Lung Cancer Clinical Trials Research Articles

Neoadjuvant Therapy and Lung Cancer: Role of Pathologists.

Recent neoadjuvant clinical trials in lung cancer have demonstrated the survival benefits in carefully selected patients. Standardization of the assessment of pathologic response to neoadjuvant therapy in surgically resected specimens is required. To review the current pathology practices in the gross processing and microscopic assessment of surgically resected non-small cell lung carcinoma specimens after neoadjuvant therapy. PubMed publications and experience of the author. Gross processing of the surgically resected lung carcinoma after neoadjuvant therapy needs further refinement and standardization in clinical trials and in a real-world clinical practice. Microscopic assessment of the response includes quantification of viable tumor, necrosis, and stroma. The best approach would be to use a single standardized and most reproducible scoring system. Published studies on gross processing of lung carcinoma specimens in the neoadjuvant setting and microscopic assessment of pathologic response provide a good foundation for the future standardization of pathology practice.

Data set for the reporting of lung cancer: recommendations from the International Collaboration on Cancer Reporting (ICCR).

Lung cancer is the leading cause of cancer related deaths worldwide, although some patients with early-stage disease can be cured with surgical resection. Standardised reporting of all clinically relevant pathological parameters is essential for best patient care and is also important for ongoing data collection and refinement of important pathological features that impact patient prognosis, staging and clinical care. Using the established International Collaboration on Cancer Reporting (ICCR) procedure, a representative international expert panel of nine lung pathologists as well as an oncologist was convened. Essential core elements and suggested non-core elements were identified for inclusion in the resected lung cancer pathology data set based on predetermined levels of evidence as well as consensus expert opinion. A lung cancer histopathology reporting guide was developed that includes relevant clinical, macroscopic, microscopic and ancillary testing. Critical review and discussion of current evidence was incorporated into the new data set including changes from the 2021 World Health Organisation (WHO) Classification of Thoracic Tumours, fifth edition, new requirements for grading invasive non-mucinous adenocarcinomas, assessment of response to neoadjuvant therapy and requirements for molecular testing in early-stage resected lung carcinomas. This ICCR data set represents incorporation of all relevant parameters for histology reporting of lung cancer resection specimens. Routine use of this data set is recommended for all pathology reporting of resected lung cancer and it is freely available worldwide on the ICCR website (https://www.iccr-cancer.org/datasets/published-datasets/). Widespread implementation will help to ensure consistent and comprehensive pathology reporting and data collection essential for lung cancer patient care, clinical trials and other research.

Bedside to bench and back again-translational research in interventional pulmonology.

Translational research in Interventional Pulmonology has made significant advances in recent years, ranging from novel biomarkers and imaging to practice-changing clinical trials in lung cancer and pleural disease. This review article aims to summarize key research studies in the field to understand the latest published evidence and to highlight areas of growing academic interest. In lung cancer, the role of novel imaging and biomarkers and their potential utility in early lung cancer diagnosis will be highlighted. In pleural disease, less invasive/conservative treatment in pneumothorax, early aggressive treatment in pleural infection along with novel biomarkers, and the shift beyond drainage strategies in malignant pleural effusion and mesothelioma will be discussed. This overview of translational research in the field of interventional pulmonology will ultimately help to highlight the gaps in current evidence to promote research in areas of clinical significance.

EP.06B.18 Biomarker Landscape of Antibody-Drug Conjugates and Bispecific Antibodies in Clinical Trials for Lung Cancer

EP.06B.18 Biomarker Landscape of Antibody-Drug Conjugates and Bispecific Antibodies in Clinical Trials for Lung Cancer

Participation in Non-small Cell Lung Cancer Clinical Trials in the United States by Race/Ethnicity

