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Emerging biomarkers for neoadjuvant immune checkpoint inhibitors in operable non-small cell lung cancer
Monika Pradhan1, Mathieu Chocry2, Don L Gibbons1,3
1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Abstract:
The advent of immune checkpoint inhibitors (ICIs) has dramatically changed the treatment of patients with locally advanced unresectable and metastatic non-small cell lung cancer (NSCLC). Now, ICIs are undergoing evaluation as neoadjuvant therapy in patients with early-stage, resectable NSCLC using candidate surrogate endpoints of clinical efficacy, i.e., major pathologic response (MPR, ≤10% viable tumor cells in resected tumors). The initial results from early, small-scale trials are encouraging; however, they also reveal that a substantial number of patients with operable disease may not benefit from neoadjuvant ICIs. Consequently, much investigative effort is currently directed toward identifying mechanisms of resistance to ICI therapy in resectable NSCLC. There is also an urgent need for biomarkers that could be used to guide the clinical decision-making process and maximize the clinical benefit of ICIs in patients with early-stage, resectable NSCLC. Here, we summarize the initial results from the trials of neoadjuvant ICIs in patients with early-stage and locally advanced operable NSCLC and review the findings of studies investigating emerging biomarkers associated with those trials.
Insights
Immune checkpoint inhibitors (ICIs) show promise as neoadjuvant therapy for early-stage non-small cell lung cancer (NSCLC). Research is ongoing to identify resistance mechanisms and biomarkers for optimal ICI treatment in resectable NSCLC.
Area of Science:
- Oncology
- Immunotherapy
- Thoracic Surgery
Background:
- Immune checkpoint inhibitors (ICIs) have transformed treatment for advanced non-small cell lung cancer (NSCLC).
- ICIs are being investigated as neoadjuvant therapy for early-stage, resectable NSCLC.
- Early trials show encouraging results, but not all patients benefit from neoadjuvant ICIs.
Purpose of the Study:
- To summarize initial findings from neoadjuvant ICI trials in operable NSCLC.
- To review emerging biomarkers associated with neoadjuvant ICI therapy.
- To address the need for biomarkers guiding ICI treatment decisions in resectable NSCLC.
Main Methods:
- Review of early-stage clinical trials evaluating neoadjuvant ICIs in resectable NSCLC.
- Analysis of surrogate endpoints like major pathologic response (MPR).
- Examination of studies investigating biomarkers for ICI resistance and efficacy.
Main Results:
- Initial neoadjuvant ICI trials in NSCLC demonstrate encouraging outcomes.
- A significant portion of patients with operable NSCLC may not respond to neoadjuvant ICIs.
- Identifying mechanisms of resistance and predictive biomarkers is crucial.
Conclusions:
- Neoadjuvant ICIs represent a promising approach for early-stage NSCLC, but patient selection is key.
- Further research into ICI resistance mechanisms and biomarkers is urgently needed.
- Biomarkers are essential for guiding clinical decisions and maximizing treatment benefit.
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