Sex and gender influence on adverse events for melanoma patients: A comprehensive review and meta-analysis.

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e21542 Background: Immunotherapy and target therapy have revolutionized melanoma treatment. However, adverse events (AEs) are still frequent and might impact treatment adherence. Female sex was demonstrated to be associated with a higher risk of AEs from cytotoxic therapy related to cancer treatment. This study aims to conduct a systematic review and meta-analysis to investigate Sex and Gender (S/G) effect on adverse events. Methods: We extracted data from independent studies published until April 2024 with information regarding toxicity by S/G. Only studies that involved patients with melanoma as primary disease were included. Summary Odds ratios OR (sOR) estimates were obtained through random-effects models, and 95% Confidence Intervals (CI) were estimated. I 2 was used to evaluate the between-study heterogeneity. Publication bias was investigated with Begg and Egger tests. Results: Information regarding toxicity and gender were extracted from seventy articles. A significant increase in AE related to the thyroid was observed in women (sOR = 2.01, 95%CI [1.41-2.85], I² = 29). S/G did not affect Grade III-IV, Dermatological, Gastrointestinal, Hypophyses, Kidney, Liver or Ocular toxicities. The increased risk of AE related to the thyroid was mainly seen in those undergoing first-line treatments, sOR = , 2.16 [1.36-3.42], and those who underwent mono and combo therapy. Women undergoing TT (target therapy) had an increased risk of dermatological (sOR = 1.94, 95%CI 1.51-2.50, I² = 0%) AE. Conclusions: This study supports and extends the discussion on the impact of S/G on the development of toxicities. Women have an increased risk of AE related to the thyroid, mainly seen during first-line treatment, and showed an increased risk of dermatological AE when treated with TT. Women should be monitored closely for precursor signs of thyroid-related AE, as well as dermatological and generally severe AE, to preserve good treatment adherence.

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