Metastatic Non-small Cell Lung Cancer Research Articles

EP.06D.04 Prognostic Value of Variant Allele Frequency in Circulating Tumor DNA for Survival Outcomes in Metastatic Non-Small Cell Lung Cancer

EP.06D.04 Prognostic Value of Variant Allele Frequency in Circulating Tumor DNA for Survival Outcomes in Metastatic Non-Small Cell Lung Cancer

P4.11E.27 Comparison of Immunotherapy for Metastatic Non-Small Cell Lung Cancer in Real-World Practice: A Japanese Registry Study

P4.11E.27 Comparison of Immunotherapy for Metastatic Non-Small Cell Lung Cancer in Real-World Practice: A Japanese Registry Study

P4.17D.07 Temporal Improvements in Overall Survival in Metastatic Non-Small Cell Lung Cancer in the United States Since 2004

P4.17D.07 Temporal Improvements in Overall Survival in Metastatic Non-Small Cell Lung Cancer in the United States Since 2004

P2.17A.02 Cost-Efficiency Modeling of Conversion to Biosimilar Bevacizumab-bvzr in Metastatic Non-Small Cell Lung Cancer in Medicare

P2.17A.02 Cost-Efficiency Modeling of Conversion to Biosimilar Bevacizumab-bvzr in Metastatic Non-Small Cell Lung Cancer in Medicare

EP.12A.18 Afatinib vs. Osimertinib as First-Line Treatment for Metastatic Non-Small Cell Lung Cancer Harboring EGFR Mutations

EP.12A.18 Afatinib vs. Osimertinib as First-Line Treatment for Metastatic Non-Small Cell Lung Cancer Harboring EGFR Mutations

Complex Dyslipidemia Induced by Lorlatinib Therapy: A Case Study

ContextLorlatinib is an anaplastic lymphoma kinase (ALK) inhibitor, which is currently used for the treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC). Previous reports have noticed an association between lorlatinib and hyperlipidemia, however the specific mechanisms for this side effect remain unknown. Some investigators have reported nephrotic syndrome to be the underlying cause of lorlatinib-induced hyperlipidemia. Case ReportA 59-year-old female with NSCLC presented with marked elevation of lipid levels, including total cholesterol, triglycerides, low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C), after initiation of lorlatinib therapy. Despite high dose atorvastatin and ezetimibe, lipid levels remained elevated. A 24-hour urine collection revealed only 226 mg of protein excretion. ConclusionsLorlatinib induced a complex dyslipidemia in our patient with elevations of both LDL-C and HDL-C. The underlying mechanism of lorlatinib-induced hyperlipidemia remains unknown and is unlikely to be secondary to nephrotic syndrome in many patients.

P2.07C.04 Surgical Complexity of Anatomical Lung Resections after Induction Immunotherapy for Locally Advanced or Metastatic Non-Small Cell Lung Cancer

P2.07C.04 Surgical Complexity of Anatomical Lung Resections after Induction Immunotherapy for Locally Advanced or Metastatic Non-Small Cell Lung Cancer

P2.11B.02 Genomic Correlates of Response to Chemoimmunotherapy in STK11MUT and KEAP1MUT Metastatic Non-Small Cell Lung Cancer

P2.11B.02 Genomic Correlates of Response to Chemoimmunotherapy in STK11MUT and KEAP1MUT Metastatic Non-Small Cell Lung Cancer

Prognostic significance of bone metastasis and clinical value of bone radiotherapy in metastatic non-small cell lung cancer receiving PD-1/PD-L1 inhibitors: results from a multicenter, prospective, observational study.

Bone metastasis (BoM) is a prevalent occurrence in patients with non-small cell lung cancer (NSCLC), significantly impacting prognosis and diminishing both survival rates and patients' quality of life. More and more studies have demonstrated that immunotherapy can improve the prognosis of NSCLC patients with bone metastases. Previous investigations pertaining to BoM in NSCLC have generally suffered from small sample sizes, absence of propensity score matching (PSM) to equate baseline characteristics, and an omission of the examination of patterns of treatment failure. This study aims to evaluate the prognostic significance of BoM and potential clinical value of bone radiation in metastatic NSCLC patients receiving immunotherapy. Metastatic NSCLC patients receiving programmed cell death protein 1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors from three academic centers were enrolled in a prospective, observational trial (https://clinicaltrials.gov/study/NCT04766515) and those with measurable disease and adequate follow-up were retrospectively reviewed. Propensity score matched (PSM) patients with and without BoM were included in this study. Treatment efficacy, pattern of failure and clinical value of bone radiotherapy were extensively evaluated. A total of 544 out of 1,451 immunotherapy-treated NSCLC patients were included after PSM, including 272 with BoM and 272 without. Patients with baseline BoM had a median progression-free survival (PFS) of 7.8 months [95% confidence interval (CI): 7.0-8.7], lower than those without it (9.5 months; 95% CI: 8.9-10.0) (P<0.001). Patients with baseline BoM had a median overall survival (OS) of 14.5 months (95% CI: 12.6-16.4), lower than those without 27.6 months (95% CI: 25.1-30.1) (P<0.001). Patients with BoM also had lower objective response rate than those without it (11.1% vs. 15.8%, P<0.001). Initial disease progression in the bone was more common in those with BoM (56.5%) compared to those without it (31.7%) (P<0.001). Meanwhile, among patients with BoM, no significant difference of PFS was found between those receiving bone radiation or not, possibly due to a dominant use of palliative radiotherapy. Baseline BoM correlated with worse prognosis and palliative bone radiation did not improve PFS in metastatic NSCLC patients receiving PD-1/PD-L1 inhibitors.

