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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Sotorasib in KRAS G12C-mutated non-small cell lung cancer: A multicenter real-world experience from the compassionate
Jan A Stratmann1, Friederike C Althoff1, Paula Doebel1
1Goethe University Frankfurt, University Hospital, Department of Internal Medicine II, Hematology/Oncology, Frankfurt am Main, 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. First response rates were promising in the CodeBreaK trials. It remains unclear whether response to sotorasib and outcomes differ in a real-world setting when including patients underrepresented in clinical trials.
Methods:
Patients with KRAS p.G12C-mutated advanced or metastatic NSCLC received sotorasib within the German multicenter sotorasib compassionate use program between 2020 to 2022. Data on efficacy, tolerability, and survival were analyzed in the full cohort and in subgroups of special interest such as co-occurring mutations and across PD-L1 expression levels.
Results:
We analyzed 163 patients who received sotorasib after a median of two treatment lines (range, 0 to 7). Every fourth patient had a poor performance status and 38% had brain metastases (BM). The objective response rate was 38.7%. The median overall survival was 9.8 months (95% CI, 6.5 to not reached). Median real-world (rw) progression-free survival was 4.8 months (9% CI, 3.9 to 5.9). Dose reductions and permanent discontinuation were necessary in 35 (21.5%) and 7 (4.3%) patients, respectively. Efficacy seems to be influenced by PD-L1 expression and a co-occurring KEAP1 mutation. KEAP1 was associated with an inferior survival. Other factors such as BM, STK11, and TP53 mutations had no impact on response and survival.
Conclusion:
First results from a real-world population confirm promising efficacy of sotorasib for the treatment of advanced KRAS p.G12C-mutated NSCLC. Patients with co-occurring KEAP1 mutations seem to derive less benefit.
Insights
Sotorasib shows promising efficacy in real-world KRAS G12C-mutated non-small cell lung cancer (NSCLC) patients. However, co-occurring KEAP1 mutations may reduce treatment benefit, impacting survival outcomes.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Sotorasib is a novel KRAS p.G12C-inhibitor approved for pretreated non-small cell lung cancer (NSCLC).
- Clinical trial data (CodeBreaK) indicated promising initial response rates.
- Real-world data are needed to assess efficacy and outcomes in diverse patient populations, including those underrepresented in trials.
Purpose of the Study:
- To evaluate the efficacy and tolerability of sotorasib in a real-world setting for advanced KRAS p.G12C-mutated NSCLC.
- To identify factors influencing treatment response and survival, including co-occurring mutations and PD-L1 expression.
- To compare real-world outcomes with clinical trial findings.
Main Methods:
- Retrospective analysis of 163 patients with KRAS p.G12C-mutated advanced or metastatic NSCLC treated with sotorasib.
- Data collected through the German multicenter sotorasib compassionate use program (2020-2022).
- Analysis of efficacy, tolerability, survival, and impact of co-occurring mutations (KEAP1, STK11, TP53) and PD-L1 expression.
Main Results:
- Objective response rate was 38.7% in 163 patients, with a median overall survival of 9.8 months.
- Median real-world progression-free survival was 4.8 months; 21.5% required dose reductions.
- KEAP1 co-mutation was associated with inferior survival, while brain metastases and other mutations (STK11, TP53) had no significant impact.
Conclusions:
- Real-world data confirm sotorasib's promising efficacy in advanced KRAS p.G12C-mutated NSCLC.
- Patients with co-occurring KEAP1 mutations appear to benefit less from sotorasib treatment.
- Further research is warranted to optimize treatment strategies for NSCLC patients with specific genetic profiles.
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