The results of the phase III SWITCH trial showed no difference in the efficacy of sorafenib sequential to sunitinib or both in reverse order for the treatment of metastatic renal cell carcinoma. Progression-free survival and overall survival outcomes were similar between the two dosing sequences, and safety profiles were the same as previously reported. The results of the study were presented at the Gastrointestinal Symposium in San Fransisco. According to first author Dr. Maurice Stephan of the University of Mannheim, Germany, this is the first randomized prospective trial of sorafenib/sunitinib vs. sunitinib/sorafenib in first-line sequential treatment of advanced or metastatic renal cell carcinoma. The trial’s primary objective was not achieved, and superior overall progression-free survival was seen with both dosing sequences. Overall survival was similar for patients in both treatment arms, and safety performance was promising. Details of the SWITCH trial The SWITCH trial is a prospective, open-label, randomized phase 3 trial conducted in collaboration with investigators from Germany, Australia, and New Zealand. A total of 365 patients with advanced or metastatic renal cell carcinoma who were not receiving cytokine therapy or prior systemic therapy were enrolled in the study. Subjects were randomized in a 1:1 ratio to receive soratinib or sunitinib, respectively, and crossed over to second-line treatment with sunitinib or sorafenib, respectively, when disease progressed or when toxicity became intolerable. The primary endpoint of the trial was overall progression-free survival, defined as confirmed disease progression or death from trial randomization to second-line treatment. At baseline, patient demographics and disease characteristics were similar in both treatment groups. The median age was approximately 64 years, approximately 75% were male patients, and approximately 86% had clear cell disease. The majority of patients were classified as intermediate-risk according to Memorial Sloan Kettering Cancer Center criteria, however the number of patients in the sunitinib/sorafenib treatment group was slightly higher in favorable-risk patients, 44.8 percent and 39 percent in the two groups, respectively. At the end of the trial, 11% of patients in the sunitinib/sorafenib arm remained on first-line sunitinib and 9% of patients in the sorafenib/sorafenib arm remained on first-line sorafenib. Forty-two percent of patients in the sunitinib/sorafenib arm eventually crossed over to second-line therapy, and 57% of patients in the sorafenib/sunitinib arm crossed over to second-line therapy. At the end of the trial, 3 percent and 7 percent of patients in the two groups, respectively, were still on second-line therapy. Key findings The study found no significant differences in overall progression-free survival between the two treatment groups for the primary endpoint. The median overall progression-free survival was 12.5 months in the sorafenib/sunitinib arm and 14.9 months in the sunitinib/sorafenib arm. Overall survival was also not significantly different between the two groups. Median overall survival in the sorafenib/sunitinib and sunitinib/sorafenib treatment groups was 31.5 months and 30.2 months, respectively. Current treatment regimens make it difficult for patients to achieve overall survival beyond 30 months, according to the investigators. However, this is already the longest survival recorded for patients with metastatic renal cell carcinoma. Evaluation of second-line treatment showed a significant difference in disease control rates between the two treatment groups, with the sorafenib/sonitinib group being more favorable, at 48.5% vs. 31.6% in the two groups, respectively. However, these results may be biased. The authors noted that more patients in the sorafenib/sonitinib treatment group received second-line treatment (56.6% vs. 41.5% in the two groups, respectively). Adverse effects Patients had different side effects after first-line treatment, as expected by the investigators. Diarrhea and skin reactions were more common with first-line treatment with sorafenib, while nausea and stomatitis were more common with first-line treatment with sunitinib. Adverse events were less common during second-line treatment compared to first-line treatment, which may reflect the “survival of the fittest” principle. Neither drug is cardiotoxic. Background Most patients in Europe and the United States are first treated with sunitinib, which is considered to be the most effective treatment option. If disease progression occurs despite treatment with sunitinib, we use temsirolimus or sorafenib as second-line therapy, followed by third-line therapy. We are trying to generalize the best dosing sequence through clinical trials. This is how treatment is categorized in the United States and Europe: for patients with a good or intermediate prognosis, first-line treatment is primarily sunitinib, with bevacizumab + IFN as a second option; for patients with a poorer prognosis, the primary evidence-based medicine is the phase III clinical study of temsirolimus, but sunitinib is also an option. Sorafenib has been used in numerous studies in patients who have received conventional therapy as a control versus placebo. Small sample clinical trials comparing the efficacy of sorafenib with IFN in first-line treatment showed that sorafenib was not superior to IFN, suggesting that it was not successful in first-line treatment. As a result, sorafenib is used selectively in the United States in people who are intolerant to other treatments, but more often in second- or third-line therapy. Sunitinib is being investigated in a broader range of oncology therapeutic areas, including lung cancer, breast cancer, and other solid tumors. It is often combined with chemotherapy in the treatment of these cancers. And among the currently approved indications is also gastrointestinal mesenchymal tumor.