Clinical definition of secondary resistance to immunotherapy in non-small cell lung cancer

Area of Science:

• Oncology
• Immunology
• Translational Medicine

Background:

• Immune checkpoint inhibitors (ICIs) like PD-1/PD-L1 and CTLA-4 blockade have transformed non-small cell lung cancer (NSCLC) treatment.
• Secondary resistance to immunotherapy (IO) is a significant clinical challenge, affecting initial responders.
• Lack of standardized definitions hinders clinical trial progress for patients with secondary resistance.

Purpose of the Study:

• To propose a practical clinical definition for secondary resistance to immunotherapy in NSCLC.
• To provide guidance for clinical trial design and facilitate future research in this area.
• To address the need for consistent criteria in evaluating patients with secondary resistance.

Main Methods:

• Expert panel convened to synthesize data from current investigational studies.
• Comprehensive review of treatment approaches including IO alone and chemotherapy plus IO.
• Development of a consensus-based definition for secondary resistance.

Main Results:

• A practical clinical definition for secondary resistance to immunotherapy in NSCLC was proposed.
• The definition encompasses both metastatic and neoadjuvant settings.
• Criteria were established for patients receiving IO alone and those treated with chemotherapy plus IO.

Conclusions:

• The proposed definition aims to standardize the identification of secondary resistance to IO in NSCLC.
• This consensus will aid in designing more consistent and interpretable clinical trials.
• Further updates to the consensus are anticipated as new data emerges.