Lung cancer is a heterogeneous and complex disease requiring multidisciplinary input for optimal management planning, with guidelines recommending that all patients be discussed in a multidisciplinary setting. Multidisciplinary meeting (MDM) discussion aims to enhance evidence-based management, improve treatment access, and optimize complex management plans. We aimed to assess the extent and impacts of MDM discussion in patients with lung cancer described by the Victorian Lung Cancer Registry from 2011 to 2023 in Victoria, Australia. We identified MDM-presented and nonpresented patients and assessed the impacts of MDM presentation. OR and survival hazard ratios were assessed using Cox proportional regression analysis. Survival analysis was determined using the Kaplan-Meier product-limit method. Sensitivity analyses were conducted using landmark analysis and propensity score matching methods. A total of 18,597 patients were included, of whom 67% had evidence of presentation to a lung cancer MDM, with MDM presentation increasing from 59.1% to 80.6% during the study period. MDM presentation was associated with higher levels of provision of guideline-concordant treatment in NSCLC (56.2% versus 44.5%, p < 0.001), and lower levels of no treatment (10.0% versus 21.4%, p < 0.001). Modifiable factors that could increase MDM presentation include referral of patients of older age, stage IV disease, SCLC, and diagnosis at a private or regional hospital. Propensity-matched survival analysis in NSCLC revealed a median survival of 1.1 years for MDM-presented versus 0.86 years for nonpresented individuals, providing a 12% reduction in mortality hazard (hazard ratio 0.88 [0.82-0.95], p < 0.001). During the period of activity of the Victorian Lung Cancer Registry, MDM presentation increased from 59.1% to 80.6%. Management outcomes in MDM-presented patients identified multiple underserved cohorts and revealed considerable increases in treatment modalities and guideline-concordant treatment in NSCLC in this observational study, with an associated 12% improvement in survival advantage overall.

BackgroundThymic epithelial tumors, including thymomas and thymic carcinomas (TC), are rare thoracic malignancies with poor prognosis in advanced stages. Platinum-based chemotherapy (CT) remains the first-line standard with limited efficacy. Novel systemic therapies, such as immune checkpoint inhibitors (ICIs) and antiangiogenic agents, have exhibited promise in refractory disease.MethodsA systematic search of PubMed, EMBASE, and Cochrane was performed for studies including patients with unresectable, recurrent, or metastatic thymic epithelial tumors treated with platinum-based CT combined with ICIs or antiangiogenic agents. Meta-analyses were conducted using a random-effects model, with heterogeneity assessed through the I2 statistic and Cochran’s Q test.ResultsNine studies encompassing 208 patients were included, of which 93.7% had TC. The data set comprised five phase II trials and four retrospective cohorts. The pooled 12-month overall survival rate was 96.08% (95% confidence interval [CI]: 84.80–99.08), and 12-month progression-free survival was 56.68% (95% CI: 45.82–70.44). The median duration of response and median progression-free survival were 11.96 (95% CI: 6.32–22.64) months and 16.22 (95% CI: 10.30–25.52) months, respectively, with a pooled objective response rate of 57.69% (95% CI: 43.99–70.3). The objective response rate was 68.50% for antiangiogenic and 51.19% for ICIs combinations. Any-grade treatment-related adverse events occurred in 88.65%, grade 3 or higher in 30.22%, and grade 3 or higher immune-related adverse events in 11.62%, with treatment discontinuation in 13.55%.ConclusionPlatinum-based CT combined with ICIs or antiangiogenic agents exhibits promising efficacy and manageable toxicity, particularly in TC. Evidence in thymomas remains limited, and severe immune-related toxicity warrants caution. Randomized trials are needed for confirmation.

IntroductionIn the phase 3 EVOKE-01 trial (NCT05089734), sacituzumab govitecan (SG) exhibited a numerical improvement in overall survival and tolerability compared with docetaxel in patients with metastatic NSCLC previously treated with platinum-based chemotherapy and programmed cell death protein (ligand) 1 inhibitors, although results were not statistically significant. This analysis evaluated health-related quality of life (HRQoL) data from EVOKE-01.MethodsPatients (N = 603) were randomized 1:1 to SG (n = 299) or docetaxel (n = 304) in 21-day cycles. HRQoL was assessed by the NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ), European Organization for Research and Treatment of Cancer Quality of Life questionnaire–Core 30 (QLQ-C30), and EuroQol 5 Dimension 3-level questionnaire. Least square mean changes from baseline at week 25, time to first meaningful deterioration or death, and time to confirmed deterioration were analyzed.ResultsSG exhibited significantly and meaningfully better effects than docetaxel on NSCLC-SAQ shortness of breath (SoB), fatigue, total score, and on QLQ-C30 role functioning, fatigue, and dyspnea. Time to first meaningful deterioration or death favored SG over docetaxel for NSCLC-SAQ SoB (hazard ratio [95% confidence interval ]: 0.75 [0.61–0.91]), fatigue (0.70 [0.57–0.86]), and total score (0.80 [0.66–0.97]); QLQ-C30 fatigue (0.80 [0.66–0.96]) and dyspnea (0.74 [0.60–0.90]); and EuroQol visual analog scale (0.79 [0.65–0.96]). The time to confirmed deterioration favored SG over docetaxel for NSCLC-SAQ SoB (0.59 [0.44–0.77]) and fatigue (0.70 [0.52–0.95]), and QLQ-C30 fatigue (0.75 [0.59–0.95]).ConclusionsThese exploratory results suggest that SG may benefit HRQoL over docetaxel, supporting SG as an active therapeutic agent for metastatic NSCLC post platinum-based and programmed cell death protein (ligand) 1 inhibitor therapy.

