Defining tumor resistance to PD-1 pathway blockade: recommendations from the first meeting of the SITC Immunotherapy...

Area of Science:

• Oncology
• Immunology
• Clinical Trials

Background:

• Cancer immunotherapy, particularly with programmed death receptor 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, is rapidly evolving.
• Evaluating new agents in patients previously treated with PD-(L)1 inhibitors presents challenges due to inconsistent definitions of resistance.
• Lack of standardized definitions complicates clinical trial design and interpretation of treatment response.

Purpose of the Study:

• To establish consensus clinical definitions for resistance to PD-(L)1 inhibitors.
• To address the unmet need for standardized criteria in cancer immunotherapy research.
• To provide guidance for designing clinical trials and analyzing resistance mechanisms.

Main Methods:

• Convening a multistakeholder taskforce by the Society for Immunotherapy of Cancer.
• Involving experts from academia, industry, and government.
• Generating consensus definitions for primary resistance, secondary resistance, and progression after treatment discontinuation.

Main Results:

• Consensus reached on clinical definitions for three scenarios of PD-(L)1 inhibitor resistance.
• Agreement on key issues including timeframes for resistance, need for confirmatory scans, and specific caveats.
• Established clear criteria to differentiate primary, secondary, and post-treatment discontinuation resistance.

Conclusions:

• The consensus definitions provide essential guidance for clinical trial design in cancer immunotherapy.
• Standardized definitions will improve the interpretation of results from studies involving PD-(L)1 inhibitors.
• This framework supports further research into the molecular and cellular mechanisms of resistance to immunotherapy.