Gastrointestinal and Endocrine Tumor Unit, Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Gastrointestinal and Endocrine Tumor Unit, Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Eur J Cancer. 2023 Jul;188:39-48. doi: 10.1016/j.ejca.2023.04.013. Epub 2023 Apr 23.
There is an increasing interest in the role of sex and gender in cancer patients. The impact of sex differences in oncological systemic therapies is still unknown, and there is a lack of evidence specially in uncommon neoplasms like neuroendocrine tumours (NET). In the present study, we combine the differential toxicities by sex in five published clinical trials with multikinase inhibitors (MKI) in gastroenteropancreatic (GEP) NET.
We performed a pooled univariate analysis of reported toxicity in patients treated in five phase 2 and phase 3 clinical trials with MKI in the GEP NET setting: sunitinib (SU11248, SUN1111), Pazopanib (PAZONET), sorafenib-bevacizumab (GETNE0801) and Lenvatinib (TALENT). Differential toxicities between male and female patients were evaluated considering relationship with study drug and different weights of each trial by random effect adjustment.
We found nine toxicities which were more frequent in female patients (leukopenia, alopecia, vomiting, headache, bleeding, nausea, dysgeusia, neutrophil count decreased and dry mouth) and two toxicities being more frequent in male patients (Anal Symptoms and Insomnia). Asthenia and diarrhoea were the only severe (Grade 3-4) toxicities more frequent in female patients.
Sex-related differences in toxicity with the MKI treatment require targeted information and individualised management of patients with NET. Differential reporting of toxicity should be promoted when clinical trials are published.
人们对癌症患者中性别和性别差异的作用越来越感兴趣。肿瘤系统治疗中性别差异的影响尚不清楚，特别是在神经内分泌肿瘤（NET）等罕见肿瘤中，证据不足。在本研究中，我们结合了五种已发表的多激酶抑制剂（MKI）治疗胃肠胰腺（GEP）NET 的临床研究中按性别划分的毒性差异。
我们对五种用于 GEP NET 中 MKI 的 2 期和 3 期临床试验报告的毒性进行了汇总单变量分析：舒尼替尼（SU11248，SUN1111）、帕唑帕尼（PAZONET）、索拉非尼-贝伐珠单抗（GETNE0801）和仑伐替尼（TALENT）。通过随机效应调整，考虑与研究药物的关系和每个试验的不同权重，评估男性和女性患者之间的毒性差异。
我们发现了九种在女性患者中更为常见的毒性（白细胞减少症、脱发、呕吐、头痛、出血、恶心、味觉障碍、中性粒细胞计数减少和口干）和两种在男性患者中更为常见的毒性（肛门症状和失眠）。乏力和腹泻是唯一更为常见的女性患者重度（3-4 级）毒性。
NET 患者接受 MKI 治疗时的毒性存在性别差异，需要针对性的信息和个体化的管理。在发表临床试验时，应促进毒性的差异报告。