IntroductionDespite efforts by Cancer Centers and community organizations to increase diversity in clinical trials, significant racial/ethnic disparities remain. Given the high mortality rates in non-small cell lung cancer (NSCLC), it is important to increase diversity in NSCLC trials, ensuring all patients benefit from advances in new treatment modalities. Materials and MethodsWe evaluated the distribution of racial/ethnic minority enrollment in NSCLC clinical trials using data from ClinicalTrials.gov. We extracted trial characteristics, including start year, study phase, tumor stage, sample size, sponsor, geographic region, and masking. The number of participants by race/ethnicity was obtained from ClinicalTrials.gov or linked publications. Using annual NSCLC incidence data from SEER*Stat for each racial/ethnic group from 2010 to 2019, we applied a 2-sample test for equality of proportions with continuity correction to assess differences between incidence and trial participation. ResultsA total of 147 unique studies were included in the final analysis. Of the 28,540 participants, 79.6% were White, with 3% Black, 10.4% Asian or Pacific Islander and 3.4% Hispanic/Latino. Most participants were enrolled in phase III trials (63.8%), industry-sponsored (93.9%), and open-label (67.7%). Black patients were more commonly enrolled in academic sponsored trials and less commonly enrolled in masked (i.e., blinded) studies. When comparing trial participation to annual incidence data, we observed underrepresentation among Black participants (Difference: −7.9%) and Hispanic/Latino participants (Difference: −3.2%). ConclusionPersistent underrepresentation exists in NSCLC clinical trials among Black and Hispanic/Latino patients. We urge further investigation of these findings through well-designed clinical trials among diverse patient populations.

Exploring Demographic Representation and Reporting in Lung Cancer Clinical Trials with Canadian Sites from 2013 to 2023.

This review evaluates the reporting of demographic characteristics and the diversity of participants of phase III lung cancer clinical trials with Canadian research sites. A literature search was conducted using the ClinicalTrials.gov registry to identify clinical trials conducted between 1 January 2013, and 31 December 2023. The demographic reporting practices and the representation of sex/gender, racial, and ethnic groups were assessed. The location of Canadian research sites was also examined for trends in reporting and representation. Associated publications were reviewed for demographic data collection methods. Of the 25 clinical trials, 24 reported race and 18 also reported ethnicity. All clinical trials reported sex/gender, and the city and province of the participating Canadian sites. Most participants were White (66.1%), identified as not Hispanic or Latino (81.4%), and were male (57.8%). The provinces with the most clinical trial sites were Ontario (43.6%) and Quebec (34.2%). Lung cancer clinical trials lack adequate demographic reporting and representation of females, diverse patient groups, and geographical locations in Canada with high lung cancer incidence rates. Specifically, the Indigenous Peoples of Canada and Nunavut require better representation in lung cancer clinical trials conducted in Canada. These findings highlight the need to improve diversity and demographic representation in clinical research.

Gender, Race, and Ethnicity in Lung Cancer Clinical Trial Participation: Analysis of 253,845 Patients From 2002 – 2021

Lung cancer remains the largest cause of cancer-related death, and multiple large studies have identified persistent racial disparities in lung cancer outcomes. In this study, we utilize public recording of lung cancer data on clinicaltrials.gov to sample age, gender, racial, and ethnic characteristics of participants in lung cancer clinical trials. Clinicaltrials.gov, a US federal government repository of clinical trials was queried for the term "lung cancer" and several other related terms. A list of all studies matching these criteria was generated and information regarding age, gender, ethnicity, and racial breakdown of participants was analyzed. Studies that did not report results to clinicaltrials.gov or had at least one non-US site were excluded. Hypothesis testing was performed with Student's T-test and Chi-squared testing. Trends were analyzed using Spearman testing in Python (VS Code, Microsoft, Redmond, WA 2023) RESULTS: Rates of minority (non-white) and female participation in US lung cancer clinical trials have exhibited a significant increase (p<0.01) over the last 20 years (2002-2021, Figures 1) but still do not represent parity with lung cancer incidence. Subset analysis by offered intervention did not show a significant difference between studies that offered surgical or non-invasive intervention in race, gender, or ethnic participation. NIH-funded studies do not appear to have recruited any Hispanic participants as assessed by reporting on clinicaltrials.gov. The rates of race and ethnicity reporting have also significantly increased over the last 20 years (Figure 1C). Our data demonstrate that there are persistent but improving racial and ethnic disparities in lung cancer clinical trials. Limitations of this study include poor reporting of results on clinicaltrials.gov. These findings demonstrate significant progress in the recruitment of minority participation, but also identify a significant role for policy changes to align participation with lung cancer incidence.

