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Aim: Examine outcomes in sunitinib-treated patients by International Metastatic RCC Database Consortium (IMDC) or Memorial Sloan-Kettering Cancer Center (MSKCC) risk factors. Patients & methods: Patients enrolled in STAR-TOR registry (n = 327). End points included overall survival, progression-free survival and objective response rate. Results: Overall survival was similar for IMDC 0 versus 1 (p = 0.238) or 2 versus ≥3 (p = 0.156), but different for MSKCC (0 vs 1, p = 0.037; 2 vs ≥3, p = 0.001). Progression-free survival was similar for IMDC 2 versus 3 (p = 0.306), but different for MSKCC (p = 0.009). Objective response rate was different for IMDC 1 (41.9%) and 2 (29.5%) and similar for MSKCC 1 (34.4%) and 2 (31.0%). Conclusion: Outcome data varied according to IMDC or MSKCC. MSKCC model accurately stratify patients into risk groups. Clinical trial registration: NCT00700258 (ClinicalTrials.gov).

The aim of this study was to evaluate the association between axitinib, sunitinib and temsirolimus toxicities and patient survival in metastatic renal cell cancer patients. Overall survival (OS) and progression-free survival (PFS) of metastatic renal cell cancer patients from the prospective multicenter STAR-TOR study were assessed using multivariable Cox models. A total of 1195 patients were included (n = 149 axitinib; n = 546 sunitinib; n = 500 temsirolimus). The following toxicities significantly predicted outcomes: hand-foot skin reaction (hazard ratio [HR] = 0.29) for PFS with axitinib; stomatitis (HR = 0.62) and pneumonitis (HR = 0.23) for PFS with temsirolimus; stomatitis (HR = 0.52) and thrombocytopenia (HR = 0.6) for OS with temsirolimus; fatigue (HR = 0.71) for PFS with sunitinib; hand-foot skin reaction (HR = 0.56) and fatigue (HR = 0.58) for OS with sunitinib. In conclusion, in metastatic renal cell cancer, axitinib, sunitinib and temsirolimus demonstrate specific toxicities that are protective OS/PFS predictors.

Until recently, the sole treatment for patients with nonmetastatic renal cell carcinoma (RCC) was nephrectomy followed by observation. As metastatic RCC (mRCC) remains largely incurable (5-year survival rate ∼12%), adjuvant treatment, with potential to prevent/delay disease recurrence, is needed. In November 2017, sunitinib was approved in the USA as the first adjuvant therapy for patients at high risk for recurrent RCC postnephrectomy based on results from the S-TRAC trial. Patients eligible for adjuvant treatment have no evidence of disease and may be less willing to tolerate side effects. Therefore, proactive adverse event management is critical for keeping patients on adjuvant treatment and requires understanding the subtle differences in the adverse event profile of sunitinib in the adjuvant versus metastatic RCC setting.

Ripretinib (DCC-2618) is a novel, type II tyrosine switch control inhibitor designed to broadly inhibit activating and drug-resistant mutations in KIT and PDGFRA . Ripretinib has emerged as a promising investigational agent for the treatment of gastrointestinal stromal tumor owing to targeted inhibition of secondary resistance mutations that may develop following treatment with prior line(s) of tyrosine kinase inhibitors. Here we describe the rationale and design of intrigue (NCT03673501), a global, randomized (1:1), open-label, Phase III study comparing the safety and efficacy of ripretinib versus sunitinib in patients with advanced gastrointestinal stromal tumor following imatinib. The primary end point is progression-free survival and key secondary objectives include objective response rate and overall survival. Clinical Trial Registration: NCT03673501.

The optimal dosing schedule to maintain the effectiveness of sunitinib for metastatic renal cell carcinoma - while reducing toxicity - remains an important clinical question. A meta-analysis of randomized trials and observational studies assessed the relative treatment effects of 4/2, 2/1 and transitional-2/1 schedules on outcomes and adverse events using Bayesian network meta-analysis methods. Treatment with 2/1 reduced the risk of disease progression or death by 25% and had lower odds of hand-and-foot syndrome compared with the 4/2. A numerical but not 'statistical' benefit in progression-free survival was observed with the transitional-2/1 compared with 4/2. Alternative schedules with the 2/1 and transitional-2/1 may be more clinically beneficial in metastatic renal cell carcinoma than the 4/2 schedule.

Aim: Evaluate associations between clinical outcomes and SNPs in patients with well-differentiated pancreatic neuroendocrine tumors receiving sunitinib. Patients & methods: Kaplan-Meier and Cox proportional hazards models were used to analyze the association between SNPs and survival outcomes using data from a sunitinib Phase IV (genotyped, n = 56) study. Fisher's exact test was used to analyze objective response rate and genotype associations. Results: After multiplicity adjustment, progression-free and overall survivals were not significantly correlated with SNPs; however, a higher objective response rate was significantly associated with IL1B rs16944 G/A versus G/G (46.4 vs 4.5%; p = 0.001). Conclusion: IL1B SNPs may predict treatment response in patients with pancreatic neuroendocrine tumors. VEGF pathway SNPs are potentially associated with survival outcomes.

Aim: To describe the long-term safety of sunitinib in patients with progressive, well-differentiated, advanced/metastatic pancreatic neuroendocrine tumors., Patients & Methods: Sunitinib- and placebo-treated patients from the Phase III study continued to receive sunitinib (37.5 mg on a continuous daily-dosing regimen) in two open-label extension studies., Results: Median (range) treatment exposure: 30.2 (0.7-269.4) and 87.1 (3.9-319.4) weeks for medium-term (n = 41) and long-term-treated (n = 61) populations, respectively. All patients experienced ≥1 adverse event (AE); 47 (45.6%) reported serious AEs. Common all-causality AEs: diarrhea (63.1%); neutropenia (43.7%); abdominal pain (40.8%). Fifteen (14.6%) patients discontinued treatment due to treatment-related AEs., Conclusion: The safety of extended sunitinib treatment was consistent with the known safety profile of sunitinib in pancreatic neuroendocrine tumors.