Prognostic impact of immune-related adverse events in non-completers of durvalumab consolidation therapy for non-small cell lung cancer: a single-center retrospective cohort study

Introduction

Locally advanced non-small cell lung cancer (NSCLC) represents roughly one-third of all NSCLC diagnoses, with most cases being identified as surgically unresectable (1). Definitive concurrent or sequential platinum-based chemoradiotherapy (CRT) has long served as the standard therapeutic approach for patients maintaining a good performance status (2). However, long-term prognosis under this traditional strategy has been profoundly discouraging, typically yielding a median progression-free survival (PFS) of around 8 months and 5-year overall survival (OS) rates limited to 15–32% (1,3,4).

Recently, this established treatment landscape has undergone a dramatic paradigm shift with the clinical introduction of immune checkpoint inhibitors (ICIs) targeting the programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis. The pivotal phase III PACIFIC trial established consolidation therapy with durvalumab as the new standard of care for patients without disease progression following definitive CRT. The initial analysis demonstrated significantly prolonged PFS [13.8 vs. 5.6 months; hazard ratio (HR), 0.52; P<0.0001], while subsequent analyses showed improved OS and durable survival benefits extending beyond 5 years (5-7). Based on these results, durvalumab has been approved in many countries, including the United States, Europe, and Japan (8-10), and the PACIFIC regimen has become the standard consolidation strategy for unresectable locally advanced NSCLC. Optimizing durvalumab-based treatment strategies currently represents the state of the art in this setting (11).

Despite these substantial survival benefits, several clinically important questions remain unresolved in routine practice. Although one year of consolidation durvalumab is recommended, only 49% of patients in the PACIFIC trial completed the planned treatment duration, with premature discontinuation occurring mainly because of disease progression or adverse events (5). Consequently, the clinical significance of treatment completion and the outcomes of patients who discontinue therapy early remain incompletely understood.

Immune-related adverse events (irAEs) have attracted considerable attention as potential biomarkers of favorable antitumor activity during ICI treatment. Several studies have reported improved survival among patients who develop irAEs (12-14). However, this association remains controversial because patients with longer survival have a greater opportunity to develop irAEs (guarantee-time or immortal time bias) (15), while disease progression leading to early treatment discontinuation, corticosteroid administration for severe irAEs, and other time-dependent clinical factors may confound the observed relationship between irAEs and survival. Consequently, whether irAEs independently predict favorable outcomes in patients receiving consolidation durvalumab after CRT remains uncertain.

To address these unresolved issues, we conducted an exploratory, single-center retrospective study of patients with locally advanced NSCLC treated with consolidation durvalumab following definitive CRT. The primary objective was to evaluate clinical outcomes according to completion of the planned 1-year durvalumab treatment. We also characterized the reasons for early treatment discontinuation and explored the association between irAE development, treatment completion status, and long-term clinical outcomes. Given the retrospective design and the potential influence of multiple time-dependent confounding factors, these analyses were considered hypothesis-generating rather than intended to establish a causal relationship between irAEs and treatment efficacy. We present this article in accordance with the STROBE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-0603/rc).

Methods

Study design and patients

This retrospective study included 59 consecutive patients who received durvalumab consolidation therapy following definitive CRT for locally advanced or recurrent NSCLC at Fukuoka University Hospital between September 2018 and August 2024. In Japanese clinical practice, the indication for durvalumab consolidation following definitive CRT encompasses not only unresectable Stage III disease but also Stage II cases requiring pneumonectomy (where definitive CRT is preferred for organ preservation) and post-operative local recurrence without distant metastasis. Clinical characteristics, including age, sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS), smoking history, histological classification, disease stage, PD-L1 (22C3) expression levels, and the presence of actionable driver gene alterations, were retrospectively extracted from electronic medical records. Importantly, no patients had underlying pre-existing interstitial lung disease (ILD) at baseline using high-resolution computed tomography (HRCT). While this reflects standard domestic practice in Japan, we recognized that it may introduce potential clinical heterogeneity, which was carefully considered in our study design and limitations.

