints included OS, independent radiology review committee (IRRC)-assessed progression-free survival (PFS), and IRRC-assessed objective response rate (ORR) in intermediate/poor-risk (I/P; primary), intent-to-treat (ITT; secondary), and favorable-risk (FAV; exploratory) patients. With 8 years (99.1 months) of median follow-up, the hazard ratio [HR; 95% confidence interval (CI)] for OS with NIVO+IPI versus SUN was 0.72 (0.62-0.83) in ITT patients, 0.69 (0.59-0.81) in I/P patients, and 0.82 (0.60-1.13) in FAV patients. PFS probabilities at 90 months were 22.8% versus 10.8% (ITT), 25.4% versus 8.5% (I/P), and 12.7% versus 17.0% (FAV), respectively. ORR with NIVO+IPI versus SUN was 39.5% versus 33.0% (ITT), 42.4% versus 27.5% (I/P), and 29.6% versus 51.6% (FAV). Rates of complete response were higher with NIVO+IPI versus SUN in all International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups (ITT, 12.0% versus 3.5%; I/P, 11.8% versus 2.6%; FAV, 12.8% versus 6.5%). The median duration of response (95% CI) with NIVO+IPI versus SUN was 76.2 versus 25.1 months [59.1 months-not estimable (NE) versus 19.8-33.2 months] in ITT patients, 82.8 versus 19.8 months (54.1 months-NE versus 16.4-26.4 months) in I/P patients, and 61.5 versus 33.2 months (27.8 months-NE versus 24.8-51.4 months) in FAV patients. The incidence of treatment-related adverse events was consistent with previous reports. Exploratory post hoc analyses are reported for FAV patients, thos
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We present the final prespecified overall survival (OS) analysis of the open-label, phase III CLEAR study in treatment-naïve patients with advanced renal cell carcinoma (aRCC). With an additional follow-up of 23 months from the primary analysis, we report results from the lenvatinib plus pembrolizumab versus sunitinib comparison of CLEAR. Treatment-naïve patients with aRCC were randomly assigned to receive lenvatinib (20 mg orally once daily in 21-day cycles) plus pembrolizumab (200 mg intravenously once every 3 weeks) or sunitinib (50 mg orally once daily [4 weeks on/2 weeks off]). At this data cutoff date (July 31, 2022), the OS hazard ratio (HR) was 0.79 (95% CI, 0.63 to 0.99). The median OS (95% CI) was 53.7 months (95% CI, 48.7 to not estimable [NE]) with lenvatinib plus pembrolizumab versus 54.3 months (95% CI, 40.9 to NE) with sunitinib; 36-month OS rates (95% CI) were 66.4% (95% CI, 61.1 to 71.2) and 60.2% (95% CI, 54.6 to 65.2), respectively. The median progression-free survival (95% CI) was 23.9 months (95% CI, 20.8 to 27.7) with lenvatinib plus pembrolizumab and 9.2 months (95% CI, 6.0 to 11.0) with sunitinib (HR, 0.47 [95% CI, 0.38 to 0.57]). Objective response rate also favored the combination over sunitinib (71.3% v 36.7%; relative risk 1.94 [95% CI, 1.67 to 2.26]). Treatment-emergent adverse events occurred in >90% of patients who received either treatment. In conclusion, lenvatinib plus pembrolizumab achieved consistent, durable benefit with a manageable safety profile in treatment-naïve patients with aRCC.
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors derived from chromaffin cells, with 80-85% originating in the adrenal medulla and 15-20% from extra-adrenal chromaffin tissues (paragangliomas). Approximately 30-40% of PPGLs have a hereditary component, making them one of the most genetically predisposed tumor types. Recent advances in genetic research have classified PPGLs into three molecular clusters: pseudohypoxia-related, kinase-signaling, and WNT-signaling pathway variants. Specifically, the detection of SDHB-related tumors indicates an increased risk of metastatic disease, which may impact decisions regarding functional imaging in patients with high suspicion of metastasis and influence targeted treatment strategies. Diagnosis of PPGLs primarily relies on biochemical testing, measuring catecholamines or their metabolites in plasma or urine. However, molecular testing, functional imaging, and targeted therapies have greatly enhanced diagnostic precision and management. Personalized treatment approaches based on genetic profiling are becoming integral to the clinical management of these tumors. In South American countries like Colombia, functional imaging techniques such as positron emission tomography/computed tomography (PET/CT) with tracers like 18F-DOPA, 18F-fluorodeoxyglucose (18F-FDG), and 68Ga-DOTA-conjugated somatostatin receptor-targeting peptides (68Ga-DOTA-SST) are used to guide follow-up and treatment strategies. Radionuclide therapy with lutetium-177 DOTATATE is employed for patients showing uptake in 68Ga-DOTA-SST PET/CT scans, while access to 131-MIBG therapy remains limited due to high costs and availability. Recent clinical trials have shown promise for systemic therapies such as sunitinib and cabozantinib, offering potential new options for patients with slow or moderate progression of PPGLs. These advancements underscore the potential of personalized and targeted therapies to improve outcomes in this challenging pati
Currently, renal cell carcinoma (RCC) is the most prevalent type of kidney cancer. Targeted therapy has replaced radiation therapy and chemotherapy as the main treatment option for RCC due to the lack of significant efficacy with these conventional therapeutic regimens. Sunitinib, a drug used to treat gastrointestinal tumors and renal cell carcinoma, inhibits the tyrosine kinase activity of a number of receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), c-Kit, rearranged during transfection (RET) and fms-related receptor tyrosine kinase 3 (Flt3). Although sunitinib has been shown to be efficacious in the treatment of patients with advanced RCC, a significant number of patients have primary resistance to sunitinib or acquired drug resistance within the 6-15 months of therapy. Thus, in order to develop more efficacious and long-lasting treatment strategies for patients with advanced RCC, it will be crucial to ascertain how to overcome sunitinib resistance that is produced by various drug resistance mechanisms. In this review, we discuss: 1) molecular mechanisms of sunitinib resistance; 2) strategies to overcome sunitinib resistance and 3) potential predictive biomarkers of sunitinib resistance.
Gastrointestinal stromal tumor (GIST) is the most common malignant neoplasm of mesenchymal origin. GIST spans a wide clinical spectrum that ranges from tumors with essentially no metastatic potential to malignant and life-threatening spread diseases. Gain-of-function mutations in KIT or PDGFRA receptor tyrosine kinases are the crucial drivers of most GISTs, responsible for tumor initiation and evolution throughout the entire course of the disease. The introduction of tyrosine kinase inhibitors targeting these receptors has substantially improved the outcomes in this formerly chemoresistant cancer. As of today, five agents hold regulatory approval for the treatment of GIST: imatinib, sunitinib, regorafenib, ripretinib, and avapritinib. This, in turn, represents a success for a rare neoplasm. During the past two decades, GIST has become a paradigmatic model in cancer for multidisciplinary work, given the disease-specific particularities regarding tumor biology and tumor evolution. Herein, we review currently available evidence for the management of GIST. This clinical practice guideline has been developed by a multidisciplinary expert panel (oncologist, pathologist, surgeon, molecular biologist, radiologist, and representative of patients' advocacy groups) from the Spanish Group for Sarcoma Research, and it is conceived to provide, from a critical perspective, the standard approach for diagnosis, treatment, and follow-up.