Background: Immune checkpoint inhibitors (ICIs) have shown significant improvements in patients with advanced non–small cell lung cancer (NSCLC). One of the major issues with ICIs is determining the optimal treatment duration.Methods: This multicenter, retrospective study analyzed clinical outcomes in patients with NSCLC who completed 2 years of ICI therapy or were treated for more than 6 months and then discontinued ICIs without disease progression at 11 medical centers in Korea between August 2017 and December 2020.Results: Ninety‐six patients who completed 2 years of ICIs were reviewed. The median durations of treatment and follow‐up were 24.0 and 33.9 months, respectively. The objective response rate (ORR) was 85.4%. The median progression‐free survival (PFS) and overall survival (OS) periods were not reached. After completion, the PFS and OS rates were 81.1% and 96.4%, respectively, at 12 months. Forty‐three patients were identified who discontinued ICIs without disease progression: 26 (60.5%) for adverse events and 17 (39.5%) for other causes. The median durations of treatment and follow‐up were 10.5 and 21.2 months, respectively. The ORR was 90.7%. The median PFS and OS periods were not reached. After discontinuation, the PFS and OS rates were 71.0% and 90.0%, respectively, at 12 months.Conclusions: A significantly high proportion of patients who completed 2 years of ICI therapy continued to experience long‐term PFS. Even if ICIs are discontinued after 6 months in patients without disease progression, they may achieve a durable response and facilitate long‐term survival.Lay Summary: The optimal treatment duration for immune checkpoint inhibitors (ICIs) remains to be determined. This study reports the long‐term outcomes of patients with non–small cell lung cancer who completed 2 years of ICI therapy or achieved a durable response after the discontinuation of ICIs without disease progression in real‐world practice. A significantly high proportion of patients who completed 2 years of ICIs continued to experience long‐term progression‐free survival. In addition, even if ICIs are discontinued after 6 months in patients without disease progression, they may achieve a durable response and facilitate long‐term survival.

Purpose The activity and safety of neoadjuvant nivolumab plus gemcitabine/cisplatin (N+GC) were tested in patients with muscle-invasive bladder urothelial carcinoma (MIBC).Materials and Methods In a prospective phase II trial, patients with cT2-T4a N0 MIBC who were eligible for cisplatin and medically appropriate to undergo radical cystectomy (RC) were enrolled. Treatment with nivolumab 3 mg/kg on days 1 and 15 plus GC (cisplatin 70 mg/m2 on day 1, and gemcitabine 1,000 mg/m2 on days 1, 8, and 15) was repeated every 28 days up to 3 or 4 cycles, depending on the surgery schedules. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (≤ ypT1), disease-free survival (DFS), and safety.Results Between September 2019 and October 2020, 51 patients were enrolled. Neoadjuvant N+GC was well tolerated. Among 49 patients who completed neoadjuvant N+GC, clinical complete response (cCR) was achieved in 59% of intent-to-treat (ITT) population. RC was performed in 34 (69%) patients. pCR was achieved in 24% (12/49) of ITT population and 35% (12/34) of RC patients. Median DFS was not reached. Over a median follow-up of 24 months, 12 patients experienced disease recurrence and were treated with palliative therapy or surgery. Although 12 patients declined surgery and were treated with concurrent chemoradiotherapy, DFS was longer in patients with cCR after neoadjuvant therapy than those without. Preoperative programmed death-ligand 1 (PD-L1) did not correlate with pCR or pathologic downstaging rates.Conclusion Neoadjuvant N+GC was feasible and provided meaningful pathologic responses in patients with MIBC, regardless of baseline PD-L1 expression (ONO-4538-X41; CRIS.nih.go.kr, KCT0003804).

