Activity of Brigatinib in Patients With Crizotinib-Resistant ALK-positive Non-Small-Cell Lung Cancer According to ALK Fusion and Mutation Status.

Background: Brigatinib, a selective ALK inhibitor, demonstrated preclinical activity against a range of crizotinib-resistant ALK alterations in NSCLC. We examined associations between brigatinib efficacy and tumor- and plasma-detected driver mutations in crizotinib-resistant ALK fusion-positive NSCLC.

Patients And Methods: Tumor tissue and plasma circulating tumor DNA (ctDNA) from patients with crizotinib-exposed ALK-positive NSCLC receiving brigatinib in phase 1/2 and phase 2 ALTA trials were analyzed by next-generation sequencing.

Thymomas and Thymic Carcinomas, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology.

Thymomas and thymic carcinomas are rare mediastinal tumors that originate in the thymus. Patients with thymoma may experience symptoms associated with autoimmune paraneoplastic diseases (such as myasthenia gravis), which typically do not occur in patients with thymic carcinoma. The NCCN Guidelines for Thymomas and Thymic Carcinomas provide guidance for the diagnosis, treatment, and surveillance of patients with thymoma and thymic carcinoma.

Determinants of 5-year survival in patients with advanced NSCLC with PD-L1≥50% treated with first-line pembrolizumab outside of clinical trials: results from the Pembro-real 5Y global registry.

Background: Pembrolizumab monotherapy is an established front-line treatment for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS)≥50%. However, real-world data on its long-term efficacy remains sparse.

Methods: This study assessed 5-year outcomes of first-line pembrolizumab monotherapy in a large, multicenter, real-world cohort of patients with advanced NSCLC and PD-L1 TPS≥50%, referred to as Pembro-real 5Y.

Phase II Trial of Afatinib in Patients With -Mutated Solid Tumors Excluding Lung Cancer: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol A.

Purpose: National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) was a multicohort phase 2 trial that assigned patients with advanced pretreated cancers to molecularly targeted therapies on the basis of tumor genomic testing. NCI-MATCH Arm A evaluated afatinib, an EGFR tyrosine kinase inhibitor (TKI) approved for advanced non-small cell lung cancer, in patients with tumors other than lung cancer harboring mutations.

Methods: Patients with advanced pretreated cancers other than lung cancer found to have selected actionable mutations were offered participation in Arm A.

Lifileucel, an Autologous Tumor-Infiltrating Lymphocyte Monotherapy, in Patients with Advanced Non-Small Cell Lung Cancer Resistant to Immune Checkpoint Inhibitors.

In this phase 2 multicenter study, we evaluated the efficacy and safety of lifileucel (LN-145), an autologous tumor-infiltrating lymphocyte cell therapy, in patients with metastatic non-small cell lung cancer (mNSCLC) who had received prior immunotherapy and progressed on their most recent therapy. The median number of prior systemic therapies was 2 (range, 1-6). Lifileucel was successfully manufactured using tumor tissue from different anatomic sites, predominantly lung.

ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts.

Unlabelled: The majority of EGFR mutant lung adenocarcinomas respond well to EGFR tyrosine kinase inhibitors (TKI). However, most of these responses are partial, with drug-tolerant residual disease remaining even at the time of maximal response. This residual disease can ultimately lead to relapses, which eventually develop in most patients.

Co-Occurring Alterations in Multiple Tumor Suppressor Genes Are Associated With Worse Outcomes in Patients With EGFR-Mutant Lung Cancer.

Introduction: Patients with metastatic EGFR-mutant NSCLC inevitably have disease progression while on tyrosine kinase inhibitor (TKI) therapy. Co-occurring tumor suppressor gene (TSG) alterations have been associated with poor outcomes, however, detailed analyses of their impact on patient outcomes are limited.

Methods: Patients with EGFR-mutant NSCLC treated with EGFR TKIs who had tumor genomic profiling were included.

Mesothelioma: Peritoneal, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM.

Autologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment.

Background: Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as well as inter-person germline and somatic variation. To address these gaps, we developed an autologous system that models the tumor microenvironment (TME) from individual patients with solid tumors.