EP.12G.02 Real-World Biomarker Testing and Treatment Patterns for Locally Advanced and Metastatic Non-Small Cell Lung Cancer in Canada

EP.12G.02 Real-World Biomarker Testing and Treatment Patterns for Locally Advanced and Metastatic Non-Small Cell Lung Cancer in Canada

EP.12A.44 Short-course Immunotherapy Prior to Targeted Therapy in EGFR-Mutated Metastatic Non-Small Cell Lung Cancer: A Retrospective Study

EP.12A.44 Short-course Immunotherapy Prior to Targeted Therapy in EGFR-Mutated Metastatic Non-Small Cell Lung Cancer: A Retrospective Study

EP.12A.19 Race May Affect Survival in 1L Patients with Metastatic Non-Small Cell Lung Cancer (mNSLC) Onegfr-Targeted Therapy

EP.12A.19 Race May Affect Survival in 1L Patients with Metastatic Non-Small Cell Lung Cancer (mNSLC) Onegfr-Targeted Therapy

P3.12D.01 A Phase Ib Study of Osimertinib and Tegavivint as First-Line Therapy in Patients with Metastatic EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC)

P3.12D.01 A Phase Ib Study of Osimertinib and Tegavivint as First-Line Therapy in Patients with Metastatic EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC)

EP.12C.04 Location of Metastases and Prognosis of Patients with Metastatic KRAS-Mutant Non-Small Cell Lung Cancer

EP.12C.04 Location of Metastases and Prognosis of Patients with Metastatic KRAS-Mutant Non-Small Cell Lung Cancer

Increasing access to biomarker-driven treatment for lung cancer in Alabama: The Alabama Access initiative.

159 Background: Lung cancer is the leading cause of cancer death in Alabama, with an estimated 2,550 deaths in 2024. Non-small cell lung cancer (NSCLC) represents 85% of these cases. Despite national guidelines recommending comprehensive biomarker testing (CBT) for metastatic NSCLC, significant disparities persist in the utilization of CBT and targeted therapies among Alabama residents. Methods: In March 2024, we launched the "Alabama Access" initiative – a partnership between the LUNGevity Foundation and the O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham – to foster academic and community oncology partnerships to increase access to biomarker-driven treatments. We used a population health science and geospatial mapping approach to visualize oncology practices serving counties with Alabama's highest lung cancer burden. Practices in Walker, Dothan, Marengo, Morgan, Jackson, Marshall, and Montgomery counties were identified as the highest priority based on annual mortality rates. Key interventions will include virtual molecular tumor boards and oncology navigation to facilitate the integration of resources and expertise and ensure that patients in nonacademic practices benefit from the latest advances in precision oncology. After roll-out, we will collect feasibility and acceptability data around program integration. Results: Our analysis revealed that 62.0% of the state’s population resides in Primary Care Health Professional Shortage Areas (HPSAs), and 58 out of 67 counties are classified as Medically Underserved Areas. The poverty rate in 89.6% of counties surpasses the national average, contributing to higher lung cancer incidence and mortality rates, with 62.0% of cases diagnosed at advanced stages. The state also shows a higher smoking prevalence, affecting 97.0% of counties compared to national figures. We will present practice-level testing data, including barriers to CBT. Conclusions: This pilot aims to mitigate disparities in CBT through enhanced collaboration between academic and community oncology settings. Integrating molecular navigation into community practices will be pivotal in disseminating program information and collecting data on current testing practices to improve overall lung cancer care quality in Alabama.