Assessing the Uptake of the Lung Cancer Core Outcome Set: A Cross-Sectional Analysis

IntroductionA core outcome set (COS) helps standardize outcome measurements across clinical trials. Although lung cancer is the leading cause of cancer-related deaths, research exploring COS implementation across lung cancer trials remains limited. We aim to analyze the uptake of the lung cancer COS and identify potential gaps in COS adherence. MethodsOn June 26, 2023, we conducted a cross-sectional analysis of clinical trials that evaluated lung cancer interventions. Our sample consisted of studies registered on ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform between September 2011 and June 2023. In a masked and duplicate fashion, investigators extracted data regarding trial characteristics and COS adoption. An interrupted time series analysis was conducted to evaluate the adherence of lung cancer COS before and after its publication. ResultsOf the 626 observed trials, we found no overall significant difference in lung cancer COS uptake pre- and post-publication (0.01%, 95% confidence interval: −0.16% to 0.19%, p = 0.85). The most frequently measured outcomes were “overall survival” (91.69%%) and “treatment-related mortalities” (54.69%). Health-related quality of life questionnaires were typically used to evaluate outcomes in the “Degree of health” domain (49.20%). Outcomes related to “time from diagnosis to treatment” (0%), “place of death” (0.16%), and “duration of time spent in the hospital at the end of life” (1.60%) were rarely measured. ConclusionsDespite the advantages of COS implementation, adherence across lung cancer clinical trials remains alarmingly low—which could compromise data reliability and patient care. Our findings showcase these inconsistencies and emphasize the need for proactive approaches to improve uptake.

Research trends in lung cancer and the tumor microenvironment: a bibliometric analysis of studies published from 2014 to 2023.

Lung cancer (LC) is one of the most common malignant tumors in the world and the leading cause of cancer-related deaths, which seriously threatens human life and health as well as brings a heavy burden to the society. In recent years, the tumor microenvironment (TME) has become an emerging research field and hotspot affecting tumor pathogenesis and therapeutic approaches. However, to date, there has been no bibliometric analysis of lung cancer and the tumor microenvironment from 2014 to 2023.This study aims to comprehensively summarize the current situation and development trends in the field from a bibliometric perspective. The publications about lung cancer and the tumor microenvironment from 2014 to 2023 were extracted from the Web of Science Core Collection (WoSCC). The Microsoft Excel, Origin, R-bibliometrix, CiteSpace, and VOSviewer software are comprehensively used to scientifically analyze the data. Totally, 763 publications were identified in this study. A rapid increase in the number of publications was observed after 2018. More than 400 organizations published these publications in 36 countries or regions. China and the United States have significant influence in this field. Zhou, CC and Frontiers in Immunology are the most productive authors and journals respectively. Besides, the most frequently cited references were those on lung cancer pathogenesis, clinical trials, and treatment modalities. It suggests that novel lung cancer treatment models mainly based on the TME components, such as cancer-associated fibroblasts (CAFs) may lead to future research trends. The field of lung cancer and the tumor microenvironment research is still in the beginning stages. Gene expression, molecular pathways, therapeutic modalities, and novel detection technologies in this field have been widely studied by researchers. This is the first bibliometric study to comprehensively summarize the research trend and development regarding lung cancer and tumor microenvironment over the last decade. The result of our research provides the updated perspective for scholars to understand the key information and cutting-edge hotspots in this field, as well as to identify future research directions.

