Abstract 3931
Background
There is a dearth of understanding of gender influence in targeted therapies toxicity. Increasing evidence suggests a possible different toxicity profile according to gender, but mostly retrospective studies in common tumors. Currently, data from prospective studies are minimal. In the present study, we will review MKI toxicity profiles according to gender in pts with NETs in three clinical trials.
Methods
Multicenter open-label phase II studies TALENT, PAZONET and GETNE0801 included pts with advanced GEP NETs treated with lenvatinib, pazopanib, and sorafenib-bevacizumab respectively. All studies were performed by the Spanish Task Force Group for Neuroendocrine Tumors (GETNE). All pts were included in the review, considering all toxicity grades with an incidence higher than 5% for the univariate analysis. Bevacizumab specific toxicities were excluded in patients from GETNE0801 trial. Additionally, all grade 3-4 toxicities were analyzed separately.
Results
199 pts (46.23% female) with 1349 adverse events (AEs) (12.23% G3-4) divided into 125 categories were included. In female patients, nausea/vomiting, skin disorders (excluding palmar-plantar erythrodysesthesia), liver alterations (including transaminase and bilirubin), headache, pyrexia, hair disorders and dizziness were significantly more common (Table). The only toxicity with a higher incidence in men was dysphonia (OR 0.42, 95% CI 0.2-0.9, p0.02). The only G3-4 toxicity significantly more frequent in women was liver toxicity (20.65% vs. 7.55%, OR 3.18, p0.009).Table: 1387P
Toxicity (all grades) | Women (%) | Men (%) | Difference (%) | Odds Ratio (95% CI) | p |
---|---|---|---|---|---|
Nausea/Vomiting | 63.04 | 44.86 | 18 | 2.09 | 0.01 |
Skin disorders | 60.87 | 45.79 | 15 | 1.84 | 0.03 |
Liver toxicity | 57.61 | 30.84 | 26 | 3.04 | 0.0002 |
Headache | 28.26 | 12.15 | 16 | 2.84 | 0.005 |
Pyrexia | 17.39 | 5.61 | 11 | 3.44 | 0.01 |
Hair disorders | 20.65 | 8.41 | 12 | 2.83 | 0.01 |
Dizziness | 17.39 | 6.54 | 10 | 3.00 | 0.02 |
Dysphonia | 16.30 | 37.38 | 21 | 0.32 | 0.001 |
Conclusions
In our study, we observed significant differences in toxicity AEs by gender, especially in women with seven increased toxicities. A different approach in toxicity management should be adopted based on gender in pts with GEP NETs treated with MKI.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J. Hernando Cubero: Speaker Bureau / Expert testimony: Eisai, Ipsen, Roche, Angelini, ; Travel / Accommodation / Expenses: Ipsen, Novartis, AAA, Roche, AstraZeneca, Eisai. E. Grande: Speaker Bureau / Expert testimony: Pfizer, Ipsen, BMS, Eisai, Roche, MSD, Sanofi, Adacap, Novartis, EUSA Pharma, Pierre Fabre, Lexicon, Celgene; Research grant / Funding (institution): MSD, Roche. T. Ibrahim: Advisory / Consultancy: Eisai; Research grant / Funding (institution): Novartis; Travel / Accommodation / Expenses: Ipsen, PharmaMar, Novartis. J.W. Valle: Advisory / Consultancy: Abbott, Agios, AstraZeneca, Baxalta, Bioven, Celgene, Delcath, Genoscience Pharma, Incyte, Ipsen, Keocyt, Lilly, Merck, MidaTech, Mundipharma, Novartis, NuCana, PCI Biotech, Pfizer, Pieris Pharmaceuticals, QED Pharmaceuticals; Speaker Bureau / Expert testimony: Abbott, Celgene, Ipsen, Novartis, Pfizer, Sirtex; Travel / Accommodation / Expenses: Celgene, Ipsen, Novartis, NuCana. V. Alonso: Advisory / Consultancy: Amgen, Roche, Merck, Servier, Sanofi, Ipsen, Bayer, Novartis. R. Manneh Kopp: Speaker Bureau / Expert testimony: Pfizer, Ipsen, BMS, Roche, MSD, Sanofi, Novartis; Research grant / Funding (institution): MSD, Roche, BMS. R. Salazar: Advisory / Consultancy: VCN-BCN, Agendia, Guardant Health, Roche Diagnostics, Ferrer, Pfizer, Novartis, Ipsen, Amgen, Merck, Roche Farma, Lylli, MSD; Speaker Bureau / Expert testimony: Pfizer, Amgen, Novartis, Merck, MSD, AZD, Celgene,. J. Capdevila: Honoraria (self): Novartis, Pfier, Ipsen, Exelixis, Bayer, Eisai, AAA, Amgen, Sanofi, Merck; Research grant / Funding (institution): Eisai, Novartis, Ipsen, AstraZeneca, Pfier, AAA. All other authors have declared no conflicts of interest.
Resources from the same session
3240 - Efficacy and safety of trifluridine/tipiracil (FTD/TPI) in European patients with heavily pretreated metastatic gastric cancer (mGC): an analysis of the TAGS study
Presenter: Maria Alsina
Session: Poster Display session 2
Resources:
Abstract
733 - Clinical experience: ramucirumab with FOLFIRI/XELIRI as a second line for patients with metastatic gastric cancer
Presenter: Tatiana Titova
Session: Poster Display session 2
Resources:
Abstract
2186 - Efficacy and safety of apatinib for the treatment of AFP-producing gastric cancer
Presenter: Ningning Li
Session: Poster Display session 2
Resources:
Abstract
3172 - Apatinib in combination with docetaxol and S1 chemotherapy in the first line treatment of metastatic gastric cancer
Presenter: Ling Xia
Session: Poster Display session 2
Resources:
Abstract
3982 - Parameters of local cellular immunity in metastatic gastric cancer
Presenter: Aleksandr Sagakyants
Session: Poster Display session 2
Resources:
Abstract
5102 - Germline pathogenic mutations in Chinese patients with gastric cancer identified by next-generation sequencing (NGS)
Presenter: Xiaotian Zhang
Session: Poster Display session 2
Resources:
Abstract
5012 - Inhibition of the PI3K pathway in HER2-positive gastric cancer
Presenter: Sinead Toomey
Session: Poster Display session 2
Resources:
Abstract
4803 - Investigation on gastric cancer susceptibility genes in Chinese early-onset diffuse gastric cancer
Presenter: Yi Feng
Session: Poster Display session 2
Resources:
Abstract
4778 - A correlation analysis between survival rate and the characteristic gene of gastric cancer based on bioinformatics analysis
Presenter: Yi-wen Zhang
Session: Poster Display session 2
Resources:
Abstract
4805 - Phase I study of apatinib combined with POF (paclitaxel plus FOLFOX) in patients (pts) with treatment-naïve advanced gastric cancer (TNAGC)
Presenter: Rongbo LIN
Session: Poster Display session 2
Resources:
Abstract