The Activity of Immune Checkpoint Inhibition in KRAS Mutated Non-small Cell Lung Cancer: A Single Centre Experience
Javier Torralvo1, Alex Friedlaender1, Verane Achard2
1Oncology Department, Geneva University Hospital, Geneva, Switzerland.
Background/Aim:
KRAS mutation is the most frequent molecular alteration found in advanced non-small cell lung cancer (NSCLC). It is associated with a poor prognosis without available targeted therapy. Treatment options for NSCLC have been recently enriched by the development of immune checkpoint inhibitors (ICIs), and data about their efficacy in patients with KRAS-mutant NSCLC are discordant. This study assessed the routine efficacy of ICIs in advanced KRAS-mutant NSCLC.
Patients And Methods:
All stage IV NSCLC patients treated in our institution from January 2016 to December 2017 with immunotherapy were included in our analysis. We collected the status of KRAS and other mutations, as well as the type of ICI administered. We assessed four clinical outcomes: i) disease control rate (DCR), ii) partial response (PR), iii) progression-free survival (PFS) and iv) overall survival (OS).
Results:
A total of 45 patients were initially identified but 7 were excluded due to insufficient clinical data, so 38 were included in the end. In the KRAS wild-type cohort, the DCR was 59% with 49% PR, while the PFS was 8.4 months and OS 16.8 months. Among KRAS mutated patients, results were more favourable, the DCR was 81%, with 62% PR. PFS was 13.6 months and OS was 18.5 months. The median follow-up was 24 months (17 to 34 months) and 7 patients were still on treatment at the time of analysis.
Conclusion:
Our data suggest that KRAS mutation is predictive of a superior response to immunotherapy. Furthermore, the lack of response of STK11 and KRAS co-mutated NSCLC patients to ICIs, is indeed negated by an additional TP53 mutation.
Insights
KRAS mutations in advanced non-small cell lung cancer (NSCLC) patients show a better response to immune checkpoint inhibitors (ICIs). This suggests KRAS mutation status can predict immunotherapy effectiveness in NSCLC.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Diagnostics
Background:
- KRAS mutations are common in advanced non-small cell lung cancer (NSCLC) and historically linked to poor outcomes.
- Immune checkpoint inhibitors (ICIs) have emerged as a treatment for NSCLC, but their efficacy in KRAS-mutant NSCLC is debated.
Purpose of the Study:
- To evaluate the real-world effectiveness of ICIs in patients with advanced KRAS-mutant NSCLC.
- To determine if KRAS mutation status influences response to immunotherapy in NSCLC.
Main Methods:
- Retrospective analysis of 38 stage IV NSCLC patients treated with immunotherapy from January 2016 to December 2017.
- Collected data on KRAS and other mutations, ICI type, disease control rate (DCR), partial response (PR), progression-free survival (PFS), and overall survival (OS).
Main Results:
- KRAS-mutant NSCLC patients had a higher DCR (81% vs. 59%) and PR (62% vs. 49%) compared to KRAS wild-type.
- Progression-free survival (13.6 vs. 8.4 months) and overall survival (18.5 vs. 16.8 months) were also improved in KRAS-mutant patients.
- TP53 co-mutation appeared to negate the negative impact of STK11 and KRAS co-mutations on ICI response.
Conclusions:
- KRAS mutation status is a predictive marker for a superior response to immunotherapy in advanced NSCLC.
- The findings challenge previous assumptions about poor ICI response in certain KRAS-mutated NSCLC subtypes, particularly when TP53 is also mutated.
