Evaluation of the Molecular Landscape in PD-L1 Positive Metastatic NSCLC: Data from Campania, Italy
Pasquale Pisapia1, Antonino Iaccarino1, Caterina De Luca1
1Department of Public Health, University of Naples Federico II, 80131 Naples, Italy.
Background:
Immune-checkpoint inhibitors (ICIs) have increased and improved the treatment options for patients with non-oncogene-addicted advanced stage non-small cell lung cancer (NSCLC). However, the role of ICIs in oncogene-addicted advanced stage NSCLC patients is still debated. In this study, in an attempt to fill in the informational gap on the effect of ICIs on other driver mutations, we set out to provide a molecular landscape of clinically relevant oncogenic drivers in programmed death-ligand 1 (PD-L1) positive NSCLC patients.
Methods:
We retrospectively reviewed data on 167 advanced stage NSCLC PD-L1 positive patients (≥1%) who were referred to our clinic for molecular evaluation of five driver oncogenes, namely, EGFR, KRAS, BRAF, ALK and ROS1.
Results:
Interestingly, n = 93 (55.7%) patients showed at least one genomic alteration within the tested genes. Furthermore, analyzing a subset of patients with PD-L1 tumor proportion score (TPS) ≥ 50% and concomitant gene alterations (n = 8), we found that n = 3 (37.5%) of these patients feature clinical benefit with ICIs administration, despite the presence of a concomitant KRAS gene alteration.
Conclusions:
In this study, we provide a molecular landscape of clinically relevant biomarkers in NSCLC PD-L1 positive patients, along with data evidencing the clinical benefit of ICIs in patient NSCLC PD-L1 positive alterations.
Insights
Immune-checkpoint inhibitors (ICIs) show clinical benefit in advanced non-small cell lung cancer (NSCLC) patients with PD-L1 positive alterations. This study details the molecular landscape and ICI efficacy in these patients, including those with KRAS alterations.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Immune-checkpoint inhibitors (ICIs) have transformed advanced non-small cell lung cancer (NSCLC) treatment for non-oncogene-addicted cases.
- The efficacy of ICIs in oncogene-addicted NSCLC remains under investigation.
- Understanding the molecular drivers in PD-L1 positive NSCLC is crucial for optimizing treatment strategies.
Purpose of the Study:
- To delineate the molecular landscape of oncogenic drivers in PD-L1 positive advanced NSCLC patients.
- To investigate the role and efficacy of ICIs in NSCLC patients with specific driver mutations.
- To bridge the knowledge gap regarding ICIs' impact on various driver mutations in NSCLC.
Main Methods:
- Retrospective analysis of 167 advanced NSCLC patients with PD-L1 positivity (≥1%).
- Molecular evaluation for five key driver oncogenes: EGFR, KRAS, BRAF, ALK, and ROS1.
- Assessment of clinical benefit from ICIs administration in relation to identified genomic alterations.
Main Results:
- Over half (55.7%) of the patients harbored at least one genomic alteration in the tested driver genes.
- In a subset of patients with high PD-L1 TPS (≥50%) and co-occurring alterations, 37.5% experienced clinical benefit from ICIs.
- Notably, some patients with KRAS alterations demonstrated clinical benefit from ICIs.
Conclusions:
- This study presents a molecular profile of PD-L1 positive NSCLC patients, highlighting common driver alterations.
- Evidence suggests that ICIs can provide clinical benefit in PD-L1 positive NSCLC patients, even with co-occurring driver mutations like KRAS.
- Further research into ICI efficacy across diverse molecular subtypes of NSCLC is warranted.
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