Real-world comparison of the efficacy and safety of atezolizumab versus durvalumab in extensive-stage small cell lung cancer.

Background: Small cell lung cancer (SCLC) is an aggressive disease associated with high relapse rates and limited treatment options. Current standard of care treatment for extensive-stage disease includes combination chemotherapy plus immunotherapy. Programmed death ligand-1 (PD-L1) immune checkpoint inhibitors (ICIs) are preferred first-line treatments in combination with chemotherapy with both atezolizumab and durvalumab being equivalent options.

Discrepancy Between Liquid Biopsy and Tumor Next-Generation Sequencing Due to Low Tumor Fraction in a Patient With Lung Adenocarcinoma.

Tumor next-generation sequencing (NGS) is the gold standard molecular testing for driver genomic alterations in patients with advanced non-small cell lung cancer (NSCLC). However, it requires a biopsy, which is an invasive procedure. In contrast, a liquid biopsy is a minimally invasive test that measures circulating tumor DNA (ctDNA) in the plasma and can be also used for molecular profiling.

Rapid Autopsy to Define Dendritic Cell Spatial Distribution and T Cell Association in Lung Adenocarcinoma.

Immunotherapy response is associated with the presence of conventional dendritic cells (cDCs). cDC type 1 (cDC1) is critically important for CD8+ T cell activation, cDC type 2 (cDC2) regulates CD4+ T cell responses, and mature regulatory cDCs may dampen T cell responses in the tumor microenvironment (TME). However, we lack a clear understanding of cDC distribution in the human TME, cDC prevalence in metastatic sites, and cDC differences in early- versus late-stage disease.

Racial Disparities in Early-Stage NSCLC Treatment: A Call for Action.

Non-small cell lung cancer (NSCLC) is associated with a 5-year survival rate of only 28%; however, when caught at an early stage, it can be cured with surgery or stereotactic body radiotherapy (SBRT). Unfortunately, racial disparities may result in limited access to care for some patients. Liu and colleagues analyzed 64,999 cases of early-stage NSCLC treated between 2005 and 2017 from the Florida Cancer Registry and showed that Black patients had 36% lower odds of receiving curative-intent surgery compared with their White counterparts.

ctDNA for the Evaluation and Management of EGFR-Mutant Non-Small Cell Lung Cancer.

Circulating tumor DNA (ctDNA) offers a new paradigm in optimizing treatment strategies for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). Its potential spans early-stage disease, influencing adjuvant therapy, to advanced disease, where it aids in identifying genomic markers and resistance mechanisms. This review explores the evolving landscape of utilizing liquid biopsies, specifically circulating tumor DNA (ctDNA), in the management of NSCLC with mutations.

Osimertinib afatinib as first-line treatment for patients with metastatic non-small cell lung cancer with an exon 19 deletion or exon 21 L858R mutation.

Background: The optimal treatment sequencing for patients with metastatic epidermal growth factor receptor ()-mutant non-small cell lung cancer (NSCLC) remains a subject of debate. In the United States, osimertinib is the preferred tyrosine kinase inhibitor (TKI) in the first-line setting. However, small retrospective studies suggest that alternative TKI sequencing strategies may produce similar outcomes.

Pre-radiotherapy ctDNA liquid biopsy for risk stratification of oligometastatic non-small cell lung cancer.

The optimal treatment paradigm for patients with oligometastatic non-small cell lung cancer (NSCLC) remains unclear. Some patients with oligometastatic disease experience prolonged remission after locally consolidative radiation therapy (RT), while others harbor micrometastatic disease (below limits of detection by imaging) and benefit from systemic therapy. To risk-stratify and identify the patients most likely to benefit from locally consolidative RT, we performed a multi-institutional cohort study of 1487 patients with oligometastatic NSCLC undergoing liquid biopsy analysis of circulating tumor DNA (ctDNA).

Circulating Tumor DNA Monitoring on Chemo-immunotherapy for Risk Stratification in Advanced Non-Small Cell Lung Cancer.

Purpose: Chemoimmunotherapy (chemoIO) is a prevalent first-line treatment for advanced driver-negative non-small cell lung cancer (NSCLC), with maintenance therapy given after induction. However, there is significant clinical variability in the duration, dosing, and timing of maintenance therapy after induction chemoIO. We used circulating tumor DNA (ctDNA) monitoring to inform outcomes in patients with advanced NSCLC receiving chemoIO.

