The frontier of neoadjuvant therapy in non-small cell lung cancer beyond PD-(L)1 agents
Marco Sposito1, Serena Eccher1, Ilaria Scaglione1
1Section of Innovation Biomedicine - Oncology Area, Department of Engineering for Innovation Medicine (DIMI), University of Verona and Verona University Hospital Trust, Verona, Italy.
Introduction:
While surgical resection is the cornerstone of treatment for resectable lung cancer, neoadjuvant/adjuvant chemotherapy has shown limited improvement in survival rates over the past decades. With the success of immune checkpoint inhibitors (ICIs) in advanced NSCLC, there is growing interest in their application in earlier stages of the disease. Recent approvals for neoadjuvant/adjuvant ICIs in stage II-IIIA NSCLC highlight this shift in treatment paradigms.
Areas Covered:
In this review, we aim to explore available data regarding alternative agents beyond the PD-(L)1 inhibitors, such as monoclonal antibodies against CTLA4, LAG3, TIGIT, antiangiogenic drugs, and novel therapies (antibody drug conjugates, bispecific antibodies) in neoadjuvant/perioperative regimens.
Expert Opinion:
Novel agents and combinations (with or without ICI or/and chemotherapy), guided by molecular profiling and immune phenotyping, showed promise in improving surgical and survival outcomes. Crucial is, also in early setting, to identifying biomarkers predictive of treatment efficacy in order to personalize neoadjuvant/perioperative treatment strategies.
Insights
Exploring novel therapies beyond PD-(L)1 inhibitors for early-stage lung cancer shows promise. Identifying predictive biomarkers is crucial for personalizing neoadjuvant/perioperative treatment strategies and improving outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Surgical Oncology
Background:
- Surgical resection is standard for resectable lung cancer, but chemotherapy offers limited survival benefits.
- Immune checkpoint inhibitors (ICIs) show success in advanced non-small cell lung cancer (NSCLC).
- There's increasing interest in using ICIs for earlier stages of NSCLC, with recent approvals for neoadjuvant/adjuvant settings.
Purpose of the Study:
- To review data on alternative agents beyond PD-(L)1 inhibitors for neoadjuvant/perioperative regimens.
- To explore novel therapies including CTLA4, LAG3, TIGIT antibodies, antiangiogenic drugs, and antibody-drug conjugates.
- To discuss the role of molecular profiling and immune phenotyping in guiding treatment.
Main Methods:
- Literature review of available data on novel agents and combinations.
- Analysis of studies investigating neoadjuvant/perioperative treatments for early-stage NSCLC.
- Exploration of biomarkers for predicting treatment efficacy.
Main Results:
- Novel agents and combinations demonstrate potential in enhancing surgical and survival outcomes.
- Personalized neoadjuvant/perioperative strategies are being developed.
- Biomarker identification is key for treatment efficacy.
Conclusions:
- Alternative agents and novel therapies show promise in early-stage lung cancer treatment.
- Personalized approaches guided by biomarkers are essential for optimizing neoadjuvant/perioperative strategies.
- Further research is needed to fully elucidate the role of these novel agents.
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