AUTHOR=Wang Jian , Gao Qijia , Chen Jianxin 

TITLE=Efficacy and safety of immune checkpoint inhibitor rechallenge therapy in the treatment of advanced acquired immune-resistant non-small cell lung cancer: a retrospective study

JOURNAL=Frontiers in Oncology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1621860

DOI=10.3389/fonc.2025.1621860

ISSN=2234-943X

ABSTRACT=BackgroundPatients with advanced non-small cell lung cancer who have failed first-line immunotherapy and lack driver gene mutations face limited options for subsequent treatment. A working group recently proposed updated clinical diagnostic criteria for acquired immune resistance. Based on these criteria, this study evaluated the efficacy and safety of immune rechallenge therapy in patients with advanced NSCLC exhibiting acquired resistance.MethodsThe study involved 13 patients diagnosed with advanced immune-acquired resistance NSCLC. These patients initially exhibited a partial response to immunotherapy but experienced disease progression within six months following their last immune checkpoint inhibitors (ICIs) treatment. Subsequently, they received ICIs again. The outcomes assessed included the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. PFS1 refers to the time from the first administration of anti–PD-1/PD-L1 blockade therapy to PD. PFSR was defined as the duration from the first day of the second ICIs administration to disease progression, death, or the last follow-up date. OS was defined as the time from the first day of the second ICIs administration to the date of death or the last follow-up date.ResultsThe median age was 67 years, and 76.9% of patients were male. The disease control rate (DCR) was 61.5%, with an ORR of 0%. The median PFSR was 2.90 months (95% CI, 1.97–3.83), and the median PFS1 was 5.97 months (95% CI, 4.13–7.81). Poor ECOG performance status was significantly associated with shorter PFS (HR = 6.839, 95% CI: 1.557–30.032, p = 0.011).During initial ICIs treatment, the most common adverse events were fatigue (46.1%) and anemia (38.5%). Grade 3–4 toxicities included anemia and neutropenia (15.4% each), leukopenia (7.8%), and fatigue (7.8%). In the ICIs rechallenge phase, anemia (38.5%) and fatigue (30.7%) remained the most frequent adverse events, with only one Grade 3–4 event reported (anemia, 7.8%).ConclusionsPatients with advanced non-small cell lung cancer who exhibit immune-acquired resistance may still derive clinical benefit from rechallenging with immune checkpoint inhibitors, particularly in those with a favorable ECOG performance status. Further prospective clinical trials and molecular investigations are necessary to validate these findings and better define the patient subgroups most likely to benefit from this therapeutic approach.