sotorasib and Drug-Related-Side-Effects-and-Adverse-Reactions

Sequential anti-programmed cell death protein 1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) followed by small targeted therapy use is associated with increased prevalence of adverse events (AEs) in NSCLC. KRASG12C inhibitor sotorasib may trigger severe immune-mediated hepatotoxicity when used in sequence or in combination with anti-PD-(L)1. This study was designed to address whether sequential anti-PD-(L)1 and sotorasib therapy increases the risk of hepatotoxicity and other AEs.. This is a multicenter, retrospective study of consecutive advanced KRAS. We identified 102 patients who received sotorasib, including 48 (47%) in the sequence group and 54 (53%) in the control group. Patients in the control group received an anti-PD-(L)1 followed by at least one treatment regimen before sotorasib in 87% of the cases or did not receive an anti-PD-(L)1 at any time before sotorasib in 13% of the cases. Severe sotorasib-related AEs were significantly more frequent in the sequence group compared with those in the control group (50% versus 13%, p < 0.001). Severe sotorasib-related AEs occurred in 24 patients (24 of 48, 50%) in the sequence group, and among them 16 (67%) experienced a severe sotorasib-related hepatotoxicity. Severe sotorasib-related hepatotoxicity was threefold more frequent in the sequence group compared with that in the control group (33% versus 11%, p = 0.006). No fatal sotorasib-related hepatotoxicity was reported. Non-liver severe sotorasib-related AEs were significantly more frequent in the sequence group (27% versus 4%, p < 0.001). Severe sotorasib-related AEs typically occurred in patients who received last anti-PD-(L)1 infusion within 30 days before sotorasib initiation.. Sequential anti-PD-(L)1 and sotorasib therapy are associated with a significantly increased risk of severe sotorasib-related hepatotoxicity and severe non-liver AEs. We suggest avoiding starting sotorasib within 30 days from the last anti-PD-(L)1 infusion.

Topics: Antineoplastic Agents, Immunological; Carcinoma, Non-Small-Cell Lung; Cell Death; Chemical and Drug Induced Liver Injury; Drug-Related Side Effects and Adverse Reactions; Humans; Ligands; Lung Neoplasms; Proto-Oncogene Proteins p21(ras); Retrospective Studies

Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Immune Checkpoint Inhibitors; Maximum Tolerated Dose; Neoplasms; Piperazines; Pyridines; Pyrimidines; United States; United States Food and Drug Administration

Topics: Carcinoma, Non-Small-Cell Lung; Drug-Related Side Effects and Adverse Reactions; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Maximum Tolerated Dose; Piperazines; Pyridines; Pyrimidines; United States; United States Food and Drug Administration