ASO Author Reflections: Getting a Seat at the Table-A Call for Equitable Inclusion of Women in Lung Cancer Clinical Trials.

ASO Author Reflections: Getting a Seat at the Table-A Call for Equitable Inclusion of Women in Lung Cancer Clinical Trials.

PP01.122 Inclusion of Patients with Brain Metastases and Leptomeningeal Disease in Phase 3 Lung Cancer Clinical Trials: Time for Action

PP01.122 Inclusion of Patients with Brain Metastases and Leptomeningeal Disease in Phase 3 Lung Cancer Clinical Trials: Time for Action

MSR3 Cough, Dyspnea, Chest Pain or a Composite? Analysis of Key Symptoms in Metastatic Non-Small Cell Lung Cancer (mNSCLC) Clinical Trials

MSR3 Cough, Dyspnea, Chest Pain or a Composite? Analysis of Key Symptoms in Metastatic Non-Small Cell Lung Cancer (mNSCLC) Clinical Trials

Investigating disparities in enrollment of patients in lung cancer clinical trials that led to FDA approval for immunotherapies between 2015 and 2023: A comparison with the US population.

e23104 Background: Registrational clinical trials have led to the FDA approval of numerous immunotherapy (IO) agents in the treatment of non-small cell lung cancer (NSCLC) since 2015. Given the historical lack of adequate representation of the US population with cancer in clinical trials, we aimed to analyze disparities in race and ethnicity reporting and enrollment in lung cancer clinical trials that led to FDA-approved immunotherapies between 2015-2023. Methods: The FDA archives and database were queried to review all FDA drug approvals for IO approved to treat NSCLC between 2015 to 2023. Enrollment data were obtained from FDA labels, ClinicalTrials.gov, and corresponding journal manuscripts. The enrollment incidence ratio (EIR) and enrollment mortality ratio (EMR) were calculated as the proportion of patients of a particular race among clinical trial participants in approval studies divided by the estimated proportion of patients of that particular race diagnosed or dying of lung cancer, respectively, among the US population. Results: Among 27 trials with a total of 15,878 subjects, distribution by race shows that 77.5% were White, 16.7% Asian, 8.8% Hispanic, 1.63% Black, 0.33% American Indian Alaska Native (AIAN), and 0.07% were Native Hawaiian and Other Pacific Islander (NHOPI). 67.4% were males while 32.6% were females. The EIR for Non-Hispanic White, Non-Hispanic Black, Asian, and Hispanic patients was 0.99, 0.13, 3.56, and 0.85 respectively. The EMR for Non-Hispanic White, Non-Hispanic Black, Asian, and Hispanic patients was 0.99, 0.12, 4.23, and 0.96 respectively. Racial demographics were reported in 65% of journal manuscripts, 65% of ClinicalTrials.gov pages, and 92% of FDA labels while ethnicity demographics were reported in 0% of journal manuscripts, 42% of ClinicalTrials.gov pages, and 15% of FDA labels. Conclusions: Black, AIAN and female patients are severely underrepresented in lung cancer trials that lead to approval for IO based therapy. Asian patients were overrepresented. Less than half of the trials reported data on ethnicity. Further research is needed to see if regulatory initiatives to increase clinical trial diversity result in more equitable clinical trial enrollment in pivotal trials.

Are the clinical trials in lung cancer an advantage for patients in developing countries?