Tumor staging was determined for each case based on the 8th edition of the tumor, node, and metastasis (TNM) classification of malignant tumors (16). Routine CT evaluations were performed every 3 to 4 months during durvalumab treatment and every 3 to 6 months after treatment completion or discontinuation. Tumor response and disease progression were evaluated by the attending physicians according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (17). The severity of irAEs was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (18). To differentiate radiation pneumonitis from immune-related ILD, ILD was diagnosed as an irAE when pulmonary infiltrates extended outside the radiation field or when distinct exacerbation or new consolidation occurred during durvalumab therapy based on HRCT. In cases where differentiation between immune-related ILD and infectious pneumonia was challenging, lack of response to empirical antibiotic therapy, combined with multidisciplinary review, was used to exclude infection and attribute the causality to irAEs. OS was defined as the time from the initiation of durvalumab consolidation therapy to the date of death from any cause. PFS was calculated from durvalumab initiation until objective disease progression or all-cause mortality. Patients who were lost to follow-up or remained event-free at the data cutoff date (February 28, 2026) were censored at the date they were last known to be alive for OS, or the date of their last progression-free imaging evaluation for PFS.

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Medical Ethics Review Board of Fukuoka University (No. U22-02-006). As this was a retrospective study, the requirement for written informed consent was waived, and an opt-out option was provided via the institution’s official website (https://fukuoka.bvits.com/rinri/publish.aspx; accessed February 28, 2026).

Statistical analysis

Comparisons of patient characteristics were performed using the Mann-Whitney U test for age and Fisher’s exact test for categorical variables. For driver gene mutations and PD-L1 tumor proportion score (TPS) analysis, some cases had missing data. These missing values were categorized as "Unknown" and included in the descriptive and baseline analyses. All other variables had complete data. PFS and OS were estimated using the Kaplan-Meier method, and survival differences between groups were compared using the log-rank test.

To eliminate immortal time bias inherent to treatment duration comparisons between the completion and non-completion cohorts, a 12-month landmark analysis was performed. The landmark time point was set at 12 months after durvalumab initiation. Only patients who remained alive (for OS analysis) or alive and progression-free (for PFS analysis) at the 12-month landmark point were included. Survival times for the landmark analysis were calculated from the 12-month landmark time point.

To evaluate the prognostic impact of irAEs while strictly controlling for time-varying confounding and immortal time bias, time-dependent Cox proportional hazards regression models were constructed. The time-dependent covariate was defined based on the onset day of irAEs. To avoid model overfitting given the limited number of events, primary analyses relied on univariable time-dependent Cox models based on the events per variable rule. The proportional hazards assumption for the time-dependent model was evaluated using Schoenfeld residuals and was satisfied (χ²=1.41, P=0.23).

Furthermore, to evaluate the robustness of the findings in the non-completion cohort against potential confounding by baseline treatment discontinuation factors, a sensitivity analysis was performed using a stratified time-dependent Cox regression model stratified by the primary reason for discontinuation (disease progression vs. adverse events).

Results are expressed as HRs with 95% confidence intervals (CIs). All P values were two-sided, with statistical significance defined as P<0.05. All statistical analyses were conducted using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria) (19).

Results

Patient characteristics

As shown in the patient selection flowchart (Figure 1), a total of 59 consecutive patients were included in this study. The baseline patient characteristics according to the completion status of durvalumab therapy are summarized in Table 1. The median age of the entire cohort was 70 years (range, 48–81 years). The cohort was predominantly male (n=45) and had a high prevalence of smoking history (n=53). The majority of patients had an ECOG PS of 0 or 1 (n=55) and clinical stage III disease (n=51). Regarding histological classification, squamous cell carcinoma (n=29) was the most common, followed by adenocarcinoma (n=21). PD-L1 TPSs were ≥50% in 21 patients, 1–49% in 13, <1% in 8, and unknown in 17. Regarding baseline molecular profiles, driver gene mutation status was positive in 5 patients, negative in 34, and unknown in 20. Missing data for these biomarkers were primarily attributable to insufficient biopsy tissue samples. As predefined, these cases were categorized as “Unknown” and included in the baseline analyses. The objective response rate to prior CRT was 81%, with 48 patients achieving a partial response. There were no statistically significant differences in baseline clinical characteristics between the completion group (n=25) and the non-completion group (n=34). Although a numerical shift toward a higher proportion of PD-L1 TPS ≥50% was observed in the non-completion group (44% vs. 24%), the overall distribution of PD-L1 expression levels did not differ significantly between the two groups (P=0.09).

