Sex differences on multikinase inhibitors toxicity in patients with advanced gastroenteropancreatic neuroendocrine tumours.

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.

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Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jorge Hernando: Speakers Bureau: Angelini, Leo, Eisai, Adacap, Novartis, Pfizer, Advanz, Ipsen. Alejandro García-Alvarez: Speakers Bureau: Angelini. Travel/Accommodation, Expenses: Pfizer, Ipsen, EISAI, Advanz, AAA. Toni Ibrahim: Advisory board (Amgen, Galxosmithkline and Pharmamar). Cover Participation at scientific meeting (Istituto gentili and Pharmamar). Enrique Grande: EG has received honoraria for speaker engagements, advisory roles or funding of continuous medical education from Adacap, AMGEN, Angelini, Astellas, AstraZeneca, Bayer, Blueprint, Bristol Myers Squibb, Caris Life Sciences, Celgene, Clovis-Oncology, Eisai, Eusa Pharma, Genetracer, Guardant Health, HRA-Pharma, IPSEN, ITM-Radiopharma, Janssen, Lexicon, Lilly, Merck KGaA, MSD, Nanostring Technologies, Natera, Novartis, ONCODNA (Biosequence), Palex, Pharmamar, Pierre Fabre, Pfizer, Roche, Sanofi Genzyme, Servier, Taiho, and Thermo Fisher Scientific. EG has received research grants from Pfizer, AstraZeneca, Astellas, and Lexicon Pharmaceuticals. Eric Raymond: Consulting and Share holder for Genoscience Pharma, StromaCare, SCOR life science. Share Holder at Neuronax. Scientific and steering committee at Onward Therapeutics and BeiGen. Received travel grant for data presentation from BeiGen. Rocio Garcia-Carbonero: RGC has provided scientific advice and/or received honoraria or funding for continuous medical education from AAA-Novartis, Advanz Pharma, Amgen, Bayer, BMS, Boerhinger, Esteve, Hutchmed, Ipsen, Merck, Midatech Pharma, MSD, PharmaMar, Pierre Fabre, Roche, Servier and Sanofi, and has received research support from Pfizer, BMS and MSD. Ramon Salazar: Invited speaker: Advanced Accelerator Applications, Amgen, Astellas, Bayer, BMS, Eisai, GSK, Janssen Oncology, Lilly, Pierre Fabre, Roche, Sanofi Genzyme. Expert testimony: AstraZeneca, Celgene, Merck, MSD, Novartis, Pfizer. Advisory Board: Agendia, Amgen, Ferrer, Guardant Health, Ipsen, Lilly, Merck, MSD, Novartis, Pfizer, Roche Diagnostic, Roche Farma, Tayhoo, VCN-BCN. Alex Teule: Speakers Bureau: AAA, Pfizer, Ipsen, Novartis, AstraZeneca. Travel, Accommodation, Expenses: AAA, Pfizer, Ipsen, Novartis, AstraZeneca. Salvatore Tafuto: S.Tafuto has provided scientific advice and/or received honoraria or funding for continuous medical education from AAA-Novartis, Boerhinger, Ipsen, Merck, PharmaMar and has received research support from NOVARTIS, IPSEN. Vicente Alonso: VA has provided scientific advice and/or received honoraria or funding for continuous medical education from AAA-Novartis, Amgen, Ipsen, Merck, Pierre Fabre, Roche, Servier and Sanofi. Daniel Castellano: Advisory role Lilly, Pierre Fabre, Boehringer Ingelheim, Roche/Genentech, AstraZeneca, Ipsen, Bayer, Sanofi, Janssen Oncology, Pfizer, Bristol Myers Squibb, Astellas Pharma, Novartis, MSD Oncology, Sanofi. The rest of the authors declare no conflict of interest for this publication.