e20523 Background: Clinical trials are critical to developing new drugs. This study examined the characteristics of patients diagnosed with metastatic non-small cell lung cancer (mNSCLC) and who wanted to participate in clinical trials. This study aims to compare the outcomes of patients who enrolled in clinical trials or not. Methods: The data of the patients who applied to Ankara Yildirim Beyazit University Medical Oncology Department to participate in the first-line treatment-related clinical trials in mNSCLC were retrospectively reviewed. Survival outcomes of patients included in clinical trials (CT) and patients who signed informed consent for clinical trials but could not enroll (standard treatment-ST) were compared. Results: Data from 155 patients who applied to participate in clinical trials were analyzed. Patients who died during the screening process and who lacked systemic treatment information were excluded (n = 14). While 55.3% (n = 78) of the patients participated in the clinical trials, 44.7% (n = 63) could not. Not meeting the inclusion criteria (pathological and clinical) was the most common reason for screen-fail. At a median follow-up of 29 months, median overall survival was 17.1 months (95%CI, 15.1 to 19.1) in the CT group and 9.6 months (95%CI, 7.1 to 12.1) in the ST group (p = 0.015). Median progression-free survival was 11.6 (95% CI, 5.9 - 17.4) and 5.4 (95% CI, 3.7 - 7.2) months, respectively (p = 0.014). Conclusions: Being able to take part in clinical trials is not unfavorable, and it may even improve survival for patients with metastatic non-small cell lung cancer (mNSCLC), particularly in areas of the world where access to novel and effective treatments is limited.

Uptake of recommendations for broadening clinical trial eligibility criteria for patients with brain metastasis and leptomeningeal disease in lung cancer clinical trials: A systematic review.

e23007 Background: Brain metastasis (BM) in patients with lung cancer are relatively frequent (~20%). Clinical trials (CTs) often exclude patients with BM due to concerns about life expectancy, functional status, and toxicity. Restrictive eligibility criteria deter patients with BM from receiving investigational treatments that may be beneficial. In 2017, ASCO, Friends of Cancer Research (FoCR), and the US FDA recommended to expand eligibility criteria to assist in design more representative trials. We examined the uptake of these guidelines in BM/leptomeningeal disease (LMD) inclusion criteria among registered lung cancer CTs. Methods: We extracted eligibility criteria of US-based, phase I/II/III interventional CTs for patients with metastatic lung cancer registered in ClinicalTrials.gov between 10/2012 to 01/2024. CTs registered one year within ASCO/FoCR/FDA published their recommendations were excluded. For each trial, two independent reviewers screened eligibility criteria and classified patients with BM as fully included (active/untreated disease), partially included (treated/stable disease), or excluded, and LMD as included or excluded. Discrepancies were resolved by a third reviewer. Fisher’s exact tests and odds ratio (OR) were obtained by logistic regression. Results: Among 307 CTs, patients with BM were partially included in most CTs (228, 74.3%), excluded in 9 (2.9%) and not mentioned in 35 trials (11.4%). Patients with active BM were included in 35 trials (11.4%). The use of steroids was accepted in 69 trials (22.5%). Only 18 trials (5.8%) included patients with LMD. Most patients with LMD were excluded (135, 44.0%) or not mentioned as criterion (154, 50.2%). A statistically significant difference was observed in the inclusion of patients with BM pre- vs post-recommendations ( p= 0.046). Yet, there was not significant difference in trials with active BM and LMD pre- vs post-recommendations. CTs including patients with active BM or LMD were more likely to appear in CTs explicitly measuring central nervous system outcomes (OR = 4.3; p= 0.002; OR = 14.3; p= 7e-5, respectively). Conclusions: Although existing recommendations to broaden CTs eligibility criteria to include patients with BM showed a significant change, patients with active BM and LMD remained excluded from lung cancer trials. Designing CTs including patients with active BM/LMD is likely to improve patient accrual, increase access to clinical trials and further characterize the investigational drug’s safety and efficacy in this patient population. Exclusion criteria should be clearly justified, and expected toxicity should be reflected in the rationale. As new targeted therapies emerge in lung cancer realm, eligibility criteria should be modernized to fit patients who will be using novel therapies once they are available.