Figure 1 Patient selection and study flow diagram. CRT, chemoradiotherapy; NSCLC, non-small cell lung cancer.

Treatment delivery and reasons for discontinuation

Of the 59 patients, 25 (42%) successfully completed the 1-year durvalumab consolidation therapy. The remaining 34 patients (58%) discontinued treatment prematurely (Figure 1). The primary reasons for early discontinuation were disease progression (n=16) and adverse events (n=15), followed by patient preference (n=3). Among the 15 patients who discontinued due to adverse events, the most frequent causes were grade 2 or 3 ILD (n=9) and liver dysfunction (n=3) (Table 2).

Survival outcomes and the impact of durvalumab completion

During a median follow-up period of 53.6 months, 28 deaths [completers: 8/25 (32%); non-completers: 20/34 (59%)] and 36 progression events [completers: 9/25 (36%); non-completers: 27/34 (79%)] occurred. For the overall cohort, the median PFS was 18.7 months (95% CI: 12.2–44.6), and the median OS was 53.6 months [95% CI: 37.8–not reached (NR)]. Patients completing the 1-year durvalumab regimen demonstrated superior survival outcomes compared to non-completers. The median PFS was NR (95% CI: 27.2–NR) in the completion group versus 7.9 months (95% CI: 4.2–12.2) in the non-completion group (P<0.001), with 5-year PFS rates of 52% and 11%, respectively. Similarly, the median OS was significantly prolonged in the completion group (70.9 months; 95% CI: 44.6–NR) compared to the non-completion group (39.2 months; 95% CI, 20.0–53.6; P<0.01; Figure 2), yielding 5-year OS rates of 61% and 22%, respectively.

Figure 2 Progression-free survival and overall survival in patients with locally advanced non-small cell lung cancer who received durvalumab consolidation therapy following chemoradiotherapy, analyzed according to the completion of 1-year durvalumab therapy. CI, confidence interval; NR, not reached; OS, overall survival; PFS, progression-free survival.

To adjust for potential immortal-time bias, a 12-month landmark analysis was conducted. For OS analysis, 49 patients who survived beyond 12 months (completers, n=25; non-completers, n=24) were evaluated. The median OS calculated from the 12-month landmark point was significantly longer in the completion group compared to the non-completion group [58.9 months (95% CI: 32.6–NR) vs. 33.9 months (95% CI: 8.3–42.1); P=0.04; Figure 3]. For PFS analysis, among patients who remained progression-free at 12 months (completers, n=25; non-completers, n=10), the completion group demonstrated a numerical trend toward superior PFS post-landmark compared to the non-completion group [median PFS: NR (95% CI: 15.2–NR) vs. 12.9 months (95% CI: 2.8–NR); P=0.07; Figure 3].

Figure 3 PFS and OS in patients with locally advanced non-small cell lung cancer who received durvalumab consolidation therapy following chemoradiotherapy, evaluated using a 12-month landmark analysis according to treatment completion status. CI, confidence interval; NR, not reached; OS, overall survival; PFS, progression-free survival.

