Skoulidis, FerdinandosFerdinandosSkoulidisLi, Bob TBob TLiHochmair, MaximilianMaximilianHochmairGovindan, RamaswamyRamaswamyGovindanVincent, MarkMarkVincentvan der Wekken, Anthonie JAnthonie Jvan der WekkenReguart Aransay, NoemiNoemiReguart AransayO'Byrne, Kenneth JKenneth JO'ByrneGirard, NicolasNicolasGirardGriesinger, FrankFrankGriesingerNishio, MakotoMakotoNishioHäfliger, SimonSimonHäfligerLindsay, ColinColinLindsayReinmuth, NielsNielsReinmuthPaulus, AstridAstridPaulusPapakotoulas, PavlosPavlosPapakotoulasKim, Sang-WeSang-WeKimFerreira, Carlos GilCarlos GilFerreiraPasello, GiuliaGiuliaPaselloDuruisseaux, MichaelMichaelDuruisseauxGennatas, SpyridonSpyridonGennatasDimou, AnastasiosAnastasiosDimouMehta, BhaktiBhaktiMehtaKormany, WilliamWilliamKormanyNduka, ChidozieChidozieNdukaSylvester, Brooke EBrooke ESylvesterArdito-Abraham, ChristineChristineArdito-AbrahamWang, YangYangWangde Langen, Adrianus JohannesAdrianus Johannesde Langen2025-02-062025-02-062025-01-17https://boris-portal.unibe.ch/handle/20.500.12422/203463Introduction 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.enKRAS G12Cmanagementnon-small cell lung cancerpooled analysissafetysotorasibtreatment-related adverse events600 - Technology::610 - Medicine & healtharticle10.48620/852303984698110.1093/oncolo/oyae356