BackgroundAlthough most phase III pivotal trials have set the duration of immune checkpoint blockers (ICB) for advanced NSCLC at 2 years, the criteria for safely discontinuing ICB remain undefined. Growing evidence links ICB efficacy to gut microbiota, positioning gut microbial taxonomic profiling as a promising biomarker to guide treatment decisions. We performed a retrospective analysis exploring clinical outcomes and the utility of multiomic decision-making tools in patients with NSCLC at Gustave Roussy who completed 24 months of ICB-based therapy without disease progression (PD).MethodsPatients receiving ICB between July 2016 and January 2023 were identified from the ONCOBIOTICS (NCT04567446) and STING (NCT04932525) study datasets. We selected those who reached 24 months of treatment without disease progression. Clinical characteristics and multiomic assessments, including gut microbiota profiling (TOPOSCORE by whole-genome sequencing), positron emission tomography–18-fluorodeoxyglucose imaging, and circulating tumor DNA, collected at 24 months, were analyzed. Key outcomes included overall survival (OS), progression-free survival (PFS), and PFS rates at 24 months after the completion of 2 years of ICB, stratified by molecular, metabolic, and microbial signatures.ResultsOut of 123 patients treated for at least 18 months, 35 completed 24 months, with 31 eligible for the analysis. Of these, 68% continued ICB, whereas 32% discontinued therapy at the physician’s decision. Clinical characteristics were similar across groups. After a median follow-up of 59.1 months, OS and PFS did not differ significantly between those who discontinued and those who continued treatment (OS p = 0.9012). Among all multiomic tools, gut microbiota composition exhibited a trend (though not statistically significant) association with PFS rates at 24 months after the completion of 2 years of ICB. Patients with a favorable microbiota profile had a higher rate of sustained response at 24 months compared with those with dysbiotic signatures (81% versus 44%, respectively, p = 0.0870).ConclusionsDiscontinuing ICB after 24 months did not negatively impact OS in our real-world cohort. Although limited by the small sample size, these findings support the potential of gut microbiota profiling as a promising tool to guide ICB duration. Integrating a translational multiomic algorithm, in particular microbial signals, may help personalize treatment strategies and safely shorten immunotherapy courses.

IntroductionPERLA is a global, double-blind, phase II trial comparing anti–programmed cell death protein 1 antibodies, dostarlimab, and pembrolizumab in combination with chemotherapy (D+CT and P+CT, respectively) in patients with metastatic nonsquamous NSCLC without actionable genomic aberrations in the first-line setting.MethodsPatients were randomized 1:1 to receive not more than 35 cycles of 500 mg dostarlimab or 200 mg pembrolizumab, with less than or equal to 35 cycles of 500 mg/m2 pemetrexed and less than or equal to 4 cycles of cisplatin (75 mg/m2) or carboplatin (area under the curve 5 mg/mL/min) every 3 weeks. The primary end point was the overall response rate by blinded independent central review. The secondary end points included progression-free survival (PFS) on the basis of investigator assessment, overall survival (OS), and safety. Here, we reported on the long-term OS, PFS, and safety analyses.ResultsAt the end of the study (September 10, 2024), the median follow-up time (mo) for PFS was 30.4 for D+CT and 30.4 for P+CT. The median PFS (mo [95% confidence interval (CI)]) was 8.8 (6.9–11.0) for D+CT and 6.8 (4.9–7.1) for P+CT (hazard ratio 0.77 [95% CI: 0.58–1.03] at 79% maturity). The median follow-up time (mo) for OS was 35.5 for D+CT and 35.2 for P+CT. The median OS (mo [95% CI]) was 20.2 (14.5–27.3) and 15.9 (11.6–19.3), respectively (hazard ratio 0.75 [95% CI: 0.55–1.02] at 70% maturity). Safety profiles were similar between arms and consistent with previous analyses.ConclusionsThis long-term analysis reaffirms previous observations that D+CT exhibited similar efficacy to P+CT and exhibits strong clinical efficacy as a first-line treatment for patients with metastatic nonsquamous NSCLC.Clinical trial registrationNCT04581824.