4% w/w Fluorouracil Sodium Cream (Tolak)

Key Messages

• Canada’s Drug Agency (CDA-AMC) recommends that Tolak be reimbursed by public drug plans for the topical treatment of actinic keratosis lesions of the face, ears, and/or scalp if certain conditions are met.
• The subcommittee determined that Tolak demonstrates acceptable clinical value compared with fluorouracil 5% cream in patients with actinic keratosis lesions of the face, ears, and/or scalp. This determination was enough for the Canadian Drug Expert Committee (CDEC) to recommend that Tolak be reimbursed.
• Evidence from a pivotal phase III trial, Study 48, demonstrated that 4 weeks of treatment with Tolak in patients with actinic keratosis lesions of the face, ears, and/or scalp likely resulted in similar clinical benefit compared with fluorouracil 5% cream, as measured by the proportion of patients achieving at least 75% clearance and by the percent change from baseline in total lesion counts assessed 4 weeks after completing treatment. However, Study 48 did not demonstrate noninferiority of Tolak for the primary end point of the proportion of patients achieving 100% clearance at 4 weeks off treatment. Due to the nature of actinic keratosis, the clinical expert consulted by CDA-AMC for this review noted that achieving at least 75% clearance is a more meaningful end point in clinical practice for evaluating the efficacy of Tolak in the treatment of actinic keratosis lesions of the face, ears, and/or scalp compared with 100% clearance. On this basis, it was concluded that Tolak is likely comparable to fluorouracil 5% cream. In addition, evidence from another pivotal phase III trial, Study 49, demonstrated superiority of Tolak over its vehicle for the primary end point and all secondary end points. Overall, the observed safety profile of Tolak is consistent with the product monograph and clinical expert input.
• Tolak should only be covered for topical treatment in patients with actinic keratosis lesions of the face, ears, and/or scalp. Eligibility for reimbursement of Tolak should be similar to each public drug plan’s current initiation criteria for fluorouracil 5% cream for the topical treatment of actinic keratosis of the face, ears, and/or scalp.
• Tolak should only be reimbursed if each public drug plan’s current renewal, discontinuation, and prescribing criteria for fluorouracil 5% cream for the topical treatment of actinic keratosis of the face, ears, and/or scalp are met and the total cost of Tolak does not exceed the total cost of treatment with fluorouracil 5% cream.