Characterization and Management of Adverse Reactions in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab.

adverse reactions endometrial cancer lenvatinib pembrolizumab

Journal

The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837

Informations de publication

Date de publication:
31 Jul 2023
Historique:
received: 26 10 2022
accepted: 19 06 2023
medline: 31 7 2023
pubmed: 31 7 2023
entrez: 31 7 2023
Statut: aheadofprint

Résumé

Lenvatinib plus pembrolizumab significantly improved efficacy compared with chemotherapy in patients with advanced endometrial cancer (aEC) regardless of microsatellite instability status or histologic subtype, who had disease progression following prior platinum-based therapy, in Study-309/KEYNOTE-775. The safety profile of the combination was generally consistent with that of each monotherapy drug and of the combination in patients with endometrial cancer and other solid tumors. Given the medical complexity of patients with aEC, this paper aims to characterize key adverse reactions (ARs) of the combination treatment and review management strategies, providing a guide for AR management to maximize anticancer benefits and minimize treatment discontinuation. In Study-309/KEYNOTE-775, patients received lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously every 3 weeks) or chemotherapy (doxorubicin or paclitaxel). The incidence and median time to the first onset of ARs, dose modifications, and concomitant medications are described. Key ARs characterized include hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight decreased, proteinuria, and palmar-plantar erythrodysesthesia syndrome. As expected, the most common any-grade key ARs included: hypothyroidism, hypertension, fatigue, diarrhea, and musculoskeletal disorders. Grades 3-4 key ARs with incidence ≥10% included: hypertension, fatigue, and weight decreased. Key ARs first occurred within approximately 3 months of treatment initiation. AR management strategies consistent with the prescribing information and the study protocol are discussed. Successful AR management strategies for lenvatinib plus pembrolizumab include education of the patient and entire treatment team, preventative measures and close monitoring, and judicious use of dose modifications and concomitant medications. NCT03517449.

Sections du résumé

BACKGROUND BACKGROUND
Lenvatinib plus pembrolizumab significantly improved efficacy compared with chemotherapy in patients with advanced endometrial cancer (aEC) regardless of microsatellite instability status or histologic subtype, who had disease progression following prior platinum-based therapy, in Study-309/KEYNOTE-775. The safety profile of the combination was generally consistent with that of each monotherapy drug and of the combination in patients with endometrial cancer and other solid tumors. Given the medical complexity of patients with aEC, this paper aims to characterize key adverse reactions (ARs) of the combination treatment and review management strategies, providing a guide for AR management to maximize anticancer benefits and minimize treatment discontinuation.
MATERIALS AND METHODS METHODS
In Study-309/KEYNOTE-775, patients received lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously every 3 weeks) or chemotherapy (doxorubicin or paclitaxel). The incidence and median time to the first onset of ARs, dose modifications, and concomitant medications are described. Key ARs characterized include hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight decreased, proteinuria, and palmar-plantar erythrodysesthesia syndrome.
RESULTS RESULTS
As expected, the most common any-grade key ARs included: hypothyroidism, hypertension, fatigue, diarrhea, and musculoskeletal disorders. Grades 3-4 key ARs with incidence ≥10% included: hypertension, fatigue, and weight decreased. Key ARs first occurred within approximately 3 months of treatment initiation. AR management strategies consistent with the prescribing information and the study protocol are discussed.
CONCLUSION CONCLUSIONS
Successful AR management strategies for lenvatinib plus pembrolizumab include education of the patient and entire treatment team, preventative measures and close monitoring, and judicious use of dose modifications and concomitant medications.
CLINICALTRIALS.GOV ID BACKGROUND
NCT03517449.

Identifiants

pubmed: 37523661
pii: 7234211
doi: 10.1093/oncolo/oyad201
pii:
doi:

Banques de données

ClinicalTrials.gov
['NCT03517449']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press.

Auteurs

Nicoletta Colombo (N)

Gynecologic Oncology Department, European Institute of Oncology IRCCS, Milan, Italy.
Department of Medicine and Surgery, University of Milan-Bicocca, Italy.

Domenica Lorusso (D)

Division of Gynecologic Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy.

Bradley J Monk (BJ)

HonorHealth Research Institute, University of Arizona, Creighton University, Phoenix, AZ, USA.

Brian Slomovitz (B)

Division of Gynecologic Oncology, Mount Sinai Medical Center, Miami Beach, FL, USA.

Kosei Hasegawa (K)

Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan.

Angélica Nogueira-Rodrigues (A)

Universidade Federal de Minas Gerais (UFMG), Brazilian Group of Gynecologic Oncology (EVA), Grupo Oncoclínicas, DOM Oncologia, Brazil.

Melissa Zale (M)

Clinical Safety & Risk Management Late-Stage Oncology - Gynecologic Cancers, Merck & Co., Inc., Rahway, NJ, USA.

Chinyere E Okpara (CE)

Clinical Research, Eisai Ltd., Hatfield, UK.

Gianmaria Barresi (G)

Merck & Co., Inc., Switzerland.

Jodi McKenzie (J)

Oncology Business Group, Eisai Inc., Nutley, NJ, USA.

Vicky Makker (V)

Department of Medicine, Memorial Sloan Kettering Cancer Center; Weill Cornell Medical Center, New York, NY, USA.

Classifications MeSH