Impact of irAEs on survival

Overall, irAEs occurred in 25 patients (42%), comprising 10 of 25 in the completion group and 15 of 34 in the non-completion group. The detailed profile of irAEs, including organ involvement and severity, is summarized in Table S1. In the overall cohort, the occurrence of irAEs did not significantly impact median PFS (19.6 vs. 18.7 months, P=0.28) or median OS (53.6 vs. 45.9 months, P=0.15; Figure S1). In the time-dependent Cox proportional hazards regression analysis for the overall cohort, the onset of irAEs was associated with a trend toward a reduced mortality risk for OS (HR =0.591; 95% CI: 0.271–1.290; P=0.19). For PFS, time-dependent Cox analysis revealed no significant association between irAE onset and disease progression or death (HR =0.893; 95% CI: 0.449–1.775; P=0.75; Table 3). However, a distinct survival benefit associated with irAEs was identified in the subgroup of patients who failed to complete durvalumab therapy (n=34). Within this non-completion group, patients who experienced irAEs achieved a substantially longer median PFS (14.8 vs. 4.4 months, P=0.01) and median OS [53.6 (95% CI: 13.4–NR) vs. 20.3 months (95% CI: 10.2–45.9), P=0.03; Figure 4] compared to those without irAEs. In the time-dependent Cox proportional hazards regression analysis restricted to non-completers, irAE onset demonstrated a trend toward improved PFS (HR =0.586; 95% CI: 0.255–1.348; P=0.21) and a statistically significant reduction in mortality risk for OS (HR =0.384; 95% CI: 0.147–0.999; P=0.0498; Table 3). Notably, within this non-completion cohort, patients with irAEs achieved a 5-year OS rate of 43%, whereas the 5-year OS rate was 0% in those without irAEs. To confirm the robustness of these findings against potential confounding by treatment discontinuation reasons, a sensitivity analysis stratifying by the primary reason for discontinuation [disease progression (n=16) vs. adverse events (n=15)] was performed. The stratified time-dependent Cox model consistently demonstrated a trend toward reduced mortality risk associated with irAE onset (HR =0.44; 95% CI: 0.11–1.72; P=0.24).

Figure 4 PFS and OS in patients with locally advanced non-small cell lung cancer who received durvalumab consolidation therapy following chemoradiotherapy, analyzed according to immune-related adverse events status in the non-completion group. CI, confidence interval; irAE, immune-related adverse event; NR, not reached; OS, overall survival; PFS, progression-free survival.

Subsequent therapy after disease progression

In the completion group, 7 patients experienced disease progression. Of these, 6 patients (86%) received active subsequent systemic therapies, including platinum-based combinations (n=4), docetaxel plus ramucirumab (n=1), pemetrexed (n=1), and only 1 patient transitioned to best supportive care (BSC).

In the non-completion group, 25 patients experienced disease progression. Within this group, a distinct difference in treatment intensity was observed based on the occurrence of irAEs. Among the irAE-negative subgroup (n=16 with disease progression), 13 patients (81%) received intensive systemic therapies: combination immunotherapy (n=5), platinum-based combinations (n=4), docetaxel plus ramucirumab (n=3), and targeted therapy (n=1). Additionally, one patient received radiotherapy alone, and two transitioned to BSC. Conversely, in the irAE-positive subgroup (n=9 with disease progression), only 4 patients (44%) received active systemic therapy: targeted therapy (n=2), platinum-based combination (n=1), and pemetrexed (n=1). A notably higher proportion of patients transitioned to BSC (n=4) or received radiotherapy alone (n=1) (Table 4).

Discussion

In this retrospective study, patients who completed the full 1-year durvalumab regimen achieved favorable long-term outcomes. Importantly, even after eliminating immortal time bias through a 12-month landmark analysis, treatment completers consistently demonstrated robust long-term survival, with a 5-year OS rate of 61% and a 5-year PFS rate of 52%. These results are generally consistent with the landmark PACIFIC trial’s post-hoc analysis, which reported a 5-year OS of 66% and a 5-year PFS of 43% for treatment completers (20). Although the observed 5-year PFS numerically exceeded that of the trial, these findings should be interpreted with caution given the small sample size and retrospective nature of our cohort.

