On October 28, 2015, the U.S. Food and Drug Administration approved ipilimumab (Yervoy Injection), for the additional indication of adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy.
The approval was based on improvement in recurrence-free survival (RFS) in a randomized (1:1), double-blind, placebo-controlled trial in 951 patients with resected Stage IIIA (lymph node >1 mm), IIIB, and IIIC (with no in-transit metastases) histologically confirmed cutaneous melanoma.
The primary efficacy endpoint was RFS determined by an independent review committee. The median RFS was 26 and 17 months in the ipilimumab (n=475) and placebo (N=476) arms, respectively [HR 0.75 (95% CI: 0.64, 0.90), p <0.002, stratified log-rank test].
Safety data was evaluated in 945 patients (median age 51 years, 62% male), who received ipilimumab 10 mg/kg (n=471) or placebo (n=474) administered as an intravenous infusion for 4 doses every 3 weeks followed by 10 mg/kg every 12 weeks beginning at week 24 up to a maximum of 3 years. Ipilimumab-treated patients received a median of4 doses (range: 1 to 16) and 36% of patients received ipilimumab for longer than 6 months. Ipilimumab was discontinued for adverse reactions in 52% of patients.
The most common adverse reactions included rash, pruritus, diarrhea, nausea, colitis, vomiting, weight loss, fatigue, pyrexia, headache, decreased appetite, and insomnia.
Grade 3-5 immune mediated adverse reactions occurred in 41% of ipilimumab-treated patients which included enterocolitis (16%), hepatitis (11%), endocrinopathy (8%) dermatitis (4%), and neuropathy (1.7%). The five treatment-related deaths were due to immune-mediated adverse reactions of enterocolitis (3), Guillain-Barré syndrome (1) and myocarditis (1).
Patients should be assessed for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and evaluate clinical chemistries, including liver function tests, adrenocorticotropic hormone (ACTH) level, and thyroid function tests, at baseline and before each dose.
The recommended dose and schedule for ipilimumab for adjuvant treatment of melanoma is 10 mg/kg administered intravenously over 90 minutes every 3 weeks for 4 doses followed by 10 mg/kg every 12 weeks for up to 3 years. In the event of toxicity, doses are omitted, not delayed.
Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125377s073lbl.pdf
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online athttp://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).
No hay comentarios:
Publicar un comentario