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Response to immunotherapy in KRAS G12C mutated NSCLC: a single-centre retrospective observational study
Carolina Sciortino1, Valentina Viglialoro1, Massimo Nucci1
1Department of Radiology, Oncology and Pathology, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
Background:
Non-small cell lung cancer is the leading cause of cancer death worldwide. New strategies in molecular therapies are being explored to detect and target genetic mutations in NSCLC. Therefore, it is also important to understand the interaction between these mutations and other therapies. This study focuses on possible correlations between the KRAS-G12C mutation and response of patients treated with immunotherapy.
Methods:
Twenty-two patients with stage IV NSCLC undergoing immunotherapy were divided into two groups treated with first- and second-line therapy, respectively. KRAS-G12C mutation was detected by liquid biopsy Idylla KRAS assay.
Results:
In first-line treated patients, there was no significant increase in PFS in patients with the KRAS mutation (20 months versus 14.5 months, HR = 1.31; CI 95% = 0.25-6.71; p value = 0.76) and no difference in OS (OS = 21 months, HR = 1; CI 95% = 0.17-6.2; p value > 0.99). In the second group, KRAS G12C mutated patients had a median PFS of 23 months compared with a median PFS of only 5 months among nonmutated patients (HR = 3.28; CI 95% = 0.86-12.5; p value = 0.03).
Conclusion:
The results of this study do not reveal a clear correlation between mutation and response to immunotherapy. The mechanism regulating immune system activity in the tumor microenvironment remains unclear.
Insights
The KRAS-G12C mutation did not significantly impact immunotherapy response in first-line non-small cell lung cancer (NSCLC) patients. However, in second-line treatment, this mutation was associated with improved progression-free survival.
Area of Science:
- Oncology
- Molecular Biology
- Immunotherapy
Background:
- Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality globally.
- Targeting specific genetic mutations, like KRAS-G12C, is a key strategy in NSCLC molecular therapies.
- Understanding the interplay between KRAS-G12C mutations and immunotherapy is crucial for treatment optimization.
Purpose of the Study:
- To investigate the correlation between the KRAS-G12C mutation and patient response to immunotherapy in NSCLC.
- To analyze progression-free survival (PFS) and overall survival (OS) in relation to KRAS-G12C status in different lines of immunotherapy.
Main Methods:
- A cohort of 22 stage IV NSCLC patients receiving immunotherapy was studied.
- Patients were stratified into first- and second-line therapy groups.
- KRAS-G12C mutations were identified using liquid biopsy with the Idylla KRAS assay.
Main Results:
- In first-line therapy, no significant difference in PFS or OS was observed between KRAS-G12C mutated and non-mutated patients.
- In second-line therapy, patients with the KRAS-G12C mutation showed a median PFS of 23 months compared to 5 months for non-mutated patients (p=0.03).
Conclusions:
- The study did not establish a clear link between KRAS-G12C mutation and immunotherapy response across all treatment lines.
- The underlying mechanisms influencing immune activity in the tumor microenvironment in relation to this mutation require further investigation.
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