This effectiveness is also supported by the AYAME study (21)—the largest Japanese prospective observational study (n=511)—which reported a median real-world PFS of 23.2 months, confirming the clinical utility of durvalumab in the Japanese real-world setting. However, achieving this 1-year milestone remains a significant challenge in clinical practice. In our cohort, the completion rate was 42%, which is remarkably consistent with the 41% completion rate reported in the AYAME study. Consequently, 58% (n=34) of our patients required discontinuation, highlighting a reproducible gap between clinical trial outcomes and real-world persistence.

An important observation of this study is the potential association between irAEs and survival. The SUBMARINE study, a nationwide multicenter prospective study, demonstrated that patients who developed mild irAEs tended to have favorable survival outcomes (22). Conversely, the study reported that non-mild irAEs requiring intensive interventions, such as severe ILD, significantly worsened PFS. This suggests that while certain toxicities may serve as indicators of treatment efficacy, severe inflammation and the subsequent need for potent immunosuppression may potentially counteract the anti-tumor immune response.

This clinical complexity is particularly relevant in the Japanese population, where the risk of ILD is inherently high. In the AYAME study, ILD occurred in 387 patients (76%), with a severity breakdown of 35% Grade 1, 28% Grade 2, 11% Grade 3, and 2% Grade 5 (21). Furthermore, 16.0% of patients experienced multiple overlapping events, creating significant barriers to treatment continuation. A recent meta-analysis reinforces this challenge; analyzing 17 real-world studies (n=3,125), the authors found that the 1-year treatment completion rate was only 36%, suggesting that severe pneumonitis frequently limits treatment duration (23).

In addition, the SUBMARINE study noted that the occurrence of irAEs is independent of immunological characteristics or clinical background, making them difficult to predict. Nevertheless, post-hoc analyses of the PACIFIC trial demonstrated that the development of irAEs was associated with a survival benefit (24). Specifically, regarding ILD, even patients who developed Grade ≥2 pneumonitis and were forced to discontinue treatment still derived a significant clinical benefit from durvalumab (OS HR, 0.63) (25). These findings, alongside our data, suggest that if ILD is managed effectively and severe exacerbation is avoided, the onset of manageable ILD might reflect an active immune response.

Our analysis identified an intriguing trend within the non-completion group: a 5-year OS of 43% in those with irAEs versus 0% in those without. To rigorously evaluate this observation and mitigate potential immortal time bias inherent to post-baseline events, we employed time-dependent Cox proportional hazards regression, which confirmed a statistically significant reduction in mortality risk among non-completers with irAEs. Furthermore, our sensitivity analysis demonstrated that this favorable trend persisted independently of the primary reason for discontinuation. While previous evidence (23) emphasizes that longer maintenance periods optimize survival, our findings raise the hypothesis of a potential counter-phenomenon in patients who discontinue early. Despite receiving subsequent systemic treatments, the irAE-negative non-completers failed to achieve long-term survival. In contrast, the irAE-positive group exhibited a favorable OS trend despite a higher transition to BSC. This observation aligns with previous reports indicating that early immune-related events may reflect an active immune response (26). However, whether irAE onset serves as a direct driver of long-term survival or merely a surrogate marker requires further objective evaluation, particularly given the small event numbers. Nevertheless, these findings imply that early discontinuation of durvalumab due to a manageable irAE does not necessarily preclude durable disease control. Conversely, the 0% OS rate observed in irAE-negative non-completers represents a challenging clinical subgroup that warrants further investigation. In our cohort, these patients received second-line treatments, such as platinum combinations or docetaxel plus ramucirumab, according to standard guidelines. Despite these interventions, the absence of long-term survivors suggests that this subgroup may exhibit primary resistance to both ICIs and subsequent cytotoxic chemotherapy.

Therefore, our findings suggest that the onset of manageable irAEs may serve as a potential prognostic signal in clinical practice. This highlights the importance of baseline risk assessment and careful toxicity management. Pre-treatment evaluation of interstitial lung abnormalities, performance status, and PD-L1 expression may assist clinicians in identifying patient risk profiles prior to therapy (27). For patients who discontinue treatment early without developing irAEs, close clinical monitoring is essential, as standard subsequent therapy alone may be insufficient to achieve long-term remission in this population. Furthermore, a multidisciplinary approach remains important to maximize treatment tolerance and patient safety through proactive toxicity management.