PLWH and lung cancer: A single cancer center experience in Philadelphia, PA.

e20502 Background: Lung cancer has been identified as the leading cause of cancer-related deaths in people living with HIV (PLWH), and disproportionately affects this population independently of smoking status and CD4 count. At the Sidney Kimmel Cancer Center (SKCC) at Jefferson Health, we serve a uniquely underserved patient population of PLWH. As PLWH were categorically excluded from most lung cancer clinical trials, we aim to study the clinical course of our patients with HIV and lung cancer. Methods: A retrospective review of 36 patients within SKCC at Jefferson Health in Philadelphia, PA from 2016 to 2023 were obtained utilizing ICD codes for lung cancer and HIV. Patients who were found to have HIV after their lung cancer diagnosis were excluded. Patient demographics, viral status, antiviral therapy, lung cancer stage, histology, molecular and fusion status, PD-L1 status, form of cancer-directed therapy, date of progression, last date of treatment, and date of death were recorded. Results: Of our 36 patients, 24 (66.7%) were male, and 20 (55.6%) racially identified as Black. 27 patients had NSCLC (20 with adenocarcinoma, 7 with squamous cell carcinoma), and 3 had SCLC. 24 (66.7%) patients had an undetectable viral load at the time of diagnosis and 35 (97.2%) were on antiviral therapy. 32 of 36 patients (88.9%) had advanced stage at the time of diagnosis; 11 had stage III disease (30.6%), and 21 (58.3%) had stage IV disease. Only 4 patients (11.1%) were diagnosed with stage I disease. The mean age of patients at diagnosis was 61.6 years (+/- 8.7 years). Of 18 patients with molecular testing performed, 4 had a KRAS mutation (22.2%) and 1 (5.6%) had a targetable EGFR mutation. Of 16 patients with PD-L1 testing, 7 (43.8%) had 0% expression, 8 (50%) had 1-49% expression, and 1 patient (6.2%) had PD-L1 expression &gt; 50%. The OS among this cohort was 1.3 years (95% CI: 0.8-3.8 years). Conclusions: Our cohort of patients demonstrated more advanced disease at presentation, a younger mean age at diagnosis and poor OS. These trends exist despite the majority of these patients having an undetectable HIV viral load at the time of diagnosis in the setting of ongoing antiviral therapy, indicating a potential relationship between even well-controlled HIV and aggressive lung cancer that warrants further exploration.

Patient-reported outcomes corresponding to most common symptomatic adverse events in lung cancer clinical trials.

11103 Background: FDA recommends assessing the most relevant expected symptomatic adverse events (AEs) with patient-reported outcomes (PROs) in cancer clinical trials (CTs) to complement traditional safety data. To inform selection of symptomatic AEs, we previously identified the most common (i.e., all-grade, clinician-reported in ≥20% of patients) symptomatic AEs from FDA-approved lung cancer product approvals from 2015 through 2021 based on CT monotherapy experimental arm safety data from US Prescribing Information (USPI). The present research aims to assess whether these CTs included PROs which adequately captured common symptomatic AEs. Methods: We assessed 30 CTs that supported lung cancer approvals from 2015 through 2021. We reviewed the study protocol, statistical analysis plan, and/or clinical study report to determine the PRO measures included. We matched symptoms included within PRO measures and items to the most common clinician-reported symptomatic AEs per the USPI to determine the extent to which the PROs and symptomatic AEs corresponded. Results: Twenty-three out of 30 (77%) CTs supporting non-small cell lung cancer (NSCLC) approvals included PRO(s). Nineteen included more than one PRO measure. The most frequently used PRO measures were the European Organisation for Research and Treatment of Cancer-Core Questionnaire (EORTC QLQ-C30; n=19), EORTC-Lung Cancer (EORTC QLQ-L13; n=17), EuroQoL 5-Dimension (EQ-5D; n=12), and selected items from the Patient-reported Outcomes version of the Common Terminology Criteria for Adverse Events item library (PRO-CTCAE; n=4). Nearly all (20 of 23) CTs included PRO items corresponding to more than half of the common symptomatic AEs reported. Symptomatic AEs for types of pain corresponded to general pain PRO items (e.g., “musculoskeletal pain” matched to EORTC item for “pain”). However, PRO items for specific types of pain were not often used. While important symptomatic AEs such as fatigue, diarrhea, nausea, and decreased appetite were often assessed by PROs, others including rash and edema were not usually captured. Ultimately, only 4 of 23 (17%) CTs with PROs included items that assessed all symptomatic AEs that occurred in ≥20% of patients. Of the 4 CTs which included an item library, 3 (75%) comprehensively assessed patient-reported symptomatic AEs, compared to 3 of 19 (16%) CTs that did not employ an item library for patient-reported symptom collection. Conclusions: Based on USPI safety data and PRO measures from CT monotherapy experimental arms of recently approved NSCLC cancer drugs, we determined that while the majority of CTs include PRO items for some relevant symptomatic AEs, other important expected symptomatic AEs (e.g., edema, rash, specific types of pain) were not measured. Future NSCLC CTs should include PRO items for common expected symptomatic AEs which is feasible using well-established PRO item libraries.

