Ferreira, Carlos Gil
Mayo Clinic
Oncoclinicas , Rio De Janeiro, RJ, 22251-060 ,
Citations 1
Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer
Skoulidis, Ferdinandos , Govindan, Ramaswamy , Vincent, Mark , Wekken, Anthonie J. van der , Aransay, N. Reguart, O’Byrne, Kenneth J. , Girard, Nicolas , Griesinger, Frank , Nishio, Makoto , Häfliger, Simon, Lindsay, Colin R. , Paulus, Astrid, Papakotoulas, Pavlos, Kim, Sang‐We , Gennatas, Spyridon , Mehta, Bhakti, Kormany, William, Sylvester, Brooke E., Ardito-Abraham, Christine , Langen, Adrianus J. de , Girard, Nicolas , Pasello, Giulia , de Langen, Adrianus Johannes , van der Wekken, Anthonie J , Govindan, Ramaswamy , Li, Bob T. , Hochmair, Maximilian Johannes , Haefliger, Simon , Reinmuth, Niels , Ferreira, Carlos Gil , Duruisseaux, M. , Dimou, Anastasios , Nduka, Chidozie U , Wang, Yang
The Oncologist | January 23, 2025 | Volume: 30 | Issue: 1 | Pages: No page available
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.