Management of Adverse Reactions Related to Lenvatinib Plus Pembrolizumab Treatment Among Patients With Renal Cell Carcinoma.

Renal cell carcinoma is the predominant histological type of kidney cancer with historically poor patient outcomes. Lenvatinib in combination with pembrolizumab is an approved first-line regimen for people with advanced renal cell carcinoma that showed clinically meaningful improvements in efficacy over sunitinib in the CLEAR trial; however, reduced patient exposure to treatment (often stemming from adverse reactions) is a potential therapeutic barrier that must be addressed. Here, we present management strategies for adverse reactions associated with this treatment combination: fatigue, diarrhea, musculoskeletal pain, hypertension, stomatitis, decreased appetite, rash, nausea, and proteinuria. Dosing modification of lenvatinib and pembrolizumab should be made according to the prescribing information for each medication. Clinicians should consider that some adverse reactions, such as diarrhea, may be attributable to lenvatinib, or may be a symptom of immune-related adverse reactions to pembrolizumab (such as colitis). Adverse reactions can generally be managed by: (1) advising the patient on precautionary measures (eg, for stomatitis, practice dental hygiene, avoid irritating foods, and maintain adequate hydration), (2) monitoring for changes in symptoms from baseline (eg, changes in bowel movements, blood pressure or level of fatigue), (3) interrupting/dose reducing lenvatinib or interrupting pembrolizumab, if warranted, and advising the patient to manage their current symptoms via self-care (managing diarrhea with antidiarrheal agents and hydration), and (4) implementing medical interventions (eg, thyroid replacement or antihypertensive therapy) when needed. Through successful management of adverse reactions, oncology clinicians can improve the well-being of their patients and likely enhance adherence rates to treatment with lenvatinib and pembrolizumab.
Competing Interests: Disclosures Viktor Grünwald reports receiving stock and other ownership interests from AstraZeneca, Bristol Myers Squibb, MSD, and Seagen; honoraria from AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, EUSA Pharma, Ipsen, Janssen-Cilag, Lilly, Merck Serono, MSD Oncology, Novartis, Pfizer, PharmaMar, and Roche; has a consulting or advisory role for Bristol Myers Squibb, Ipsen, Janssen-Cilag, Lilly, MSD Oncology, Novartis, and Pfizer; has received research funding (inst) from Novartis; and has received travel/accommodations/expenses from AstraZeneca, Bayer, Bristol Myers Squibb, Ipsen, and Pfizer. James Larkin reports receiving honoraria from Eisai, Novartis, Incyte, Merck, touchIME, touchEXPERTS, Pfizer, Royal College of Physicians, Cambridge Healthcare Research, Royal College of General Practitioners, Ujoncology, Agence Unik, and BMS; a consulting or advisory role from iOnctura, Apple Tree, Merck, BMS, Eisai, Debipharm, and Incyte; institutional research funding from BMS, MSD, Novartis, Pfizer, Achilles, Roche, Nektar, Covance, Aveo, Immunocore, Pharmacylics; and travel, accommodations and expenses from Roche/Genentech, GlaxoSmithKline, and Pierre Fabre. Javier Puente reports receiving honoraria from Pfizer, Bristol Myers Squibb, Ipsen, AstraZeneca, Roche, MSD Oncology, Janssen-Cilag, Astellas Pharma, EUSA Pharma, Eisai, Pierre Fabre, Sanofi, and Bayer; a consulting or advisory role from Pfizer, Astellas Pharma, Janssen-Cilag, Merck Sharp & Dohme, Bayer, Roche, Bristol Myers Squibb, Clovis Oncology, Ipsen, Eisai, and Sanofi; research funding from Astellas Pharma and Pfizer; and travel accommodations and expenses from Pfizer, Roche, Janssen-Cilag, Bristol Myers Squibb, and MSD Oncology. Jens Bedke reports receiving institutional honoraria from BMS and MSD; personal honoraria from AstraZeneca, Astellas, BMS, Eisai, EUSA Pharma, Ipsen, MSD, Merck Serono, Novartis, Pfizer, and Roche; and institutional research funding from AstraZeneca, Astellas, BMS, Eisai, Ipsen, MSD, Novartis, Nektar, Pfizer, Roche, and Seattle Genetics. Camillo Porta reports receiving a consulting, advisory, and/or speaker role from Angelini Pharma, AstraZeneca, Bristol Myers Squibb, Eisai, Exelixis, Ipsen, Merck, and MSD Oncology; is a protocol steering committee member for BMS, Eisai, and MSD.
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