Phase II Randomized Trial of Carboplatin, Pemetrexed, and Bevacizumab With and Without Atezolizumab in Stage IV Nonsquamous Non-Small-Cell Lung Cancer Patients Who Harbor a Sensitizing EGFR Mutation or Have Never Smoked.

Introduction: Patients with non-small-cell lung cancer (NSCLC) who have never smoked or have tumors with mutations in EGFR generally derive minimal benefit from single-agent PD-1/PD-L1 checkpoint inhibitors. Prior data indicate that adding PD-L1 inhibition to anti-VEGF and cytotoxic chemotherapy may be a promising approach to overcoming immunotherapy resistance in these patients, however prospective validation is needed. This trial in progress (NCT03786692) is evaluating patients with stage IV NSCLC who have never smoked or who have tumors with sensitizing EGFR alterations to determine if a 4-drug combination of atezolizumab, carboplatin, pemetrexed, and bevacizumab can improve outcomes compared to carboplatin, pemetrexed and bevacizumab without atezolizumab.

Genomic approaches to cancer and minimal residual disease detection using circulating tumor DNA.

Liquid biopsies using cell-free circulating tumor DNA (ctDNA) are being used frequently in both research and clinical settings. ctDNA can be used to identify actionable mutations to personalize systemic therapy, detect post-treatment minimal residual disease (MRD), and predict responses to immunotherapy. ctDNA can also be isolated from a range of different biofluids, with the possibility of detecting locoregional MRD with increased sensitivity if sampling more proximally than blood plasma.

ctDNA Monitoring for Small Cell Lung Cancer: Ready for Prime Time?

Small cell lung cancer (SCLC) is the deadliest form of lung cancer and has few precision medicine approaches available. A recent study analyzed circulating tumor DNA (ctDNA) in 33 patients with extensive-stage SCLC and showed that ctDNA levels and response patterns correlate strongly with clinical response and survival outcomes. See related article by Sivapalan et al.

Pre-radiotherapy ctDNA liquid biopsy for risk stratification of oligometastatic non-small cell lung cancer.

The optimal treatment for patients with oligometastatic non-small cell lung cancer (NSCLC) remains unclear. Some patients with oligometastatic disease can experience prolonged remission after locally consolidative radiation therapy (RT), while others harbor micrometastatic disease (below current limits of detection by imaging) that may benefit from further prioritization of systemic therapy. To better risk-stratify this population and identify the patients most likely to benefit from locally consolidative radiation therapy, we performed a multi-institutional cohort study of patients with oligometastatic NSCLC undergoing liquid biopsy analysis of circulating tumor DNA (ctDNA).

Detectable Lipidomes and Metabolomes by Different Plasma Exosome Isolation Methods in Healthy Controls and Patients with Advanced Prostate and Lung Cancer.

Circulating exosomes in the blood are promising tools for biomarker discovery in cancer. Due to their heterogeneity, different isolation methods may enrich distinct exosome cargos generating different omic profiles. In this study, we evaluated the effects of plasma exosome isolation methods on detectable multi-omic profiles in patients with non-small cell lung cancer (NSCLC), castration-resistant prostate cancer (CRPC), and healthy controls, and developed an algorithm to quantify exosome enrichment.

Treatment Strategies for Non-Small Cell Lung Cancer with Common Mutations: A Review of the History of EGFR TKIs Approval and Emerging Data.

The development of targeted therapies over the past two decades has led to a dramatic change in the management of -mutant non-small cell lung cancer (NSCLC). While there are currently five approved EGFR tyrosine kinase inhibitors (TKIs) for treating -mutant NSCLC in the first-line setting, therapy selection after progression on EGFR TKIs remains complex. Multiple groups are investigating novel therapies and drug combinations to determine the optimal therapy and treatment sequence for these patients.

Making the Rounds: Exploring the Role of Circulating Tumor DNA (ctDNA) in Non-Small Cell Lung Cancer.

Advancements in the clinical practice of non-small cell lung cancer (NSCLC) are shifting treatment paradigms towards increasingly personalized approaches. Liquid biopsies using various circulating analytes provide minimally invasive methods of sampling the molecular content within tumor cells. Plasma-derived circulating tumor DNA (ctDNA), the tumor-derived component of cell-free DNA (cfDNA), is the most extensively studied analyte and has a growing list of applications in the clinical management of NSCLC.

