1405P - Sotorasib in KRAS G12C-mutated NSCLC: A multicenter real-world experience from the expanded access program in Germany

Background

Sotorasib is a first-in-class KRAS p.G12C-inhibitor that has entered clinical trials in pretreated patients with non-small cell lung cancer (NSCLC) in 2018. It remains unclear whether response to sotorasib and outcomes differ in a real-world setting when including patients of higher risk.

Methods

Patients with KRAS p.G12C-mutated advanced or metastatic NSCLC received sotorasib within the German multicenter sotorasib expanded access program between April 2021 to February 2022. Data on effectiveness, tolerability, and survival were analyzed in the full cohort and in subgroups of special interest such as patients with co-occurring mutations and across PD-L1 expression levels.

Results

We analyzed 173 patients who received sotorasib after a median of 2 previous treatment lines (range, 0 to 7). Every fourth patient had a poor performance status and 38% had brain metastases (BM) at the time of sotorasib initiation. The objective response rate was 38.7%. The median overall survival was 9.8 months (95% CI, 6.5 to not reached), with a 1-year mortality rate of 48.5%. Response to sotorasib was lower among patients with a positive PD-L1 expression (TPS ≥1%) and a co-occurring KEAP1 mutation, respectively. Patients with KEAP1 had a higher risk of 1-year real-world disease progression (HR 2.0, 0.9 to 4.2, p=0.01). Patients with poor performance status had significantly inferior 1-year overall survival (HR 2.2 ,95% CI 1.12 to 4.54, p=0.003). Other patient factors such as BM, STK11, and TP53 mutations had no impact on response and survival. Subgroup analysis indicated an intracranial non-progression rate of 74.5%, with an intracranial real-world progression-free survival of 7.5 months (95% CI 3.7 to 11.4). Dose reductions and permanent discontinuation were necessary in 35 (21.5%) and 7 (4.3%) patients, respectively, mostly due to gastrointestinal toxicity including liver enzyme elevation, irrespective of whether the immediate previous treatment line contained a checkpoint inhibitor or not.

Conclusions

These first results from a real-world population in Germany confirm promising effectiveness of sotorasib for the treatment of advanced KRAS p.G12C-mutated NSCLC. Patients with co-occurring KEAP1 mutation seem to derive less benefit.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

There was no funding; the work was non-financially supported by Amgen, Germany.

Disclosure

J.A. Stratmann: Financial Interests, Personal, Speaker, Consultant, Advisor: Boehringer Ingelheim, AstraZeneca, Roche, BMS, Amgen, Leo Pharma, Novartis. N. Frost: Financial Interests, Personal, Speaker, Consultant, Advisor, outside of the submitted work: AbbVie, Amgen, AstraZeneca, BeiGene, Berlin Chemie, Boehringer Ingelheim, BMS, Lilly, Merck, Merck Sharp&Dohme, Novartis, Pfizer, Roche, Sanofi, Takeda. P. Christopoulos: Financial Interests, Personal, Speaker, Consultant, Advisor, outside the submitted work: AstraZeneca, Amgen, Boehringer Ingelheim, Novartis, Roche, Takeda, Lilly, Daiichi Sankyo, Gilead, Novartis, Pfizer, Chugai, MSD. S. Kaldune: Financial Interests, Personal, Speaker, Consultant, Advisor, outside of the submitted work: Roche, Boehringer Ingelheim, MSD, Celgene. C. Schumann: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Roche; Financial Interests, Personal, Writing Engagement: AstraZeneca; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: BMS, MSD; Financial Interests, Institutional, Invited Speaker: Lilly. F. Griesinger: Financial Interests, Personal, Speaker, Consultant, Advisor, outside of the submitted work: AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Siemens, Amgen, Ariad, AbbVie, Tesaro / GSK, Sanofi, Daiichi Sankyo, BeiGene. M. Sebastian: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, BMS, Roche, Novartis, Sanofi, Takeda, Boehringer Ingelheim, AstraZeneca, MSD, AbbVie, Pfizer, Celgene, BioNTech, CureVac, Novartis, Janssen, Tesaro. N. Reinmuth: Financial Interests, Personal, Speaker, Consultant, Advisor, outside the submitted work.: Amgen, AstraZeneca, BMS, GSK, Hoffmann-La Roche, Janssen, MSD, Merck, Lilly, Takeda, Pfizer, Daiichi Sankyo; Financial Interests, Personal, Speaker, Consultant, Advisor, outside the submitted work: Boehringer Ingelheim. All other authors have declared no conflicts of interest.