PCN265 TARGETED REVIEW OF ADVERSE EVENTS ASSOCIATED WITH TREATMENTS FOR STAGE 3 AND 4 MELANOMA

Abstract

Chemotherapy, immunotherapy and targeted therapy are recommended treatments for patients with stage 3 and 4 melanoma. Despite their efficacy, all are associated with adverse events (AEs), which may be costly to manage. Data published in the past five years on AEs associated with these treatments have not been compared. This study aimed to identify and compare the most frequently reported AEs associated with these treatments in stage 3 and 4 melanoma. Targeted searches were conducted in PubMed to identify phase 3 studies reporting AEs associated with chemotherapies, immunotherapies and targeted therapies used in the treatment of stage 3 and 4 melanoma published in the past five years (January 1, 2014 to December 31, 2018). Study titles and abstracts were screened by two independent reviewers. Study design details and data on AEs by treatment were extracted. AEs occurring in >10% of patients were recorded, in addition to grade ≥3 AEs occurring in >1% of patients. Twenty-six phase 3 studies reporting AEs associated with chemotherapies, immunotherapies or targeted therapies as treatment for stage 3 and 4 melanoma were included; all categorized AEs by grade (e.g., all, 1-2, >3). The following treatments were included: chemotherapy: dacarbazine+placebo; chemotherapy+targeted therapy: dacarbazine+selumetinib; immunotherapy: ipilimumab, ipilimumab+placebo, nivolumab, nivolumab+placebo, pembrolizumab, talimogene laherparepvec, nivolumab+ipilimumab; targeted therapy: dabrafenib+placebo, vemurafenib, and dabrafenib+trametinib. Across treatments, the most frequently reported all-grade and grade >3 AEs were comparable; although there were some differences (e.g., rash was more frequently reported for targeted therapies than immunotherapies). Certain all-grade AEs were associated with particular therapies: diarrhea with nivolumab+ipilimumab (44-45% of patients), and pyrexia with dabrafenib+trametinib (52-63% of patients). Data from the last five years show that treatments for stage 3 and 4 melanoma are associated with high rates of AEs. There is still substantial unmet need for treatments with improved safety profiles.