Efficacy and safety of nilotinib in patients with KIT-mutated metastatic or inoperable melanoma: final results from the global, single-arm, phase II TEAM trial

Background: The single-arm, phase II Tasigna Efficacy in Advanced Melanoma (TEAM) trial evaluated the KIT-selective tyrosine kinase inhibitor nilotinib in patients with KIT-mutated advanced melanoma without prior KIT inhibitor treatment. Patients and methods: Forty-two patients with KIT-mutated advanced melanoma were enrolled and treated with nilotinib 400mg twice daily. TEAM originally included a comparator arm of dacarbazine (DTIC)-treated patients;the design was amended to a single-arm trial due to an observed low number of KIT-mutated melanomas. Thirteen patients were randomized to DTIC before the protocol amendment removing this study arm. The primary endpoint was objective response rate (ORR), determined according to Response Evaluation Criteria In Solid Tumors. Results: ORR was 26.2% (n = 11/42;95% CI, 13.9%-42.0%), sufficient to reject the null hypothesis (ORR <= 10%). All observed responses were partial responses (PRs;median response duration, 7.1 months). Twenty patients (47.6%) had stable disease and 10 (23.8%) had progressive disease;1 (2.4%) response was unknown. Ten of the 11 responding patients had exon 11 mutations, four with an L576P mutation. The median progression-free survival and overall survival were 4.2 and 18.0 months, respectively. Three of the 13 patients on DTIC achieved a PR, and another patient had a PR following switch to nilotinib. Conclusion: Nilotinib activity in patients with advanced KIT-mutated melanoma was similar to historical data from imatinib-treated patients. DTIC treatment showed potential activity, although the low patient number limits interpretation. Similar to previously reported results with imatinib, nilotinib showed greater activity among patients with an exon 11 mutation, including L576P, suggesting that nilotinib may be an effective treatment option for patients with specific KIT mutations

Safety and efficacy of sunitinib in patients from Latin America: subanalysis of an expanded access trial in metastatic renal cell carcinoma

Carlos H Barrios,1 Daniel Herchenhorn,2 Mat&iacute;as Chac&oacute;n,3 Paula Cabrera-Galeana,4 Peter Sajben,5 Ke Zhang6 1Department of Medicine, PUCRS School of Medicine, Porto Alegre, 2Division of Clinical Oncology, Instituto Nacional do C&acirc;ncer, Rio de Janeiro, Brazil; 3Clinical Oncology, Alexander Fleming Institute, Buenos Aires, Argentina; 4Department of Medical Oncology, Instituto Nacional de Cancerolog&iacute;a, M&eacute;xico, Centro Oncol&oacute;gico Issemym Edomex, M&eacute;xico; 5Pfizer Oncology, New York, NY, 6Pfizer Oncology, La Jolla, CA, USA Background: Sunitinib is an approved treatment for metastatic renal cell carcinoma (mRCC). The safety profile and efficacy of sunitinib were confirmed in a global expanded access trial (ClinicalTrials.gov&nbsp;identifier: NCT00130897). This report presents a subanalysis of the final trial data from patients in Latin America.Methods: Treatment-na&iuml;ve or previously treated mRCC patients aged &ge;18 years received oral sunitinib at a starting dose of 50&nbsp;mg/day on a 4-weeks-on/2-weeks-off schedule. Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent. Safety was assessed regularly, and tumor measurements were scheduled per local practice (using Response Evaluation Criteria in Solid Tumors).Results: In total, 348 patients from Latin America received sunitinib. Overall, 75% of patients had two or more sites of metastatic disease, 28% were aged &ge;65 years, 14% had an Eastern Cooperative Oncology Group performance status &ge;2, 9% had brain metastases, 9% had no prior nephrectomy, and 5% had non-clear cell RCC. Median treatment duration was 8 months, and median follow-up was 15.1 months. In total, 326 patients (94%) discontinued treatment, primarily due to death (41%) or lack of efficacy (22%). Most treatment-related adverse events were of mild to moderate severity (grade 1/2). Mucosal inflammation (reported in 54% of patients), diarrhea (53%), and asthenia (41%) were the most common any-grade treatment-related adverse events. Asthenia (12%), neutropenia (10%), and fatigue and thrombocytopenia (both 9%) were the most common grade 3/4 treatment-related adverse events. In total, 311&nbsp;patients were included for tumor response, of whom eight (3%) had a complete response and 46 (15%) a partial response, yielding an objective response rate of 17%. Median duration of response, progression-free survival, and overall survival were 26.7, 12.1, and 16.9 months, respectively.Conclusion: The efficacy and safety profile of sunitinib in patients with mRCC from Latin America was comparable to that in the entire cohort of the global expanded access trial. Keywords: sunitinib, kidney cancer, expanded-access trial, Latin America, tyrosine kinase inhibito