Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer Journal Article
| Authors: | Skoulidis, F.; Li, B. T.; Hochmair, M.; Govindan, R.; Vincent, M.; van der Wekken, A. J.; Aransay, N. R.; 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. |
| Article Title: | Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer |
| 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. © The Author(s) 2025. |
| Keywords: | adult; aged; aged, 80 and over; middle aged; genetics; mutation; drug tolerability; fatigue; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; monotherapy; pyridines; follow up; progression free survival; liver toxicity; phase 2 clinical trial; nausea; vomiting; carcinoma, non-small-cell lung; lung neoplasms; olanzapine; qt prolongation; pathology; pyrimidines; pneumonia; lung tumor; alanine aminotransferase; aspartate aminotransferase; ondansetron; interstitial lung disease; safety; loperamide; hormonal therapy; phase 3 clinical trial; phase 1 clinical trial; piperazines; corticosteroid; drug therapy; piperazine derivative; pyrimidine derivative; protein p21; proto-oncogene proteins p21(ras); management; prochlorperazine; non-small cell lung cancer; disease exacerbation; kras protein, human; pyridine derivative; antidiarrheal agent; programmed death 1 receptor; non small cell lung cancer; drug-induced liver injury; pooled analysis; dopamine receptor blocking agent; very elderly; humans; human; male; female; article; treatment-related adverse events; kras g12c; sotorasib; kras g12c-mutated advanced non-small cell lung cancer |
| Journal Title: | The Oncologist |
| Volume: | 30 |
| Issue: | 1 |
| ISSN: | 1083-7159 |
| Publisher: | Oxford University Press |
| Date Published: | 2025-01-01 |
| Start Page: | oyae356 |
| Language: | English |
| DOI: | 10.1093/oncolo/oyae356 |
| PUBMED: | 39846981 |
| PROVIDER: | scopus |
| PMCID: | PMC11756274 |
| DOI/URL: | |
| Notes: | Source: Scopus |
