Real-world outcomes and subsequent treatment patterns in patients with advanced non-small cell lung cancer and atypical EGFR mutations receiving first-line osimertinib monotherapy
Nieva JJ, Wang X, Doroshow D, et al. Oncol Ther. 2025. Epub ahead of print.
Summary. Researchers assessed outcomes of first-line osimertinib monotherapy among patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with atypical epidermal growth factor receptor (EGFR) mutations. Fifty-five patients were included for analysis, 20 (36%) of whom harbored compound EGFR mutations or de novo T790M only (Group A) and 35 (64%) of whom harbored atypical EGFR mutations only (Group B). Overall, median time to next treatment or death (TTNTD) and time to treatment discontinuation (TTD) were 12.8 and 10.7 months, respectively. Median real-world progression-free survival (PFS) was 8.8 months, and median overall survival (OS) was 28.5 months in the entire cohort. Group A had longer median TTNTD (28.4 months), TTD (22.3 months), real-world PFS (20.3 months), and OS (42.5 months) compared to Group B (9.2, 6.4, 6.6, and 20.0 months, respectively). Seven patients (13%; 30% from Group A, 3% from Group B) remained on first-line osimertinib at the end of study follow-up. Thirty patients (54%; 40% from Group A, 63% from Group B) discontinued due to death. Subsequent treatment was initiated by 18 patients (33%; 30% from Group A, 34% from Group B), most patients receiving osimertinib combination therapy (n=5, 28%) or chemotherapy (n=4, 22%).
* PMID: 41206837
Simultaneous durvalumab and platinum-based chemoradiotherapy in unresectable Stage III non-small cell lung cancer: the Phase III PACIFIC-2 study
Bradley JD, Sugawara S, Lee KH, et al. J Clin Oncol. 2025;43(33):3610–3621.
Summary. In the Phase III PACIFIC-2 trial, researchers evaluated the efficacy and safety of simultaneous durvalumab plus concurrent chemoradiotherapy (cCRT) followed by consolidation durvalumab in patients with unresectable Stage III NSCLC. Among 328 patients, 219 were randomized to the durvalumab plus cCRT arm and 109 to the placebo plus cCRT arm. Median PFS was 13.8 months in the durvalumab arm and 9.4 months in the placebo arm, though this difference was not significant (hazard ratio [HR]: 0.85, p=0.247). Similarly, median OS was numerically longer with durvalumab versus placebo (36.4 vs. 29.5 months; HR: 1.03, p=0.823). The rate of maximum Grade 3 or 4 adverse events (AEs) was 53.4 percent in the durvalumab arm and 59.3 percent in the placebo arm.
* PMID: 41082707, PMCID: PMC12622289
Interstitial lung disease and risk of lung cancer
Xu H, Yin L, Bian W, et al. JAMA Netw Open. 2025;8(7):e2519630.
Summary. A prospective cohort study using Swedish national registry data found that individuals with interstitial lung disease (ILD) had a significantly elevated risk for lung cancer compared with those without ILD. Over a 30-year follow-up of more than 5.4 million individuals, lung cancer incidence was markedly higher among those with ILD versus those without ILD (355.4 vs. 26.2 per 100,000 person-years). The adjusted HR (aHR) for lung cancer was 2.16, rising to 3.68 in individuals without smoking-related diseases. Sibling-controlled analyses confirmed the association, with an aHR of 2.91 for lung cancer in patients with ILD versus their siblings without ILD. Researchers noted that nongenetic mechanisms might play a dominant role in the observed association and emphasized the need for enhanced screening strategies and smoking cessation counseling in this high-risk population.
* PMID: 40632533, PMCID: PMC12242686
Controlling Nutritional Status (CONUT) score as a predictor of prognosis in non-small cell lung cancer
Pagliaro R, Scalfi L, Di Fiore I, et al. Nutrients. 2025;17(21):3416.