Immune Checkpoint Inhibitors and Chemoradiation for Limited-Stage Small Cell Lung Cancer.

Limited-stage small cell lung cancer (LS-SCLC) is a potentially curable disease. However, most patients develop disease relapse shortly after definitive treatment. The landmark trials IMpower133 and CASPIAN demonstrated a survival benefit with the addition of immunotherapy to first-line platinum/etoposide for extensive-stage small cell lung cancer.

Overcoming -Mutant Lung Cancer.

More than 50 years after the discovery of RAS family proteins, which harbor the most common activating mutations in cancer, the U.S. Food and Drug Administration approved the first direct allele-specific inhibitor of mutant in lung cancer.

Circulating Tumor DNA Minimal Residual Disease Detection of Non-Small-Cell Lung Cancer Treated With Curative Intent.

Circulating tumor DNA (ctDNA) minimal residual disease (MRD) is a powerful biomarker with the potential to improve survival outcomes for non-small-cell lung cancer (NSCLC). Multiple groups have shown the ability to detect MRD following curative-intent NSCLC treatment using next-generation sequencing-based assays of plasma cell-free DNA. These studies have been modest in size, largely retrospective, and without thorough prospective clinical validation.

Cancer Detection and Classification by CpG Island Hypermethylation Signatures in Plasma Cell-Free DNA.

Cell-free DNA (cfDNA) methylation has emerged as a promising biomarker for early cancer detection, tumor type classification, and treatment response monitoring. Enrichment-based cfDNA methylation profiling methods such as cfMeDIP-seq have shown high accuracy in the classification of multiple cancer types. We have previously optimized another enrichment-based approach for ultra-low input cfDNA methylome profiling, termed cfMBD-seq.

Commercial ctDNA Assays for Minimal Residual Disease Detection of Solid Tumors.

The detection of circulating tumor DNA via liquid biopsy has become an important diagnostic test for patients with cancer. While certain commercial liquid biopsy platforms designed to detect circulating tumor DNA have been approved to guide clinical decisions in advanced solid tumors, the clinical utility of these assays for detecting minimal residual disease after curative-intent treatment of nonmetastatic disease is currently limited. Predicting disease response and relapse has considerable potential for increasing the effective implementation of neoadjuvant and adjuvant therapies.

A phase II study of everolimus in patients with advanced solid malignancies with or mutations.

Background: Activation of the mTOR pathway has been implicated in the development of several malignancies and alterations in and , can lead to the dysregulation of this pathway. Furthermore, mutations in and are known to confer sensitivity to everolimus-an mTOR inhibitor. Based on these data, a single-arm, open label, single-institution phase II basket study was designed to assess the activity of everolimus in patients with solid malignancies whose tumors harbored mutations in , or .

ctDNA MRD Detection and Personalized Oncogenomic Analysis in Oligometastatic Colorectal Cancer From Plasma and Urine.

Unlabelled: We hypothesized that circulating tumor DNA (ctDNA) molecular residual disease (MRD) analysis without prior mutational knowledge could be performed after neoadjuvant chemotherapy to assess oligometastatic colorectal cancer (CRC) treated surgically with curative intent. We also investigated urine as an alternative analyte for ctDNA MRD detection in this nongenitourinary setting.

Patients And Methods: We applied AVENIO targeted next-generation sequencing to plasma, tumor, and urine samples acquired on the day of curative-intent surgery from 24 prospectively enrolled patients with oligometastatic CRC.

Immunotherapy for Advanced Non-Small Cell Lung Cancer: A Decade of Progress.

The treatment paradigm for patients with advanced non-small cell lung cancer has substantially changed with the discovery of immunotherapy. The incorporation of immunotherapy into treatment algorithms has resulted in better outcomes for patients, with fewer side effects compared with classic chemotherapeutic agents. Multiple treatment options are now available for patients with advanced non-small cell lung cancer, ranging from single-agent immunotherapy to quadruple therapy, which involves dual immune checkpoint inhibitor plus chemotherapy or immune checkpoint inhibitor plus chemotherapy plus anti-vascular endothelial growth factor drugs.