This study has several limitations. First, its retrospective, single-center design with a small sample size (n=59) limits generalizability and introduces potential selection bias. Second, although time-dependent Cox regression and landmark analyses were applied to minimize immortal time bias, unmeasured confounding may persist. Third, the small non-completion cohort (n=34) reduced statistical power. Fourth, including post-operative local recurrence alongside unresectable Stage III disease may introduce clinical heterogeneity. Fifth, retrospective reliance on medical records carries a risk of outcome misclassification, such as subtle distinctions between irAEs, radiation pneumonitis, and infection, or underreporting of low-grade adverse events. Consequently, these findings should be regarded as hypothesis-generating, and larger prospective cohort studies are required for validation. Finally, future studies incorporating longitudinal circulating tumor DNA (ctDNA) or cytokine dynamics are needed to objectively evaluate the kinetics of durable immune activation and guide personalized treatment strategies.

Conclusions

While 1-year durvalumab completion remains the primary clinical objective, manageable irAEs—particularly ILD in Japanese patients—may be associated with long-term survival despite premature discontinuation. Although this favorable trend suggests a potential prognostic signal associated with immune-related events, given the small retrospective cohort, they remain hypothesis-generating. Clinical strategies should optimize therapeutic benefit while ensuring patient safety through risk assessment, toxicity management, and close follow-up.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-0603/rc

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-0603/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-0603/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-0603/coif). Masaki Fujita, H.I., and T.Y. have received honoraria for lectures from AstraZeneca K.K. outside the submitted work. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Medical Ethics Review Board of Fukuoka University (No. U22-02-006). As this was a retrospective study, the requirement for written informed consent was waived, and an opt-out option was provided via the institution’s official website (https://fukuoka.bvits.com/rinri/publish.aspx; accessed February 28, 2026).

