Treatment of Pleural Mesothelioma: ASCO Guideline Update.

Purpose: To provide evidence-based recommendations to practicing physicians and others on the management of pleural mesothelioma (PM).

Methods: ASCO convened an Expert Panel of medical oncology, thoracic surgery, radiation oncology, pathology, cancer genetics, and advocacy experts to conduct an updated literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 2016 through 2024. Outcomes of interest included survival, disease-free or recurrence-free survival, and quality of life.

Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.2.

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Sitravatinib in patients with solid tumors selected by molecular alterations: results from a Phase Ib study.

We report clinical activity and safety of sitravatinib in patients with advanced cancer from basket cohorts with specific molecular alterations, in a Phase Ib study. Patients with advanced solid tumors harboring amplification, mutation, or rearrangement of , , , , , , , or received sitravatinib once daily. Primary end point was confirmed objective response rate (ORR).

Molecular profiling METex14+ non-small cell lung cancer (NSCLC): Impact of histology.

Objectives: MET exon 14 skipping alterations (METex14+) represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) with distinct biological and genomic features. We characterized this heterogeneity in a large cohort, integrating genomic and transcriptomic profiling with clinical outcomes, to elucidate the histologic and molecular traits and survival patterns of METex14+ NSCLC.

Materials And Methods: NSCLC tissue samples (n = 28,739) underwent DNA-based next-generation sequencing (592 genes, NextSeq) or whole-exome sequencing (NovaSeq), RNA-sequencing including whole transcriptome sequencing (WTS, NovaSeq), and PD-L1 IHC (Dako 22C3) at Caris Life Sciences.

Proceedings of the 1st biannual bridging the gaps in lung cancer conference.

Lung cancer is the leading cause of cancer death in the US and globally. The mortality from lung cancer has been declining, due to a reduction in incidence and advances in treatment. Although recent success in developing targeted and immunotherapies for lung cancer has benefitted patients, it has also expanded the complexity of potential treatment options for health care providers.

Randomized trial of anetumab ravtansine and pembrolizumab compared to pembrolizumab for mesothelioma.

Purpose: The mesothelin-targeting antibody-drug conjugate anetumab ravtansine was evaluated in combination with the programmed cell death-1 (PD-1) inhibitor pembrolizumab based on the common expression of mesothelin and reports of activity in mesothelioma.

Patients And Methods: A phase 1 safety run-in of the combination of anetumab ravtansine (6.5 mg/kg iv q3weeks) and pembrolizumab (200 mg, IV q3weeks) was conducted, followed by a phase 2 randomization to the combination or pembrolizumab alone at medical centers across the United States and Canada in the National Cancer Institute's Experimental Therapeutics Clinical Trials Network.

Emerging New Targets in Systemic Therapy for Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is a heterogeneous cancer composed of distinct molecular and pathologic subtypes. Unfortunately, MPM is aggressive, and current therapies for advanced, unresectable disease remain limited to cytotoxic chemotherapy and immunotherapy. Our understanding of the genomic landscape of MPM is steadily growing, while the discovery of effective targeted therapies in MPM has advanced more slowly than in other solid tumors.

ALK Inhibitor Treatment Patterns and Outcomes in Real-World Patients with ALK-Positive Non-Small-Cell Lung Cancer: A Retrospective Cohort Study.

Background: Randomized trials have demonstrated that anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) can be safe and efficacious treatments for patients with ALK-positive advanced non-small-cell lung cancer (aNSCLC). However, their safety, tolerability, effectiveness, and patterns of use in real-world patients remain understudied.

Objective: We sought to assess the overall treatment pattern characteristics, safety, and effectiveness outcomes of real-world patients with ALK-positive aNSCLC receiving ALK TKIs.

Metastatic -amplified non-small-cell lung cancer treated with trastuzumab deruxtecan.

Human epidermal growth factor receptor 2 (HER2) alterations can occur as gene mutations, gene amplification or protein overexpression. DESTINY-Lung01 and DESTINY-Lung02 demonstrated the efficacy of trastuzumab deruxtecan in the subsequent line setting in patients with unresectable or metastatic -mutated non-small-cell lung cancer (NSCLC). Trastuzumab deruxtecan has not been studied in select patients with -amplified NSCLC.

Practical Guidance for the Management of Adverse Events in Patients with KRASG12C-Mutated Non-Small Cell Lung Cancer Receiving Adagrasib.

Adagrasib (MRTX849) is a KRASG12C inhibitor with favorable properties, including long half-life (23 h), dose-dependent pharmacokinetics, and central nervous system (CNS) penetration. As of September 1, 2022, a total of 853 patients with KRASG12C-mutated solid tumors, including patients with CNS metastases, had received adagrasib (monotherapy or in combination). Adagrasib-related treatment-related adverse events (TRAEs) are generally mild to moderate in severity, start early in treatment, resolve quickly with appropriate intervention, and result in a low rate of treatment discontinuation.

Management of toxicities associated with immune checkpoint inhibitors.

Immune-related adverse events (irAEs) encompass a diverse range of toxicities following treatment with immune checkpoint inhibitors (ICIs), each with distinctive symptoms, severities, and outcomes. irAEs can affect any organ and are potentially fatal, so early diagnosis is key in preventing serious events. irAEs can be fulminant, requiring immediate attention and intervention.

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.

Phase I Study Evaluating Glesatinib (MGCD265), An Inhibitor of MET and AXL, in Patients with Non-small Cell Lung Cancer and Other Advanced Solid Tumors.

Background: Heightened signaling by mesenchymal epithelial transition factor (MET) is implicated in tumorigenesis. Glesatinib is an investigational, oral inhibitor of MET and AXL.

Objective: This phase I study determined the maximum tolerated dose (MTD), recommended phase II dose (RP2D), and safety profile of glesatinib in patients with advanced or unresectable solid tumors.

Frequency, underdiagnosis, and heterogeneity of epidermal growth factor receptor exon 20 insertion mutations using real-world genomic datasets.

Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (ex20ins) account for ≤ 12% of all EGFR-mutant nonsmall cell lung cancers. We analysed real-world datasets to determine the frequency of ex20ins variants, and the ability of polymerase chain reaction (PCR) and next-generation sequencing (NGS) to identify them. Three real-world United States NGS databases were used: GENIE, FoundationInsights, and GuardantINFORM.

Real-world observational study of current treatment patterns and outcomes in recurrent or locally advanced/metastatic non-small cell lung cancer.

Background: Treatment for recurrent or advanced/metastatic non-small cell lung cancer (aNSCLC) has advanced in the past 5 years with immunotherapy (IO). This study sought to describe first-line (1L) aNSCLC treatment patterns and clinical outcomes.

Methods: In this retrospective, multisite cohort study, community oncologists reported data for randomly selected stage IIIB/IV, EGFR-/ALK wild-type aNSCLC patients who initiated 1L systemic therapy from 01/01/2016 to 12/31/2019.

Comparative Clinical Outcomes Between EGFR Ex20ins and Wildtype NSCLC Treated with Immune Checkpoint Inhibitors.

Introduction: The activity of immune checkpoint inhibitors (ICIs) in NSCLC harboring EGFR exon 20 insertion mutations (ex20ins) has not been closely examined due to the frequent exclusion of patients with EGFR mutations from large immunotherapy-based NSCLC trials.

Patients And Methods: A real-world, retrospective study was conducted to compare outcomes of ICI-treated patients with EGFR ex20ins and wildtype NSCLC (wt-NSCLC; defined as EGFR and ALK test negative). Patients with advanced NSCLC from the Flatiron Health database (2015-2020) were included in the analysis.