Prospective “common arm” comparison of US SWOG S0424 and Japanese JME studies in early-stage non-small cell lung cancer (NSCLC): Survival differences in the context of race, gender and smoking.

8036 Background: In NSCLC, overall frequencies and subtype distribution of EGFR and KRAS mutations differ significantly between Japanese and US patients. In many NSCLC clinical trials, Japanese patient outcomes appear superior to those in western populations. Since 2009, SWOG and Japanese investigators have used the “Common Arm” analytic method to interpret globally-conducted lung cancer clinical trials, providing a mechanism for direct patient-level comparisons in matching trials performed in the US and Japan. S0424 and the Japanese Molecular Epidemiology Study (JME) are large prospective molecular epidemiology studies conducted by SWOG and Japanese investigators and prospectively planned for “Common Arm” analysis. We investigated the effects of mutation distribution on overall survival in early stage NSCLC using data from JME and S0424. Methods: Both studies were designed to accrue representative proportions of ever-smokers (ES) versus never-smokers (NS) in male and female cohorts. Accrual to S0424 was completed in 2011 with 981 pts enrolled (Cheng et al JNCI 2018); JME was completed in 2012 with 957 pts (Kawaguchi et al JCO 2016). A comprehensive questionnaire was used to capture lifestyle, carcinogenic exposures, demographic and clinical data. Five years of follow-up was completed for each study. The association between baseline characteristics and mutation types were analyzed using multivariate logistic regression. The product-limit method was used to estimate overall survival and Cox regression models were fit to estimate hazard ratios. p-values were two-sided and p-values &lt; 0.05 were considered significant. Results: Evaluable pts: 876 for JME; 957 for S0424. Demographic distribution: S0424: 87% Caucasian, 5% Asian, 4% Black; JME: 100% Japanese. As expected, multivariate logistic models adjusting for age, smoking status, gender and BMI showed JME were more likely to have EGFR mutations (p &lt; 0.0001) and less likely to have KRAS mutations (p = 0.02). EGFR mutations were associated with never-smoking (p &lt; 0.0001) and female sex (p &lt; 0.0001); KRAS was associated with smoking (p &lt; 0.0001). Adjusting for age, smoking status and gender, overall survival was greater in JME patients (p &lt; 0.0001,HR = 0.49 (95% CI: 0.40-0.60)). In the subset of pts without an EGFR mutation, survival still favored the JME cohort (p &lt; 0.001, HR = 0.68 (0.53-0.86). Conclusions: Patient level comparison of US (SWOG) and Japanese (JME) patients with early stage NSCLC demonstrated longer survival in Japanese patients even after adjusting for EGFR mutation frequency. Identification of factors that contribute to this finding are under investigation. Female sex remained a risk factor for EGFR mutation-driven disease in both populations. This analysis forms the basis for applying this population-related model in other clinical settings.

