TY - JOUR
T1 - Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer
AU - Skoulidis, Ferdinandos
AU - Li, Bob T.
AU - Hochmair, Maximilian
AU - Govindan, Ramaswamy
AU - Vincent, Mark
AU - van der Wekken, Anthonie J.
AU - Aransay, Noemi Reguart
AU - O’Byrne, Kenneth J.
AU - Girard, Nicolas
AU - Griesinger, Frank
AU - Nishio, Makoto
AU - Häfliger, Simon
AU - Lindsay, Colin
AU - Reinmuth, Niels
AU - Paulus, Astrid
AU - Papakotoulas, Pavlos
AU - Kim, Sang We
AU - Ferreira, Carlos Gil
AU - Pasello, Giulia
AU - Duruisseaux, Michael
AU - Gennatas, Spyridon
AU - Dimou, Anastasios
AU - Mehta, Bhakti
AU - Kormany, William
AU - Nduka, Chidozie
AU - Sylvester, Brooke E.
AU - Ardito-Abraham, Christine
AU - Wang, Yang
AU - de Langen, Adrianus Johannes
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/1/1
Y1 - 2025/1/1
N2 - 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.
AB - 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.
KW - KRAS G12C
KW - management
KW - non-small cell lung cancer
KW - pooled analysis
KW - safety
KW - sotorasib
KW - treatment-related adverse events
UR - http://www.scopus.com/inward/record.url?scp=85216361470&partnerID=8YFLogxK
U2 - 10.1093/oncolo/oyae356
DO - 10.1093/oncolo/oyae356
M3 - Article
C2 - 39846981
AN - SCOPUS:85216361470
SN - 1083-7159
VL - 30
JO - Oncologist
JF - Oncologist
IS - 1
M1 - oyae356
ER -