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Patterns of Failure in Patients With Advanced Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitors
Rong Chai1, Yipengchen Yin1, Xuwei Cai1
1Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Objective:
The advent of immune checkpoint inhibitors (ICIs) has rapidly transformed the treatment paradigm of non-small cell lung cancer (NSCLC). Despite the durability of response to ICIs, the vast majority of patients will later develop progression. However, the failure patterns of ICI treatment are unknown. Here, our study explored the failure patterns in advanced NSCLC patients treated with ICIs.
Methods:
A cohort of 156 IIIB or IV NSCLC patients treated with first-/second-line ICIs were retrospectively analyzed. Patients who experienced clinical benefit and then developed progression were identified. The disease progression patterns were divided into three categories: progression in new sites, progression in existing sites, and combined progression. The number of progression sites was also recorded.
Results:
Before the cutoff date, 91 (77.1%) patients had experienced disease progression; 34% of patients had progressed in the last 9 months of the first year. Fifty-three (58.2%) patients had developed progression at existing lesions, and 56 (61.5%) patients had shown ≤2 progression sites (oligo-progression). In patients with oligo-progression, the median time of disease progression was 8.23 months and the counterpart (systemic progression) was 5.97 months. The oligo-progression patients showed prolonged median overall survival (27.23 months) compared with patients with systemic progression (18.87 months).
Conclusions:
Failure patterns of ICI therapy were predominantly "existing" sites, and the most common lesions of progression were the lung and lymph nodes. Most patients experienced oligo-progression which occurred later than systemic progression and showed prolonged overall survival. The control of the local lesions might be beneficial to improve ICI treatment efficacy.
Insights
Immune checkpoint inhibitors (ICIs) for non-small cell lung cancer often lead to progression at existing sites, with most patients experiencing limited, late-onset oligo-progression. This pattern is associated with improved overall survival, suggesting localized treatment may enhance efficacy.
Area of Science:
- Oncology
- Immunotherapy
- Lung Cancer Research
Background:
- Immune checkpoint inhibitors (ICIs) have revolutionized non-small cell lung cancer (NSCLC) treatment.
- Despite initial responses, most patients eventually experience disease progression.
- Understanding ICI failure patterns is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the failure patterns of immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (NSCLC).
- To characterize the sites and extent of disease progression after ICI treatment.
- To correlate progression patterns with overall survival in NSCLC patients.
Main Methods:
- Retrospective analysis of 156 patients with IIIB or IV NSCLC treated with first-/second-line ICIs.
- Categorization of progression into new sites, existing sites, or combined progression.
- Recording the number of progression sites and comparing outcomes for oligo-progression versus systemic progression.
Main Results:
- 77.1% of patients experienced disease progression, with 34% progressing in the latter half of the first year.
- Progression at existing lesions occurred in 58.2% of patients.
- Oligo-progression (≤2 sites) was observed in 61.5% of patients, associated with a longer median progression time (8.23 vs. 5.97 months) and improved overall survival (27.23 vs. 18.87 months).
Conclusions:
- ICI failure in NSCLC predominantly involves progression at existing sites, particularly in the lungs and lymph nodes.
- Oligo-progression is a common failure pattern, occurring later than systemic progression and correlating with better overall survival.
- Targeting local lesion control may enhance the effectiveness of ICI therapy in NSCLC.
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