Abstract 37P
Background
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.
Methods
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.
Results
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.
Conclusions
Sequential sotorasib following anti-PD(L)1 may be associated with G≥3 SR liver and non-liver toxicity excess.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Mascaux: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Kephren; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Kephren; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Other, Travel grant: Roche; Financial Interests, Personal, Other, Travel grant: AstraZeneca; Financial Interests, Personal, Other, Travel grant: Boehringer Ingelheim; Financial Interests, Personal, Other, Travel grant: Bristol Myers Squibb. A. Swalduz: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: AztraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer-Ingelheim; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Takeda. M. Darrason: Financial Interests, Personal, Other, Personal fees: Bristol Meyers Squibb; Financial Interests, Personal, Other, Personal fees: CCC Congres Colloques Conventions. J. Cadranel: Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: AztraZeneca; Financial Interests, Personal, Advisory Board: BI; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Institutional, Research Grant: AztraZeneca; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Sanofi. E. Auclin: Financial Interests, Personal, Other, Travel Grant: Mundipharma; Financial Interests, Personal, Training: Sanofi Genzymes; Financial Interests, Personal, Training: Lilly Oncology; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Sanofi Genzymes. C. Decroisette: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Aztra Zeneca; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Sandoz. E. Giroux-Leprieur: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer-Ingelheim; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Oncodesign; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Bristo-Myers-Squibb; Financial Interests, Institutional, Research Grant: Roche. M. Duruisseaux: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Guardant; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Institutional, Research Grant: Blueprint; Financial Interests, Institutional, Research Grant: Nanostring; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb. All other authors have declared no conflicts of interest.