1400P - Real-world effectiveness and safety of sotorasib in patients with KRAS G12C mutated metastatic non-small cell lung cancer (NSCLC): Results of the IFCT-2102 Lung KG12Ci study

Background

Sotorasib has demonstrated robust activity in phase 3 trial in pretreated NSCLC patients (pts) with KRAS G12C mutation. However, its effectiveness and safety in a real-world (RW) setting, particularly when administered after treatment with immune checkpoint inhibitors (ICI), remains to be confirmed.

Methods

Multicenter retrospective study including NSCLC pts who received at least one dose of sotorasib as part of the French expanded access program between February 2021 and April 2022. The primary objective was to evaluate real-world progression-free survival (rwPFS), and the secondary objectives included overall survival (OS) and reporting of sotorasib-related hepatic toxicity.

Results

At time of intermediate database lock a total of 313 pts with data collection completed (out of 446 included) were considered in this analysis. At time of sotorasib initiation: median age 66 years (range [39-85]), males (56%), PS2+ (30%) and smokers (95%). Brain metastases (BM) were present in 116 (37%) pts, with 53% in progression. PD-L1 expression was < 1% in 33%, ≥ 1-49% in 35% and ≥ 50% in 23% of the pts. The median number of lines of treatment before sotorasib was 2.0, and the last treatment before sotorasib included ICI in 164 pts. The median follow-up time was 13.7 months (ms). Median rwPFS was 4.2 ms [95%CI 3.3;4.9], and median OS was 9.3 ms [95%CI 7.9 ;12.3]. Objective response rate (ORR) was 34.3% [95%CI 28.4; 40.1] and disease control rate (DCR) was 64.2%. Median duration of response was 3.9 ms [95%CI 2.9;5.6]. In BM, DCR was 65.9% with 18.7% of ORR. Hepatic grade 3 or 4 treatment-related adverse events (TRAEs) were reported in 7% pts, with ALAT elevation observed in 3.5% and ASAT elevation observed in 2.2% of pts. Among 263 pts who stopped treatment, 42 (16%) discontinued sotorasib due to toxicity, including hepatic toxicity (26 pts), diarrhea (14 pts) and other reasons (8 pts).

Conclusions

Our IFCT-2102 study confirms the effectiveness of sotorasib in pretreated KRAS G12C-NSCLC pts, and its safety profile is manageable with hepatic grade 3 or 4 TRAEs occurring in 7% of pts. Our findings support the use of sotorasib as a treatment option in this population.

Clinical trial identification

NCT05273047.

Editorial acknowledgement

Legal entity responsible for the study

IFCT.

Funding

Amgen.

Disclosure

M. Wislez: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, Roche, BMS, MSD, AstraZeneca, Sanofi, Novartis, Lilly; Financial Interests, Personal, Speaker’s Bureau: Amgen, MSD, BMS, AstraZeneca, Lilly, Sanofi; Non-Financial Interests, Personal, Non financial benefits, Support for attending meetings and/or travel: Roche, MSD. C. Mascaux: Financial Interests, Personal, Speaker, Consultant, Advisor: GSK, Janssen, Amgen, Kephren, AstraZeneca, MSD, Bristol Myers Squibb, Pfizer, Takeda, Sanofi, Roche, Amgen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD; Financial Interests, Personal, Other, Uncompensated Relationships: Boehringer Ingelheim. J. Cadranel: Financial Interests, Personal, Advisory Board, Participation to boards: Amgen, Daiichi, Takeda, MSD, Jansen, AZ; Financial Interests, Institutional, Other, prospective: AbbVie; Non-Financial Interests, Principal Investigator, Trials: AZ, AbbVie, Takeda, BI, Daiichi, Pfizer, Novartis, Amgen, Sanofi, Janssen, BMS; Financial Interests, Institutional, Research Grant, Translational research: AbbVie; Financial Interests, Institutional, Research Grant, Preclinical research: Sanofi; Financial Interests, Institutional, Research Grant, Support to academic trial: Pfizer; Financial Interests, Personal, Advisory Board, Participation to Boards: Pfizer; Financial Interests, Institutional, Advisory Board, Participation to boards: Novartis, Sanofi; Financial Interests, Personal, Invited Speaker, Participation to boards: BI. Q. Thomas: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, Sanofi, AstraZeneca; Non-Financial Interests, Personal, Non financial benefits, Support for attending meetings and/or travel: Sanofi. A. Swalduz: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Janssen, Roche, Amgen, BMS, Pfizer, Lilly. E. Pichon: Non-Financial Interests, Personal, Non financial benefits, Attending meeting: Takeda; Financial Interests, Personal, Other, Personal payment for educational event: Takeda; Financial Interests, Institutional, Local PI, clinical trials: BeiGene, AstraZeneca, Bristol Myers Squib, Janssen. V. Gounant: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, Takeda; Non-Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Sanofi, Pfizer. G. Rousseau Bussac: Financial Interests, Institutional, Research Grant: Takeda, AstraZeneca, BMS; Financial Interests, Personal, Speaker’s Bureau: BMS, Takeda; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Sanofi, Boehringer, AstraZeneca. A. Madroszyk Flandin: Financial Interests, Institutional, Research Grant: AstraZeneca, Roche; Financial Interests, Personal, Expert Testimony: AstraZeneca, Roche; Non-Financial Interests, Personal, Non financial benefits, Support for attending meetings and/or travel: AstraZeneca, Pfizer. C. Daniel: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, MSD, Amgen, Sanofi. P. Fournel: Financial Interests, Personal, Advisory Board: BMS, Sanofi, Janssen; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Amgen; Financial Interests, Personal, Other, Congress invitation: Takeda; Financial Interests, Institutional, Local PI: BMS, Ipsen. F. Guisier: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, MSD, Roche, Sanofi, Janssen, Pfizer, Takeda; Financial Interests, Institutional, Research Grant: Pfizer, Roche, Takeda. V. Westeel: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting fees: Amgen; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Bristol Myers Squibb, MSD, Roche, Sanofi; Non-Financial Interests, Personal, Other, Support for attending meetings and/or travel: AstraZeneca, Bristol Myers Squibb, Janssen, MSD, Roche, Sanofi; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Ipsen. All other authors have declared no conflicts of interest.