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

Abstract

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