Cost-effectiveness Analysis of Tumor Treating Fields Therapy Combined With Immune Checkpoint Inhibitor in Metastatic Non-small-cell Lung Cancer

BackgroundThe LUNAR clinical trial revealed that incorporating Tumor Treating Fields (TTFields) therapy alongside immune checkpoint inhibitor (ICI) significantly prolonged the overall survival of patients with metastatic, platinum-resistant non-small-cell lung cancer (NSCLC). However, the cost of TTFields therapy is high and may further increase the financial burden for patients. Our research aims to evaluate the cost-effectiveness of TTFields therapy addition with ICI for metastatic NSCLC. MethodsWe constructed a Markov model to evaluate the healthcare costs associated with TTFields therapy combined with ICI for the treatment of advanced NSCLC. In this model, the clinical data utilized came from the LUNAR trial, while drug costs and health state utility values were extracted from public databases and relevant scholarly publications. The major outcomes incorporated costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). ResultsCompared with ICI therapy alone, ICI combination with TTFields therapy resulted in 0.42 QALYs at the cost of $167,329, with an ICER of $398,402.38 per year. The calculated ICER surpassed the generally accepted US willingness-to-pay (WTP) threshold of 150,000 per QALY. One-way sensitivity analyses demonstrated that the utility of progression disease is the most influential factor, followed by the cost of TTFields therapy, the utility of progression-free survival, the cost of ICI, and the cost of adverse events in TTFields therapy combined with ICI. Only when the cost of TTFields therapy is reduced by approximately 80.48%, it would be cost-effective within the commonly accepted WTP threshold of $150,000/QALY. ConclusionsAccording to the US WTP, the combination of TTFields therapy with ICI does not currently represent a cost-effective strategy for metastatic NSCLC followed progression on platinum-resistant therapy. Considering its promising clinical outcomes for metastatic NSCLC, it is necessary to control the expenses of this therapeutic strategy in future applications.

Stem-like exhausted CD8 T cells in pleural effusions predict improved survival in non-small cell lung cancer (NSCLC) and mesothelioma.

Anti-tumor CD8 T cells are important for immunity but can become 'exhausted' and hence ineffective. Tumor-infiltrating exhausted CD8+ T cells include less differentiated stem-like exhausted T (Texstem) cells and terminally exhausted T (Texterm) cells. Both subsets have been proposed as prognostic biomarkers in cancer patients. In this study, we retrospectively investigated their prognostic significance in patients with metastatic non-small cell lung cancer (NSCLC) and validated our findings in a mesothelioma cohort. Pre-treatment malignant pleural effusions (PEs) from 43 NSCLC (41 non-squamous, 2 squamous) patients were analyzed by flow cytometry. The percentages of Texstem and Texterm CD8 T cells were correlated with overall survival (OS) after adjusting for clinicopathological variables. Findings were validated using a mesothelioma cohort (n=49). Mass cytometry was performed on 16 pre-treatment PE samples from 5 mesothelioma and 3 NSCLC patients for T-cell phenotyping. Single-cell multi-omics analysis was performed on 4 pre-treatment PE samples from 2 NSCLC patients and 2 mesothelioma patients for analysis of the transcriptomic profiles, surface markers and T cell receptor (TCR) repertoire. Higher frequency of Texstem was associated with significantly increased OS [median 9.9 vs. 3.4 months, hazard ratio (HR) 0.36, 95% CI: 0.16-0.79, P=0.01]. The frequency of Texterm was not associated with OS. These findings were validated in the mesothelioma cohort (high vs. low Texstem, median OS 32.1 vs. 19.8 months, HR 0.31, 95% CI: 0.10-0.96, P=0.04). Detailed single-cell sequencing and mass cytometry profiling revealed that exhausted T cells from NSCLC expressed greater stem-likeness and less inhibitory markers than those from mesothelioma and that Texstem cells also contained 'bystander' virus-specific T cells. This study demonstrates that PE CD8 Texstem cell abundance is associated with better survival outcomes, and thus may be a useful prognostic biomarker.

Patient-reported outcomes in patients with metastatic non-squamous non-small cell lung cancer from the randomized Phase II PERLA trial comparing first-line chemotherapy plus dostarlimab or pembrolizumab

