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
3536 - Palbociclib plus an aromatase inhibitor as first-line therapy for metastatic breast cancer in US clinical practices: Real-world progression-free survival analysis
Presenter: Mylin Torres
Session: Poster Display session 2
Resources:
Abstract
4022 - Ribociclib (RIB) plus letrozole (LET) in male patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC) from the CompLEEment-1 trial
Presenter: Mario Campone
Session: Poster Display session 2
Resources:
Abstract
3599 - Comparative effectiveness of palbociclib plus letrozole vs letrozole for metastatic breast cancer in US real-world clinical practices
Presenter: Rachel Layman
Session: Poster Display session 2
Resources:
Abstract
901 - Pharmacokinetics (PK), safety, and efficacy of [fam-] trastuzumab deruxtecan with OATP1B/CYP3A inhibitors in subjects with HER2-expressing advanced solid tumors
Presenter: Yung-Jue Bang
Session: Poster Display session 2
Resources:
Abstract
2777 - A Phase 2 study of abemaciclib in patients (pts) with brain metastases (BM) secondary to non-small cell lung cancer (NSCLC) or melanoma (MEL).
Presenter: Solmaz Sahebjam
Session: Poster Display session 2
Resources:
Abstract
3980 - Ribociclib (RIB) + letrozole (LET) in patients (pts) with visceral metastases (VM) or bone-only metastases (BOM) in hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC): Subgroup analysis from the CompLEEment-1 trial
Presenter: Michelino De Laurentiis
Session: Poster Display session 2
Resources:
Abstract
4024 - Ribociclib (RIB) + letrozole (LET) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC) and central nervous system (CNS) metastases: Subgroup analysis from the phase 3b CompLEEment-1 trial
Presenter: Paul Cottu
Session: Poster Display session 2
Resources:
Abstract
2151 - Clinical outcome and toxicity data in patients with advanced breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy in a real-world clinical setting.
Presenter: Elena Fountzilas
Session: Poster Display session 2
Resources:
Abstract
3994 - Safety and efficacy of Ribociclib (RIBO) + letrozole (LET) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC): Interim results from the Italian cohort of the CompLEEment-1 (C-1) study.
Presenter: Michele De Laurentiis
Session: Poster Display session 2
Resources:
Abstract
1370 - Interim Results From CompLEEment-1 (A Phase 3b Study of Ribociclib and Letrozole as First-Line Therapy for Advanced Breast Cancer in an Expanded Population): Spanish cohort results
Presenter: Javier Salvador
Session: Poster Display session 2
Resources:
Abstract