Safety Of Nilotinib In Patients Research Articles

Monitoring the safety of nilotinib in patients with chronic myeloid leukemia

The aim of the study was to evaluate the safety profile of nilotinib administered to chronic myeloid leukemia (CML) at patients. The study was conducted from March 2018 to May 2019 and it included 20 patients with CML in chronic phase. Of these 20 patients, 17 had previously been treated with imatinib and 3 with hydroxyurea. The mean duration of treatment with Nilotinib was 6.75 months. In nine patients treated with nilotinib (400 mg), 55% complained of fatigue, 33% of headache and 22.2% of pruritus. In five patients treated with Nilotinib (600 mg), 20% complained of headache, 40% of fatigue and 20% of pruritus. In addition, in six patients treated with nilotinib (800 mg), 50% complained of headache and fatigue, 17% with pruritus and visual disorder was observed in 20% of cases. In the study, the adverse reactions were observed between the age of 20 and 40 and it was 7.1%, in contrast to the group of patients between the age of 40 and 60 where the incidence of adverse reactions was 21.42%. The incidence of adverse reactions in patients in the age group over 60 years it was 57.1%. In terms of gender, the incidence of adverse reactions was equal to 50% for both men and women. In conclusion, this study showed that treatment with nilotinib was well tolerated, with adverse reactions of an easy degree. Future evaluation is necessary in order to understanding the adverse reaction of nilotinib in comparison with other tyrosine kinase inhibitors. Keywords: nilotinib, pharmacovigilance, safety, chronic myeloid leukemia

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

BackgroundThe 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 methodsForty-two patients with KIT-mutated advanced melanoma were enrolled and treated with nilotinib 400 mg 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.ResultsORR 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.ConclusionNilotinib 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.Clinical Trial RegistrationClinicalTrials.gov, NCT01028222.

Efficacy and Safety of Nilotinib 300 Mg Twice Daily (BD) in Patients with CML in Chronic Phase (CML-CP) Who Are Intolerant to Prior BCR-ABL Tyrosine Kinase Inhibitors (TKIs): Results from the Randomized, Phase IIIb E.N.E.S.Tswift Study

Background : Philadelphia chromosome-positive (Ph+) CML is a myeloproliferative disease characterized by the presence of the abnormal Ph+ in hematopoietic cells. Imatinib, dasatinib and nilotinib are BCR-ABL TKIs commonly used in the treatment of CML-CP. Many patients on BCR-ABL TKI therapy will experience adverse events (AEs). Some of the more common AEs associated with first- and second-generation BCR-ABL TKIs include fluid retention, diarrhea, rash, musculoskeletal pain, nausea, vomiting, muscle cramps, and headache. Some patients will be unable to tolerate these AEs and will discontinue therapy. The current study aimed to assess the efficacy and safety of nilotinib in patients with CML-CP who are responsive to but intolerant of treatment with imatinib or dasatinib. Although the study was stopped early due to low recruitment, here we present results on cross-intolerance and molecular response in the patients who were switched from imatinib or dasatinib to nilotinib. Methods : Eligible adult patients had: Ph+ CML-CP associated with BCR-ABL quantifiable by real-time quantitative reverse transcriptase-polymerase chain reaction (RQ-PCR); received ≥3 months imatinib or dasatinib or both; were Results: The study was stopped early due to low recruitment; 20 patients were enrolled (mean age 53.9 years [range 31-77]; 14 female). 16 patients had received prior imatinib therapy, 4 patients prior dasatinib. Median nilotinib treatment duration was 494 days (mean 480, SD 167.6 days). At screening, 30% of patients were not in MMR, 45% had MMR and 25% had MR4.0. By month 3 and 24 of nilotinib treatment, 55% (11/20) and 65% (13/20) of patients, respectively, achieved at least a 1 log reduction in BCR-ABL levels. 35% (7/20) of patients achieved MR4.5 between baseline and month 3 of nilotinib treatment, and 50% (10/20) achieved MR4.5 at any time up to month 24. The proportion of patients with a molecular response at each visit up to month 15 is shown in the Figure. AEs during prior treatment with imatinib and dasatinib included gastrointestinal events (nausea, vomiting, diarrhea), superficial edema, myalgia, fatigue, rash, and headache, among others. 68% of AEs had resolved by month 3 of nilotinib treatment. Among the 13 evaluable patients on prior imatinib, 7 (54%) had resolution of all AEs during treatment with nilotinib; of 3 evaluable patients on prior dasatinib, 3 (100%) had AE resolution on nilotinib. Grade 3/4 AEs during nilotinib therapy occurred in 3 patients: diabetes mellitus, fatigue, neutropenia, pneumonia, osteoarthritis, and hyperuricemia. Conclusions : Although early termination of the study has not allowed for a robust analysis, these results suggest that nilotinib is effective and well tolerated in most patients intolerant of imatinib or dasatinib. During the first 3 months of switching to nilotinib, 55% of patients had achieved at least a 1 log reduction in BCR-ABL levels, and 35% of patients had achieved MR4.5. The cumulative rate of MR4.5 by 24 months was 50%. Achievement of this endpoint has been linked to favorable long-term outcomes, such as treatment-free remission. Furthermore, the majority of the AEs had resolved by month 3 of nilotinib therapy. This improved tolerance to nilotinib may result in improved treatment adherence. As such, although further study in a larger population is needed for confirmation, these results provide further evidence that nilotinib is a favorable option to establish a molecular response in patients intolerant of imatinib or dasatinib. Disclosures D9Rozario: BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Branford: Qiagen: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding; Ariad: Research Funding; Novartis: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Cepheid: Consultancy. Yeung: Ariad: Research Funding; Novartis Pharmaceuticals: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding. Anderson: Novartis Pharmaceuticals: Employment. Gervasio: Novartis Pharmaceuticals: Employment. Hughes: Novartis: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding.