37P Sotorasib-induced liver and non-liver toxicity associated with sequential sotorasib following anti-PD(L)1 in KRASG12C mutant lung cancer

Sotorasib is effective in KRASG12C mutant non-small cell lung cancer (KRASG12CNSCLC) and under investigation phase III trial. Targeted therapy anti-PD(L)1 sequence/combination associated with adverse event (AE) excess. We sought to describe sotorasib-related AE (SRAE) sequential sotorasib following anti-PD(L)1. Consecutive KRASG12CNSCLC treated outside clinical trial 16 French centers from January September 2021 were retrospectively enrolled. Anonymized clinical/pathologic features SRAE graded according the CTCAE5 classification collected. 102 pts 48 (45.1%) received as last treatment line before (IO-sequence group). Among remaining 54 pts, 83.3% an (non-IO-sequence Clinicopathological characteristics comparable IO- non-IO-sequence group. Median time between infusion initiation was 1.2 mo. (range 0-13.1) 7.4 2.3-51.2) group, respectively (p<0,05). Grade (G) 1 2 frequency similar both groups. 23.5% 6.86% of experienced at least one G?3 non-IO sequence 45 SRAE, including 31 liver toxicities (GGT/ALT/AST/Alk P/total bilirubinemia elevation), 12 7 toxicities, reported non-1O respectively. Two G5 (1 hepatitis, toxic epidermal necrolysis) occurred IO none were: GGT elevation, 8.8% vs. 2.9% (p<0.05); ALT 7.8% 1.96% (p<0,05); AST 6.9% (p=ns); Alk P 3.9% 0% total (2.94 0%, p=ns); Last given <90 days 81% (13/16) 71% (22/31) SR toxicity cases any cases, Sequential may be non-liver