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Background and Objectives: This study aimed to compare the real-world outcomes of first-line pembrolizumab monotherapy (Mono-IO) versus pembrolizumab plus platinum-based chemotherapy (IO + ChT) in patients with metastatic non-small cell lung cancer (mNSCLC) and a PD-L1 tumor proportion score (TPS) ≥ 50%. Materials and Methods: This retrospective, multicenter, real-world study evaluated 148 patients with mNSCLC and PD-L1 expression ≥ 50% who received either first-line Mono-IO or IO + ChT. Overall survival (OS), progression-free survival (PFS), and clinical benefit rate were compared between the two treatment strategies. Additionally, clinical prognostic factors, patterns of progression, and post-progression treatments were analyzed. Survival outcomes were assessed using Kaplan–Meier estimates, multivariable Cox regression, and restricted mean survival time (RMST) analysis. Results: Patients in the Mono-IO group were significantly older (median 69 vs. 63 years; p < 0.001) and had a higher proportion of ECOG PS 2 (35.3% vs. 5.2%; p < 0.001). No significant differences were observed between Mono-IO and IO + ChT in median OS (32.0 vs. 26.0 months; p = 0.559) or PFS (19.6 vs. 19.4 months; p = 0.572). In an exploratory multivariable analysis adjusting for organ-specific metastases and antibiotic exposure, ECOG PS ≥ 1 (aHR: 1.86, 95% CI: 1.16–2.97; p = 0.009), antibiotic use (aHR: 1.85, 95% CI: 1.16–2.95; p = 0.010), and liver metastasis (aHR: 2.58, 95% CI: 1.16–5.74; p = 0.020) were independent predictors of worse OS. Conversely, PD-L1 TPS ≥ 90% (aHR: 0.56, 95% CI: 0.35–0.91; p = 0.018) was independently associated with superior OS. In exploratory subgroup analysis, a numerical survival trend favoring Mono-IO was observed in patients with PD-L1 TPS ≥ 90%, although this finding remains hypothesis-generating. Following disease progression, 64.7% of patients received no further systemic therapy. Conclusions: In this real-world cohort, no statistically significant differences in OS or PFS were detected between Mono-IO and IO + ChT; however, the wide confidence intervals do not exclude clinically meaningful differences, and equivalence cannot be inferred from these data. PD-L1 TPS ≥ 90% may potentially serve as a biomarker to identify patients who derive benefit from monotherapy, although this exploratory finding requires validation in larger cohorts. Given that the majority of patients did not transition to subsequent therapy in routine practice, likely reflecting multifactorial host frailty and rapid disease evolution, first-line therapeutic optimization warrants careful individualized consideration.

Introductıon: Immune Checkpoint Inhibitors (ICIs) can cause rare but potentially fatal immune-related Adverse Events (irAEs) involving myocarditis, myositis, and Myasthenia Gravis (MG), toxicities with direct neuromuscular and cardiac pharmacological consequences. The burden and outcomes of overlap phenotypes in real-world reports remain incompletely characterized. Methods: We analyzed FAERS (January 2015-September 2025) cancer reports listing at least one ICI as a suspect drug. MedDRA preferred terms identified were ir-myocarditis, ir-myositis, and ir-MG; reports were classified as isolated or overlap (≥ 2 concurrent phenotypes, including Triple M Overlap Syndrome -TMOS). We summarized serious outcomes and time-to-onset. Results: Among 187,347 ICI-associated reports, we identified 3,127 ir-myocarditis, 2,130 ir-myositis, and 1,331 ir-MG cases; 5,142 contained at least one irAE, and 1,151 (22.38%) were overlap. Mortality was highest in ir-myocarditis+ir-MG (43.11%) and TMOS (40.00%); TMOS had frequent life-threatening outcomes (47.46%). Median onset was shorter for overlap (20-22 days) than isolated phenotypes (28-31 days). The anti-PD-1 plus anti-LAG-3 combination had the highest reporting odds of all three irAEs and overlap syndrome. Discussion: In these spontaneous reports, ICI-associated neuromuscular and cardiac overlap was characterised by early onset and high reported mortality. The frequent co-reporting and the poor outcomes recorded in TMOS are compatible with shared immunopathological mechanisms across striated muscle and the neuromuscular junction, although this hypothesis cannot be tested in FAERS. Conclusion: Overlap neuromuscular-cardiac irAEs in FAERS were associated with substantial early mortality and typically occurred within the first 1-2 treatment cycles. Early, low-threshold multidisciplinary evaluation may improve timely recognition. The nivolumab-relatlimab signal warrants dedicated neuromuscular monitoring in patients receiving LAG-3/PD-1 co-blockade.

