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Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer

Skoulidis, F.
; 
Li, B. T.
; 
Hochmair, M.
; 
Govindan, R.
; 
Vincent, M.
; 
van der Wekken, A. J.
; 
Reguart Aransay, N.
; 
O'Byrne, K. J.
; 
Girard, N.
; 
Griesinger, F.
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Abstract
INTRODUCTION: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks. METHODS: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0. Adverse events were deemed sotorasib-related per investigator causality assessment. RESULTS: In the pooled population (n = 549), TRAEs were reported in 388 (70.7%) patients (grade 1: 124 [22.6%]; grade 2: 117 [21.3%]; grade ≥ 3: 147 [26.8%]). Gastrointestinal and hepatic TRAEs, including diarrhea (171 [31.1%]), nausea (80 [14.6%]), elevated alanine aminotransferase (ALT; 68 [12.4%]), and elevated aspartate aminotransferase (AST; 67 [12.2%]) were the most common (≥10%). Dose interruption and dose reduction of sotorasib resulted in the resolution of >90% of diarrhea events; median time to resolution were 18.0 days and 22.0 days, respectively. Similar trends were observed for elevated ALT and AST events. Patients who stopped immunotherapy <3 months before initiating sotorasib had a higher incidence of treatment-related hepatotoxicity (80/240 [33.3%]) than those who stopped immunotherapy ≥3 months before initiating sotorasib (26/188 [13.8%]). Treatment-related pneumonitis/interstitial lung disease (ILD) and corrected QT (QTc) prolongation were observed in 9 (1.6%) and 4 (0.7%) patients, respectively. Two (0.4%) patients died with TRAEs, 1 with ILD whose ultimate cause of death was disease progression, and the other with an unknown cause. CONCLUSIONS: Sotorasib has a well-characterized safety profile in patients with KRAS G12C-mutated advanced NSCLC, and key risks are manageable with dose modification.
Authors
Skoulidis, F.
Li, B. T.
Hochmair, M.
Govindan, R.
Vincent, M.
van der Wekken, A. J.
Reguart Aransay, N.
O'Byrne, K. J.
Girard, N.
Griesinger, F.
Nishio, M.
Häfliger, S.
Lindsay, C.
Reinmuth, N.
Paulus, A.
Papakotoulas, P.
Kim, S. W.
Ferreira, C. G.
Pasello, G.
Duruisseaux, M.
Gennatas, S.
Dimou, A.
Mehta, B.
Kormany, W.
Nduka, C.
Sylvester, B. E.
Ardito-Abraham, C.
Wang, Y.
de Langen, A. J.
Affiliation
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States. Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States. Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik Floridsdorf, 1210 Vienna, Austria. Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States. London Health Sciences Centre, Victoria Hospital, London, ON N6A 5W9, Canada. Department of Pulmonary Diseases and Tuberculosis, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, the Netherlands. Medical Oncology Department, Thoracic Oncology Unit Hospital Clinic, IDIBAPS, University of Barcelona, Villarroel, 08036 Barcelona, Spain. Faculty of Health, Queensland University of Technology, Brisbane, QLD 4000, Australia. Institut du Thorax Curie-Montsouris, Institut Curie, 75014 Paris, France. Pius-Hospital Oldenburg, Department of Haematology and Oncology, University Department Internal Medicine-Oncology, University Medicine Oldenburg, 26121 Oldenburg, Germany. Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan. Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland. Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, United Kingdom. The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom. Department of Oncology, Asklepios Lung Clinic, German Center for Lung Research, Munich-Gauting, 82131 Gauting, Germany. Department of Respiratory Medicine, University Hospital (CHU) of Liège, 4000 Liège, Belgium. First Department of Clinical Oncology, Theageneio Cancer Hospital, 54639 Thessaloniki, Macedonia, Greece. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea. Oncoclinicas, Rio De Janeiro, RJ, 22251-060, Brazil. Dipartimento di Scienze Chirurgiche, Oncologichee Gastroenterologiche (DiSCOG) dell'Università di Padova, Oncologia 2, Istituto Oncologico Veneto IRCCS, 64 Padova, Italy. Department of Medical Oncology, CHU de Lyon - Hôpital Lyon Sud, 69495 Lyon, France. Department of Medical Oncology, Guy's and St Thomas' NHS Foundation Trust, London SE1 7EH, United Kingdom. Department of Oncology, Mayo Clinic, Rochester, MN 55905, United States. Amgen Inc., Thousand Oaks, CA 91320, United States. Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Thoracic Oncology, 1066 CX Amsterdam, The Netherlands.
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2025
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All Christie Publications
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Citation
Skoulidis F, Li BT, Hochmair M, Govindan R, Vincent M, van der Wekken AJ, et al. Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer. Oncologist. 2025 Jan 17;30(1). PubMed PMID: 39846981. Pubmed Central PMCID: PMC11756274. Epub 2025/01/23. eng.
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https://christie.openrepository.com/handle/10541/627996
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