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Disease Kinetics and Practice Patterns in More Than or Equal to 4-Year Long-Term Beneficiaries of Immune Checkpoint
Masahiro Torasawa1, Yoshihiro Masui1, Keita Miura2
1Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Introduction:
Immune checkpoint inhibitors (ICIs) have enabled durable responses in a subset of patients with advanced NSCLC; however, the clinical trajectories and patterns of late disease progression among long-term survivors remain poorly characterized.
Methods:
This multicenter retrospective study enrolled patients with advanced NSCLC who received ICI-containing therapy between January 2015 and April 2020. Long-term beneficiaries (LTBs) were defined as patients who achieved both an overall survival (OS) of more than or equal to 4 years and a time to next cytotoxic chemotherapy of more than or equal to 4 years. We performed 4-year landmark analyses, characterized late progression (first radiographic progression ≥4 y from ICI initiation), and evaluated cause-specific mortality using competing risk analysis.
Results:
Of 3144 patients, 537 (17%) survived more than or equal to 4 years, and 295 (9.4%) were LTBs (median follow-up: 68.6 mo); only 8.1% were lost to follow-up at the data cutoff. ICI was initiated as first-line therapy in 63% of the patients. Among the 235 LTBs without progression at 4 years, 66% discontinued ICI. The lung cancer-specific OS rates were 97.8% and 88.0% at 6 and 8 years, respectively. Late progression occurred in 26 patients (11.1%); all had less than or equal to five lesions, and 84.6% demonstrated indolent progression with growth speeds less than or equal to 10 mm/mo. Local therapy was selected in 42% of the patients after progression. Of 22 deaths more than or equal to 4 years post-ICI, only seven (32%) were lung cancer related, whereas 15 (68%) were from other causes, including secondary malignancies. Competing risk analysis revealed that other-cause mortality consistently exceeded lung cancer-related mortality.
Conclusions:
LTBs without progression at 4 years achieved durable control, with lung cancer-specific OS approaching 90% at 8 years of follow-up. Late progression is uncommon, limited in extent, and often treated locally. The predominance of non-lung cancer-related mortality underscores the importance of comprehensive survivorship care.
Insights
Long-term survivors of advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) show durable control, with late progression being rare and manageable. Non-lung cancer causes dominate mortality, highlighting the need for comprehensive survivorship care.
Area of Science:
- Oncology
- Immunotherapy
- Lung Cancer Research
Background:
- Immune checkpoint inhibitors (ICIs) offer durable responses in advanced non-small cell lung cancer (NSCLC).
- Clinical outcomes and late progression patterns in long-term NSCLC survivors treated with ICIs are not well understood.
Purpose of the Study:
- To characterize the clinical trajectories of long-term beneficiaries (LTBs) of ICI therapy in advanced NSCLC.
- To define and analyze patterns of late disease progression (≥4 years post-ICI initiation).
- To evaluate cause-specific mortality in long-term NSCLC survivors.
Main Methods:
- Retrospective multicenter study of advanced NSCLC patients receiving ICI therapy (Jan 2015-Apr 2020).
- Defined LTBs as patients with ≥4 years overall survival and ≥4 years time to next cytotoxic chemotherapy (TTNC).
- Conducted 4-year landmark analyses, characterized late progression, and used competing risk analysis for mortality.
Main Results:
- 9.4% of 3,144 patients (295) met LTB criteria (median follow-up 68.6 months).
- Lung cancer-specific overall survival (OS) reached 97.8% at 6 years and 88.0% at 8 years.
- Late progression occurred in 11.1% of LTBs, was limited in extent (≤5 lesions), and often indolent (≤10 mm/month growth); 42% received local therapy.
- Non-lung cancer mortality (e.g., secondary malignancies) predominated over lung cancer deaths in long-term survivors.
Conclusions:
- Long-term beneficiaries without progression at 4 years achieve durable disease control with high long-term OS.
- Late progression is infrequent, indolent, and amenable to local treatment.
- The high rate of non-lung cancer mortality emphasizes the critical need for comprehensive survivorship care in advanced NSCLC survivors.
