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Successes and failures: what did we learn from recent first-line treatment immunotherapy trials in non-small cell
Jordi Remon1,2, Benjamin Besse1,3, Jean-Charles Soria4
1Cancer Medicine Department, Gustave Roussy, Villejuif, France.
Abstract:
The immune checkpoint inhibitors have significantly modified the therapeutic landscape of advanced non-small cell lung cancer in second-line and, more recently, first-line settings. Because of the superior outcome with pembrolizumab as an upfront strategy, PD-L1 status should now be considered a new reflex biomarker for guiding first-line treatment in patients with advanced non-small cell lung cancer. Improved responses have also been reported with the combination of immune checkpoint inhibitors and chemotherapy as the first-line treatment; however, this strategy has not yet been validated by phase III trial data and its interplay with PD-L1 status still requires clarification.In this manuscript we review the contradictory results of recent phase III trials with immune checkpoint inhibitors in the first-line setting, the potential reasons for discrepancies, and some of the remaining open questions related to the positioning of immune checkpoint inhibitors in the first-line setting of non-small cell lung cancer.
Insights
Immune checkpoint inhibitors, like pembrolizumab, are now standard for advanced non-small cell lung cancer. PD-L1 status is crucial for guiding first-line treatment decisions in these patients.
Area of Science:
- Oncology
- Immunotherapy
Background:
- Immune checkpoint inhibitors (ICIs) have transformed advanced non-small cell lung cancer (NSCLC) treatment.
- Pembrolizumab shows superior outcomes in first-line settings, establishing PD-L1 status as a key biomarker.
Purpose of the Study:
- To review contradictory Phase III trial results for ICIs in first-line NSCLC.
- To explore reasons for discrepancies and clarify the role of ICIs in first-line NSCLC treatment.
Main Methods:
- Review of recent Phase III clinical trial data.
- Analysis of immune checkpoint inhibitor efficacy and PD-L1 status interplay.
Main Results:
- Pembrolizumab demonstrates superior outcomes as an upfront strategy in advanced NSCLC.
- Combination of ICIs and chemotherapy shows promise but requires further validation and clarification of PD-L1 status role.
Conclusions:
- PD-L1 status is a critical biomarker for guiding first-line ICI therapy in advanced NSCLC.
- Further research is needed to clarify the optimal use of ICI and chemotherapy combinations and their relation to PD-L1 expression.
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