Summary. In this single-center, retrospective, cohort study, researchers evaluated the utility of Controlling Nutritional Status (CONUT) score as a prognostic predictor in NSCLC. Thirty-two patients had a CONUT score of 2 or greater, indicating risk of malnutrition, and 77 patients had a score of 0 or 1. Radiologic response was improved in patients with a low CONUT score; significantly more patients with a low score achieved partial response (25.7%) or stable disease (34.0%) after four cycles of therapy compared to those with a high score (9.2% and 20.2%, respectively). CONUT score was significantly associated with disease progression (HR: 1.72, p<0.001). The 36-month OS rate was 75.8 percent in the high score group compared to 48.4 percent in the low score group. According to multivariable analysis, CONUT score was a significant predictor of PFS and OS (both p=0.004).
* PMID: 41228489, PMCID: PMC12610560
Monitoring lung tumor volume on daily cone beam CT; is it achievable in a real-world setting?
Barrett S, Marignol L, Hanna GG, et al. Tech Innov Patient Support Radiat Oncol. 2025;36:100352.
Summary. Researchers studied the use of semi-automated target volume (TV) delineation on cone-beam computed tomography (CBCT) in 76 patients with NSCLC who underwent radical radiotherapy. A total of 553 scans (CBCT: n=477, average image projection [AVIP]: n=72, 3D planning CT: n=4) were analyzed. A senior radiotherapist adjusted auto-contours, which were then reviewed for accuracy. Minor revisions of the auto-contour were required in 59.1 percent of scans, major revisions in 30.7 percent, and no revisions in 8.1 percent. Median time to adjust auto-contours on CBCT was 83 seconds (range: 0–460 seconds). These findings demonstrate the feasibility of TV delineation on CBCT in this patient population.
* PMID: 41246112, PMCID: PMC12616081
Predicting EGFR gene mutation in lung adenocarcinoma using spectral CT combined with AI parameters: a diagnostic accuracy study
She L, Xie M, Xu G, et al. Front Oncol. 2025;15:1611759.
Summary. In this retrospective study, researchers evaluated the ability of spectral CT and artificial intelligence (AI)–derived parameters in the prediction of EGFR mutation status in lung adenocarcinoma (LUAD). Eighty-nine patients with EGFR mutations and 61 without EGFR mutations were included for analysis. Spectral curve slope (λHU) was significantly higher in the EGFR-mutant group versus the wildtype group (2.51 vs. 2.19, p=0.049). The EGFR-mutant group had significantly larger tumor surface area compared to the wildtype group (28.57cm2 vs. 18.63cm2, p=0.043). Multivariate analysis showed that smoking history (p=0.012), λHU (p=0.015), and tumor surface area (p=0.029) were independent predictors of EGFR mutations. A predictive model including these risk factors showed strong discriminative ability, with an area under the receiver operating characteristic curve (AUC) of 0.713; sensitivity was 0.600, and specificity was 0.754. The calibration curve suggested favorable goodness-of-fit, and decision curve analysis indicated clinical utility.
* PMID: 41244899, PMCID: PMC12611665
Impact of N1 lymph node burden on survival outcomes in nonskip pN2 non-small cell lung cancer
Luo B, Liang S, Zhong L, et al. Lung Cancer. 2025;210:108839. Epub ahead of print.
Summary. In this retrospective analysis, researchers assessed the prognostic impact of N1 lymph node burden in 477 patients with nonskip pN2 NSCLC. High N1 lymph node ratio (LNR) was observed in 48.4 percent of patients, and high N1 lymph node station ratio (LNsR) was observed in 45.3 percent of patients. Kaplan–Meier analysis showed that N1 LNR, N1 LNsR, N1 positive node count, and N1 positive station count were significantly associated with worse disease-free survival (DFS); however, on multivariable analysis, only N1 LNR was a significant independent predictor of poorer DFS (HR: 1.47, p=0.023). N1 burden was not associated with OS on multivariable analysis. Subgroup analyses showed a significant association between high N1 LNR and DFS in the pN2a subgroup (p=0.009).
* PMID: 41242287