First-Line Treatment of Driver-Negative Non-Small Cell Lung Cancer.

Immunotherapy-based regimens are an established standard of care for the first-line treatment of driver-negative (EGFR/ALK/ROS WT) advanced non-small cell lung cancer. With multiple immune-based regimens approved in the first-line setting, clinicians are faced in practice with a variety of treatment choices. This article summarizes the most up-to-date trial data on treatments for driver-negative advanced non-small cell lung cancer, including immunotherapy monotherapy, chemoimmunotherapy, and combination immunotherapy, providing a framework for clinicians based on PD-L1 and smoking status.

Quality-of-life outcomes and risk prediction for patients randomized to nivolumab plus ipilimumab vs nivolumab on LungMAP-S1400I.

Background: An important issue for patients with cancer treated with novel therapeutics is how they weigh the effects of treatment on survival and quality of life (QOL). We compared QOL in patients enrolled to SWOG S1400I, a substudy of the LungMAP biomarker-driven master protocol.

Methods: SWOG S1400I was a randomized phase III trial comparing nivolumab plus ipilimumab vs nivolumab for treatment of immunotherapy-naïve disease in advanced squamous cell lung cancer.

Brief Report: Safety and Antitumor Activity of Alectinib Plus Atezolizumab From a Phase 1b Study in Advanced -Positive NSCLC.

Introduction: Alectinib is a preferred first-line treatment option for advanced -positive NSCLC. Combination regimens of alectinib with immune checkpoint inhibitors are being evaluated for synergistic effects.

Methods: Adults with treatment-naive, stage IIIB/IV, or recurrent -positive NSCLC were enrolled into a two-stage phase 1b study.

Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.

Microwave Ablation versus Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer: A Cost-Effectiveness Analysis.

Purpose: To assess the cost effectiveness of microwave ablation (MWA) and stereotactic body radiotherapy (SBRT) for patients with inoperable stage I non-small cell lung cancer (NSCLC).

Materials And Methods: A literature search was performed in MEDLINE with broad search clusters. A decision-analytic model was constructed over a 5-year period.

Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial.

Introduction: In the phase 3 study entitled ALK in Lung cancer Trial of brigAtinib in 1st Line (ALTA-1L), which is a study of brigatinib in ALK inhibitor-naive advanced ALK-positive NSCLC, brigatinib exhibited superior progression-free survival (PFS) versus crizotinib in the two planned interim analyses. Here, we report the final efficacy, safety, and exploratory results.

Methods: Patients were randomized to brigatinib 180 mg once daily (7-d lead-in at 90 mg once daily) or crizotinib 250 mg twice daily.

NTRK1 Fusions identified by non-invasive plasma next-generation sequencing (NGS) across 9 cancer types.

Background: Activating fusions of the NTRK1, NTRK2 and NTRK3 genes are drivers of carcinogenesis and proliferation across a broad range of tumour types in both adult and paediatric patients. Recently, the FDA granted tumour-agnostic approvals of TRK inhibitors, larotrectinib and entrectinib, based on significant and durable responses in multiple primary tumour types. Unfortunately, testing rates in clinical practice remain quite low.

Prolonged Complete Response of Early Stage Primary Adenocarcinoma of the Lung to Nivolumab Monotherapy.

Immune checkpoint inhibitors are currently employed for the treatment of various malignancies, including advanced melanoma and non-small cell lung cancer. As more patients are treated with checkpoint inhibitors, situations will arise in which early-stage disease may be subjected, intentionally or unintentionally, to these agents. This is especially relevant for patients presenting with multiple primary malignant tumors (MPMTs).

Nivolumab Plus Ipilimumab vs Nivolumab for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer: The Lung-MAP S1400I Phase 3 Randomized Clinical Trial.

Importance: Nivolumab plus ipilimumab is superior to platinum-based chemotherapy in treatment-naive advanced non-small cell lung cancer (NSCLC). Nivolumab is superior to docetaxel in advanced pretreated NSCLC.

Objective: To determine whether the addition of ipilimumab to nivolumab improves survival in patients with advanced, pretreated, immunotherapy-naive squamous (Sq) NSCLC.