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Aupérin A, Le Péchoux C, Rolland E, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol 2010;28:2181-90. [Crossref] [PubMed]
2. Yoon SM, Shaikh T, Hallman M. Therapeutic management options for stage III non-small cell lung cancer. World J Clin Oncol 2017;8:1-20. [Crossref] [PubMed]
3. Ahn JS, Ahn YC, Kim JH, et al. Multinational Randomized Phase III Trial With or Without Consolidation Chemotherapy Using Docetaxel and Cisplatin After Concurrent Chemoradiation in Inoperable Stage III Non-Small-Cell Lung Cancer: KCSG-LU05-04. J Clin Oncol 2015;33:2660-6. [Crossref] [PubMed]
4. Bradley JD, Hu C, Komaki RR, et al. Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non-Small-Cell Lung Cancer. J Clin Oncol 2020;38:706-14. [Crossref] [PubMed]
5. Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med 2017;377:1919-29. [Crossref] [PubMed]
6. Antonia SJ, Villegas A, Daniel D, et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med 2018;379:2342-50. [Crossref] [PubMed]
7. Spigel DR, Faivre-Finn C, Gray JE, et al. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Clin Oncol 2022;40:1301-11. [Crossref] [PubMed]
8. US Food and Drug Administration. IMFINZI (durvalumab) label. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761069s018lbl.pdf. Accessed February 28, 2026.
9. European Medicines Agency. Summary of product characteristics, IMFINZI (durvalumab). Available online: https://www.ema.europa.eu/en/documents/product-information/imfinzi-epar-product-information_en.pdf. Accessed February 28, 2026.
10. PMDA. List of approved products: financial year 2018. Available online: https://www.pmda.go.jp/english/review-services/reviews/approved-information/drugs/0002.html. Accessed February 28, 2026.
11. Desai P, Edelman MJ, Kumar S. State-of-the-Art Advances and Management of Unresectable Locally Advanced (stage III) Non-Small Cell Lung Cancer. Am Soc Clin Oncol Educ Book 2026;46:e518252. [Crossref] [PubMed]
12. Curkovic NB, Bai K, Ye F, et al. Incidence of Cutaneous Immune-Related Adverse Events and Outcomes in Immune Checkpoint Inhibitor-Containing Regimens: A Systematic Review and Meta-Analysis. Cancers (Basel) 2024;16:340. [Crossref] [PubMed]
13. Hashimoto T, Karashima T, Kamada K, et al. Relationship between immune-related adverse events and treatment outcome of immune checkpoint inhibitors for advanced non-small cell lung cancer: a retrospective cohort study. J Thorac Dis 2026;18:89. [Crossref] [PubMed]
14. Ezdoglian A, Tsang-A-Sjoe M, Khodadust F, et al. Monocyte-related markers as predictors of immune checkpoint inhibitor efficacy and immune-related adverse events: a systematic review and meta-analysis. Cancer Metastasis Rev 2025;44:35. [Crossref] [PubMed]
15. Zhao L, Li F, Zhu Z, et al. Meta-analysis of cutaneous immune-related adverse events in NSCLC: Accounting for treatment heterogeneity and immortal time bias. Lung Cancer 2026;216:109422. [Crossref] [PubMed]
16. World Health Organization. Cancer. Available online: https://www.who.int/health-topics/cancer#tab=tab_1. Accessed February 28, 2026.
17. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47. [Crossref] [PubMed]
18. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Available online: https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50. Accessed February 28, 2026.
19. Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant 2013;48:452-8. [Crossref] [PubMed]
20. AstraZeneca. IMFINZI HCP. PACIFIC Trial Efficacy: 5-year Overall Survival (OS) and Progression-Free Survival (PFS) Updates. Available online: https://www.imfinzihcp.com/nsclc/stage-3/efficacy.html. Accessed February 28, 2026.
21. Kenmotsu H, Saito Y, Ninomiya K, et al. Long-Term Safety and Effectiveness of Durvalumab in Unresectable Stage III NSCLC in Japan: A Multicenter Prospective Study (AYAME). J Thorac Oncol 2026;21:160-73. [Crossref] [PubMed]
22. Haratani K, Nakamura A, Mamesaya N, et al. Tumor Microenvironment Landscape of NSCLC Reveals Resistance Mechanisms for Programmed Death-Ligand 1 Blockade After Chemoradiotherapy: A Multicenter Prospective Biomarker Study (WJOG11518L:SUBMARINE). J Thorac Oncol 2023;18:1334-50. [Crossref] [PubMed]
23. Li Y, Deng G, Liang N, et al. Chemoradiotherapy Combined with Immunotherapy in Stage III Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Efficacy and Safety Outcomes. Oncology 2024;102:382-98. [Crossref] [PubMed]
24. Naidoo J, Vansteenkiste JF, Faivre-Finn C, et al. Characterizing immune-mediated adverse events with durvalumab in patients with unresectable stage III NSCLC: A post-hoc analysis of the PACIFIC trial. Lung Cancer 2022;166:84-93. [Crossref] [PubMed]
25. Vansteenkiste JF, Naidoo J, Faivre-Finn C, et al. Symptomatic Pneumonitis With Durvalumab After Concurrent Chemoradiotherapy in Unresectable Stage III NSCLC. JTO Clin Res Rep 2024;5:100638. [Crossref] [PubMed]
26. Schadendorf D, Wolchok JD, Hodi FS, et al. Efficacy and Safety Outcomes in Patients With Advanced Melanoma Who Discontinued Treatment With Nivolumab and Ipilimumab Because of Adverse Events: A Pooled Analysis of Randomized Phase II and III Trials. J Clin Oncol 2017;35:3807-14. [Crossref] [PubMed]
27. Kashihara T, Nakayama Y, Okuma K, et al. Impact of interstitial lung abnormality on survival after adjuvant durvalumab with chemoradiotherapy for locally advanced non-small cell lung cancer. Radiother Oncol 2023;180:109454. [Crossref] [PubMed]