BackgroundPERLA (NCT04581824) compared efficacy and safety of dostarlimab (DCT) or pembrolizumab (PCT) plus chemotherapy as first-line treatment for metastatic non-small cell lung cancer. Here, we report patient-reported outcomes (PROs; exploratory analysis) from PERLA. MethodsPatients were randomized 1:1 to receive DCT or PCT every 3 weeks (Q3W) for ≤ 35 cycles [C]. PROs (EORTC QLQ-C30 and QLQ-LC13, PRO-CTCAE, FACT-GP5) were collected at baseline, Q3W until C4, Q9W until C16, Q12W until end of treatment and at 30-day safety follow-up. Change from baseline and time to deterioration (TTD) in QLQ-C30 and QLQ-LC13 were analyzed using longitudinal mixed models and Kaplan–Meier estimators, respectively. ResultsThe PRO (DCT/PCT) datasets included 102/99 patients for QLQ-C30, 96/90 for QLQ-LC13, 96/88 for PRO-CTCAE, and 95/87 for FACT-GP5. Completion rates were > 80 % to C4, then decreased in both arms. For QLQ-C30 and QLQ-LC13, most patients reported stable/improved responses at C13 (∼ 9 months on treatment), with similar responses between arms except more patients reported improvements in dyspnea (QLQ-C30: 36.4 % vs 13.0 %; QLQ-LC13: 40.6 % vs 25.0 %) and chest pain (QLQ-LC13: 34.4 % vs 10.0 %) with DCT vs PCT. TTD per QLQ-C30 and QLQ-LC13 were similar between arms, although TTD in dyspnea was longer with DCT vs PCT (QLQ-LC13: 4.24 vs 1.54 months; p = 0.0168). Most patients in both arms reported that adverse events occurred occasionally/rarely/never with moderate/mild severity. Overall, patients reported little/no bother from treatment side effects. ConclusionsDCT maintained health-related quality of life similarly to PCT and was well tolerated, supporting the PERLA primary results and dostarlimab use in future regimens.

Healthcare resource utilization and associated cost in patients with metastatic non-small cell lung cancer treated in the immunotherapy era.

Treatment approach for metastatic non-small cell lung cancer (mNSCLC) has revolutionized in the recent decade with the introduction of immunotherapy and targeted medications in first-line (1L) therapy. We present real-world data on clinical outcomes and direct healthcare resource utilization (HCRU) and cost in a 2.7-million-member Israeli health provider. Newly diagnosed mNSCLC patients between January 2017 and December 2020 were categorized by 1L treatment: platinum-based chemotherapy, targeted therapy, or immunotherapy. HCRU and costs were calculated based on the Ministry of Health Prices and were assessed at a minimum of 6 months' follow-up (cutoff: 30 June 2021). A total of 886 patients were included in the study: 40.6% female, median age 68 years (IQR 61-74), 24.3% never smokers, 80.6% with adenocarcinoma, and 54% with a 0-1 performance status. The median follow-up was 27.12 months (95% CI, 24.7-29.6) and the median duration of first-line (1L) treatment was 2.3 months for platinum-based chemotherapy (n = 177), 12.3 months for targeted therapy (n = 255), and 4.8 months for immunotherapy (n = 463). The median overall survival was 9.09, 27.68, and 12.46 months, respectively. Total 1L costs were driven by radiotherapy for platinum-based chemotherapy and medication for targeted therapy or immunotherapy. Total costs for deceased patients over the entire follow-up were €121 155, €129 458, and €110 716, respectively. The treatment of mNSCLC carries a high economic burden, primarily driven by first-line therapy, especially with targeted and immune therapies. Further studies are needed to evaluate the impact of innovative treatments on the disease management costs of mNSCLC.

Safety and efficacy of consolidative stereotactic radiotherapy for oligo-residual EGFR-mutant non-small cell lung cancer after first-line third-generation EGFR-tyrosine kinase inhibitors: a single-arm, phase 2 trial

Prospective data is limited on the efficacy and safety of consolidative stereotactic radiotherapy (SRT) in metastatic epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients harboring oligo-residual disease (ORD) after first-line third-generation EGFR-tyrosine kinase inhibitors (TKIs). In this single-arm, phase II trial, 61 patients from two academic centers were enrolled from March 2021 to March 2023. All these patients had metastatic EGFR-mutant NSCLC and harbored ORD after first-line third-generation EGFR-TKIs. Consolidative SRT was performed and EGFR-TKIs were not held during SRT. The primary endpoint was progression-free survival (PFS) and the secondary endpoints included overall survival and treatment-related adverse events (TRAEs). A prespecified propensity score matched (PSM) comparison was conducted with a contemporary cohort of patients who developed ORD but received EGFR-TKIs alone. This trial was registered with ClinicalTrails.gov, NCT04764214. All patients received consolidative SRT. With a median follow-up of 21.1 months, the median PFS was 29.9 (80% CI 22.4-32.4) months and the lower boundary exceeded the predefined threshold, meeting the primary endpoint. TRAEs occurred in 43 (70%) patients, with pneumonitis (27.9%) and esophagitis (26.2%) being the most common toxicities. Four patients (6.6%) reported grade ≥3 TRAEs, each for pneumonitis, esophagitis, leukopenia, and cranial radiation necrosis. PSM analysis showed significantly prolonged PFS in EGFR-TKI+SRT group compared to EGFR-TKI group (HR 0.46, 80% CI 0.20-0.61; p=0.002). Consolidative SRT is associated with an encouraging PFS in first-line third-generation EGFR-TKI-treated metastatic NSCLC patients harboring ORD, with generally acceptable toxicities. Further confirmatory studies are warranted. Hui Lan Public Welfare and the Chinese Society of Clinical Oncology Foundation.