Background: High tumor mutational burden (TMB-H) has been reported as a predictive marker to immunotherapy or prognostic marker in various tumor types. However, there has been little study of the role of TMB-H in advanced biliary tract cancer (BTC). Methods: We analyzed 119 advanced BTC patients who received Gemcitabine/Cisplatin (GP) as a first-line treatment between November 2019 and April 2021. Next-generation sequencing (NGS), including TMB analysis, as a routine clinical practice was performed in 119 patients. The TruSight^TM Oncology 500 assay from Illumina was used as a cancer panel. Results: Among 119 patients, 18 (18.5%) had a tumor with high TMB (≥ 10 Muts/Mb). There were no significant differences between the status of TMB and clinical outcomes with GP, including objective response rate (ORR) ( P = .126), disease control rate (DCR) ( p = .454), and median progression-free survival (PFS) ( p = .599). The median overall survival (OS) was not different between patients with TMB-H and no TMB-H ( p = .430). In subgroup analysis of 32 patients receiving immune checkpoint inhibitor (ICIs), there were significant differences in ORR ( p = .034) and median PFS ( p = .025) with ICIs between patients with and without TMB-H. Conclusions: This study revealed that TMB-H in advanced BTCs did not have a prognostic or role in the standard first-line treatment. However, TMB-H might be a predictive biomarker for response to ICIs in advanced BTC.

Background: Expression of programmed death-ligand 1 (PD-L1) has been reported to correlate with response to immune checkpoint inhibitors (ICIs) in various tumor types. However, there are few data on the role of PD-L1 expression as a predictive and prognostic biomarker of sensitivity to ICIs in patients with advanced biliary tract cancer (BTC). Objectives: We evaluated the role of PD-L1 expression as a predictive and prognostic biomarker of response to ICIs in patients with advanced BTC. Design: We retrospectively analyzed data from 83 advanced BTC patients who received ICIs as second- or third-line treatment between February 2018 and April 2021. Methods: All patient data analysis included evaluation of PD-L1 expression by the combined positive score (CPS). Results: Among 83 patients, 56 (67.5%) had PD-L1 positivity (CPS ⩾ 1). The objective response rate (ORR) to ICIs was significantly higher in advanced BTC patients with PD-L1 expression compared to those without PD-L1 expression (17.8% versus 0%, p = 0.026). However, there were no significant differences in median progression-free survival (PFS; 2.9 versus 2.6 months, p = 0.330) and median overall survival (OS; 8.1 versus 6.3 months, p = 0.289) as a response to ICIs between patients with and without PD-L1 expression. Also, there were no significant differences in ORR, PFS, and OS as a response to ICIs in conjunction with a response to a prior gemcitabine plus cisplatin regimen ( p = 0.654, p = 0.278, and p = 0.302, respectively). Conclusions: The present study suggests that the expression of PD-L1 alone was not sufficient as a novel marker to select advanced BTC patients who might benefit from ICIs. Additional comprehensive studies of biomarkers that can assist in predicting BTC patient responses to pembrolizumab and/or nivolumab therapy are required.

Kim H, et al. J Gastric Cancer. 2025 Oct;25:e46. https://doi.org/10.5230/jgc.2025.25.e46

Purpose The impact of epidermal growth factor receptor (EGFR) mutation in locally advanced non-small cell lung cancer (NSCLC) remains controversial. This study was conducted to investigate the clinical outcomes and recurrence patterns after definitive chemo-radiotherapy (CRT) in patients with unresectable stage III non-squamous-cell lung cancer according to EGFR mutation status.Materials and Methods We retrospectively reviewed 604 patients with pathologically confirmed stage III NSCLC who were treated with definitive CRT and were examined for EGFR mutation at Samsung Medical Center, Korea, from January 2013 to December 2018. Among them, we identified 236 patients with stage III non-squamous-cell lung cancer who were treated with definitive CRT and were examined for EGFR mutation status. We analyzed the frequency of EGFR mutation, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and recurrence pattern.Results Among 236 patients, EGFR mutation was detected in 71 patients (30.1%) and the median follow-up duration was 41.7 months. There were no significant differences in PFS (9.9 vs. 10.9 months, p=0.236), and ORR to CRT (93.0% vs. 90.3%, p=0.623) according to EGFR mutation status. However, the EGFR mutant group showed significantly higher recurrence (88.7% vs. 75.2%, p=0.022), distant metastasis (76.1% vs. 61.2%, p=0.036) rates, especially brain (38.0% vs. 12.7%, p < 0.001), and better median OS (59.2 vs. 41.3 months, p=0.037) compared with patients without EGFR mutation.Conclusion Patients with EGFR mutation-positive unresectable stage III non-squamous lung cancer exhibited higher recurrence and distant metastasis rates, especially brain metastasis.