1. Practical Guidance for the Management of Adverse Events in Patients with KRASG12C-Mutated Non-Small Cell Lung Cancer Receiving Adagrasib
- Author
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Zhang, Jun, Johnson, Melissa, Barve, Minal, Bazhenova, Lyudmila, McCarthy, Marybeth, Schwartz, Rowena, Horvath-Walsh, Elise, Velastegui, Karen, Qian, Chunlin, and Spira, Alexander
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Research ,Clinical Trials and Supportive Activities ,Cancer ,Patient Safety ,Digestive Diseases ,Liver Disease ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Humans ,Carcinoma ,Non-Small-Cell Lung ,Lung Neoplasms ,Piperazines ,Acetonitriles ,KRASG12C mutation ,adagrasib ,adverse events ,management ,non-small cell lung cancer ,safety ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
Adagrasib (MRTX849) is a KRASG12C inhibitor with favorable properties, including long half-life (23 h), dose-dependent pharmacokinetics, and central nervous system (CNS) penetration. As of September 1, 2022, a total of 853 patients with KRASG12C-mutated solid tumors, including patients with CNS metastases, had received adagrasib (monotherapy or in combination). Adagrasib-related treatment-related adverse events (TRAEs) are generally mild to moderate in severity, start early in treatment, resolve quickly with appropriate intervention, and result in a low rate of treatment discontinuation. Common TRAEs seen in clinical trials included gastrointestinal-related toxicities (diarrhea, nausea, and vomiting); hepatic toxicities (increased alanine aminotransferase/aspartate aminotransferase) and fatigue, which can be managed through dose modifications, dietary modifications, concomitant medications (such as anti-diarrheals and anti-emetics/anti-nauseants) and the monitoring of liver enzymes and electrolytes. To manage common TRAEs effectively, it is imperative that clinicians are informed, and patients are fully counseled on management recommendations at treatment initiation. In this review, we provide practical guidance on the management of adagrasib TRAEs and discuss some best practices for patient and caregiver counseling to facilitate optimal outcomes for patients. Safety and tolerability data from the phase II cohort of the KRYSTAL-1 study will be reviewed and presented with practical management recommendations based on our experience as clinical investigators.
- Published
- 2023