Patient-centered perspectives: Examining quality-of-life integration in phase III lung cancer trials (2019-2023).

e23181 Background: In the dynamic landscape of lung cancer treatment, marked by precision medicine advancements, addressing the persistent global health challenge of lung cancer requires nuanced evaluations beyond traditional endpoints like Overall Survival (OS). Aligned with the emphasis on patient-centered care, both the US FDA and ASCO advocate for consistent integration of Quality of Life (QoL) and Patient-Reported Outcomes (PRO). The FDA's 2021 guidance underscores standardized assessment strategies, and ASCO's conceptual framework highlights the pivotal role of QoL and PRO data in elucidating the genuine value of cancer treatment options. This investigation aims to illuminate the extent to which recent trials consider patients' subjective experiences without presupposing an impact on QoL. Methods: This systematic review analyzed PubMed for Phase III lung cancer clinical trials involving anticancer drugs conducted between 2019 and 2023 to assess if QoL was included as an endpoint. Subgroup analyses categorized trials by cancer subtype (e.g., non-small cell lung cancer [NSCLC], small cell lung cancer [SCLC]). Analyses were also stratified by publication year to explore potential temporal trends. The total prevalence of QoL as an endpoint was calculated across all lung cancer subtypes for the entire 5-year period. Subanalyses included impact factor categories (≥ 10 and &lt; 10) and differentiation between superiority and noninferiority trials. Results: The systematic analysis identified 191 Phase III lung cancer clinical trials published between 2019 and 2023, meeting the criteria. QoL was included in 31.93% of trials across all subtypes. Subgroup analyses showed that 33.72% of NSCLC trials incorporated QoL, with variations observed in early-stage resectable disease (26.31%) and unresectable advanced and metastatic cases (34.66%). For SCLC, 19.04% of trials included QoL, with none in the limited stage and 22.22% in the extensive stage. Stratified by publication year, 2019 had 33.33%, 2020 had 39.02%, 2021 had 33.33%, 2022 had 23.33%, and 2023 had 28.94% trials with QoL assessments. Stratification based on impact factor (IF) and trial type revealed 29.4% in Journals ≥10 IF, 35.6% in Journals &lt; 10 IF, 35.5% in superiority trials, and 21.6% in non-inferiority trials. Conclusions: Our analysis reveals a significant shortfall in incorporating QoL as an endpoint. Across all subtypes and stages, a limited percentage of trials included PRO, highlighting a crucial gap in evaluating the comprehensive impact of interventions. The underrepresentation of QoL assessments signals a need for greater attention to the holistic patient experience in lung cancer research. Moving forward, a more standardized and comprehensive integration of QoL assessments in Phase III trials is essential to enhance our understanding of treatment impact and inform more patient-centered care decisions.

Quantitative evaluation of the impact of relaxing eligibility criteria on the risk-benefit profile of drugs for lung cancer based on real-world data.

Restrictive eligibility criteria in cancer drug trials result in low enrollment rates and limited population diversity. Relaxed eligibility criteria (REC) based on solid evidence is becoming necessary for stakeholders worldwide. However, the absence of high-quality, favorable evidence remains a major challenge. This study presents a protocol to quantitatively evaluate the impact of relaxing eligibility criteria in common non-small cell lung cancer (NSCLC) protocols in China, on the risk-benefit profile. This involves a detailed explanation of the rationale, framework, and design of REC. To evaluate our REC in NSCLC drug trials, we will first construct a structured, cross-dimensional real-world NSCLC database using deep learning methods. We will then establish randomized virtual cohorts and perform benefit-risk assessment using Monte Carlo simulation and propensity matching. Shapley value will be utilized to quantitatively measure the effect of the change of each eligibility criterion on patient volume, clinical efficacy and safety. This study is one of the few that focuses on the problem of overly stringent eligibility criteria cancer drug clinical trials, providing quantitative evaluation of the effect of relaxing each NSCLC eligibility criterion. This study will not only provide scientific evidence for the rational design of population inclusion in lung cancer clinical trials, but also establish a data governance system, as well as a REC evaluation framework that can be generalized to other cancer studies.