Data on the clinicopathological features of NRG1 fusion‐positive non‐small cell lung cancer (NSCLC) are limited. We conducted a retrospective, multicenter study and included patients with NRG1 fusion‐positive NSCLC diagnosed between January 2018 and February 2025. Six patients were identified; five were female (83.3%), two were never‐smokers (33.3%), and four were former smokers (66.7%). Adenocarcinoma was the predominant histology ( n = 5), comprising mucinous ( n = 2), enteric ( n = 2), and not otherwise specified ( n = 1) variants, while one patient had squamous cell carcinoma. All were PD‐L1–negative, and CD74‐NRG1 was the most common fusion (50%). Three patients received afatinib; only one achieved a partial response with a progression‐free survival of 8.7 months. Median overall survival was 6.7 months. Our study demonstrates the histologic and molecular heterogeneity of NRG1 fusion‐positive NSCLC, encompassing mucinous and enteric variants of adenocarcinoma. Responses to afatinib were variable, underscoring the need for more effective therapies, including zenocutuzumab and emerging agents.

Second-line chemotherapy is widely used in metastatic urothelial carcinoma after progression on first-line platinum-based therapy, but its independent contribution to survival, as opposed to selection of healthier patients, remains unclear. In this multicenter retrospective cohort of 142 patients treated with first-line platinum-based chemotherapy across seven Turkish centers, overall survival (OS) from first-line progression was compared between patients who received second-line chemotherapy (n = 80) and those who did not (n = 62), using multivariable Cox regression, inverse probability of treatment weighting (IPTW), propensity-score matching, landmark analysis, and a time-dependent Cox model. Median OS was 7.4 versus 4.7 months (log-rank p = 0.064). Second-line chemotherapy was independently associated with improved OS on multivariable analysis (adjusted hazard ratio [aHR] 0.620; 95% confidence interval [CI] 0.423–0.907; p = 0.014); Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2 (aHR 3.881; p = 0.001) and lower albumin (aHR 0.671; p = 0.018) were also independent predictors. The association remained significant after IPTW (HR 0.648; p = 0.025) and after a time-dependent Cox model (HR 0.632; p = 0.019), and was unchanged in ECOG-restricted and Bellmunt-adjusted analyses (p = 0.008, p = 0.029); it narrowly missed significance after propensity-score matching (HR 0.645; p = 0.051) and did not reach significance in the 3-month landmark analysis (HR 0.743; p = 0.180). Power was limited (~49%). In a time-dependent Cox model—the analysis least susceptible to immortal-time bias, as it retains the full cohort and classifies pre-treatment person-time as unexposed—second-line chemotherapy remained independently associated with improved OS (HR 0.632; p = 0.019), closely consistent with the primary multivariable estimate. The conventional Cox, IPTW, and propensity-score-matched analyses, which treat second-line receipt as a baseline exposure, were directionally concordant but share a common time-related bias and are therefore not independent confirmations. ECOG performance status was a consistent predictor throughout.

Perioperative Nivolumab Combined with Neoadjuvant Chemotherapy in Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma - Journal of Oncological Sciences

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Although the STRIDE regimen (durvalumab plus tremelimumab) has demonstrated an overall survival benefit in clinical trials, real-world evidence remains limited, particularly in Turkish clinical practice. This study aimed to evaluate the effectiveness and safety of first-line STRIDE therapy in patients with unresectable HCC treated in routine clinical practice. Methods: We conducted a retrospective multicenter study including patients with unresectable HCC who received first-line durvalumab plus tremelimumab through the Turkish national Early Access Program across 18 oncology centers. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and exploratory Cox regression analyses were performed to evaluate baseline prognostic factors. Results: Thirty-two patients were included. The median PFS was 7.25 months (95% CI, 3.68–22.29), and the median OS was 11.43 months (95% CI, 4.50–not reached). The underlying liver disease etiology was non-viral in 53.1% of patients, hepatitis B virus in 40.6%, and hepatitis C virus in 6.3%. Grade ≥ 3 treatment-related adverse events occurred in fewer than 10% of patients. Conclusions: In this multicenter real-world cohort, first-line durvalumab plus tremelimumab appeared to be a feasible treatment option and was generally well tolerated in patients with unresectable HCC. However, given the retrospective design, small sample size, and absence of a control group, these findings should be interpreted cautiously and require confirmation in larger prospective comparative studies.

Backround:Hepatocellular carcinoma (HCC) is the most common neoplasm to cause death. First line treatment options are still challenging for HCC. STRIDE regimen (durvalumab/tremelimumab) showed improved median overall survival (OS) rates however did not make differ significantly in median progression-free survival (PFS) rate. Method:We reviewed outcomes of patients with HCC who initiated durval-umab/tremelimumab between 2020 and 2024, across 18 institutions. OS and PFS were analyzed using the Kaplan–Meier and Cox models, adjusting for baseline characteris-tics. Results: A total of 32 patients were included in the study. Median PFS was was 7,25 months (%95 confidence interval (CI) 3,68-22,29) and the median OS was 11,43 months (%95 CI 4,5-NA). Non-viral, HBV and HCV constituted to etiology was re-spectively %53,1, %40,6 and %6,3 of patients. Grade ≥ 3 advers events were found less than %10 of populations. Conclusions: This real world retrospective study showed that STRIDE regimen was effective and safety for HCC in first line.