Novel Approach to Proficiency Testing Reveals Significant Variations in Biomarker Practice Leading to Critical Differences in Lung Cancer Management.

Introduction: Timely access to quality biomarker testing in NSCLC is critical to patient outcomes. The Canadian Pathology Quality Assurance provides external quality assurance (EQA) to laboratories in Canada. The Canadian Pathology Quality Assurance has recently developed a novel approach to molecular biomarker EQA testing, assessing accuracy, turnaround time, and interpretation of reports.

Patterns of Treatment and Real-World Outcomes of Patients With Non-small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations Receiving Mobocertinib: The EXTRACT Study.

Background: Real-world data regarding patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations receiving mobocertinib are limited. This study describes these patients' characteristics and outcomes.

Methods: A chart review was conducted across three countries (Canada, France, and Hong Kong), abstracting data from eligible patients (NCT05207423).

The continually evolving landscape of novel therapies in oncogene-driven advanced non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) is a highly heterogeneous disease that is frequently associated with a host of known oncogenic alterations. Advances in molecular diagnostics and drug development have facilitated the targeting of novel alterations such that the majority of NSCLC patients have driver mutations that are now clinically actionable. The goal of this review is to gain insights into clinical research and development principles by summary, analysis, and discussion of data on agents targeting known alterations in oncogene-driven, advanced NSCLC beyond those in the and the .

Update on Practical Management of Early-Stage Non-Small Cell Lung Cancer (NSCLC): A Report from the Ontario Forum.

Therapeutic strategies for early-stage non-small cell lung cancer (NSCLC) are advancing, with immune checkpoint inhibitors (ICIs) and targeted therapies making their way into neoadjuvant and adjuvant settings. With recent advances, there was a need for multidisciplinary lung cancer healthcare providers from across Ontario to convene and review recent data from practical and implementation standpoints. The focus was on the following questions: (1) To what extent do patient (e.

Programmed Cell Death-Ligand 1 Expression and Clinical Outcomes Among Patients with Resected, Early-Stage Non-Small Cell Lung Cancer: A Real-World Study.

Treatment options for non-small cell lung cancer (NSCLC) are evolving, given recent and expected approvals of immune checkpoint inhibitors (ICIs) targeting programmed cell death-(ligand) 1 (PD-1/PD-L1). We retrospectively evaluated outcomes among patients with resected stage IB-IIIA NSCLC tumors expressing PD-L1 using PALEOS (Pan-cAnadian Lung cancEr Observational Study) data (2016-2019). Key outcomes included PD-L1 expression rate and treatment patterns, recurrence, and median overall (mOS) and disease-free survival (mDFS) among PD-L1+ patients.

Managing Select Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitors.

The increased use of immune checkpoint inhibitors (ICIs) across cancer programs has created the need for standardized monitoring and management of immune-related adverse events (irAEs). Delayed recognition without appropriate treatment can have serious and life-threatening consequences. The management of irAEs presents a unique set of challenges that must be addressed at a multidisciplinary level.

Treatment patterns and outcomes in KRAS-positive advanced NSCLC patients previously treated with immune checkpoint inhibitors: A Canada-wide real-world, multi-center, retrospective cohort study.

Objectives: KRAS mutations, particularly KRAS, are prevalent in non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs) have been a frontline treatment, but recently developed KRAS-selective inhibitors, such as sotorasib, present new therapeutic options. We conducted a multi-center retrospective cohort study to gain insights into real-world treatment patterns and outcomes in patients with KRAS-positive advanced NSCLC receiving systemic therapy post-ICI treatment.

Point of Care Liquid Biopsy for Cancer Treatment-Early Experience from a Community Center.

Liquid biopsy is rapidly becoming an indispensable tool in the oncologist's arsenal; however, this technique remains elusive in a publicly funded healthcare system, and real-world evidence is needed to demonstrate utility and feasibility. Here, we describe the first experience of an in-house point of care liquid biopsy program at a Canadian community hospital. A retrospective review of consecutive cases that underwent plasma-based next-generation sequencing (NGS) was conducted.

Modern era systemic therapies: Expanding concepts of cure in early and locally advanced non-small cell lung cancer.

Cure of cancer is a sensitive and multidimensional concept that is challenging to define, difficult to assert at the individual patient level, and often surrounded by controversy. The notion of cure in non-small cell lung cancer (NSCLC) has changed and continues to evolve with improvements in diagnosis and treatment. Targeted and immune therapies have recently entered the treatment landscape of stage I-III NSCLC.

Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial.

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance-which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment-and developing effective therapies to overcome them, remains an unmet need.

The Perceived Value of Liquid Biopsy: Results From a Canadian Validation Study of Circulating Tumor DNA Testing-Patient's Willingness-to-Pay: A Brief Report.

Introduction: Liquid biopsy is recommended to diagnose molecular resistance to targeted therapy in patients with lung cancer. Nevertheless, not all jurisdictions provide funding and patient access. We report patients' perceived value of liquid biopsy in targeted therapy resistance.

Patient-Reported Health-Related Quality of Life in KEYNOTE-604: Pembrolizumab or Placebo Added to Etoposide and Platinum as First-Line Therapy for Extensive-Stage SCLC.

Introduction: In the phase 3 KEYNOTE-604 study (NCT03066778), pembrolizumab plus etoposide and platinum chemotherapy (EP) significantly ( = 0.0023) improved progression-free survival versus placebo plus EP in previously untreated extensive-stage SCLC (ES-SCLC). We present health-related quality of life (HRQoL) results from KEYNOTE-604.

Programmed Cell Death Protein 1 Inhibitors and MET Targeted Therapies in NSCLC With Exon 14 Skipping Mutations: Efficacy and Toxicity as Sequential Therapies.

Introduction: NSCLC with exon 14 skipping mutation (ex14) is associated with poor outcomes. Integration of novel targeted therapies is challenging because of barriers in testing and drug access. We, therefore, sought to characterize the treatment patterns, outcomes, and emerging issues of treatment sequencing in patients with ex14-mutant NSCLC.

Canadian Consensus Recommendations on the Management of KRAS G12C-Mutated NSCLC.

Activating mutations in , in particular, a point mutation leading to a glycine-to-cysteine substitution at codon 12 (G12C), are among the most frequent genomic alterations in non-small cell lung cancer (NSCLC). Several agents targeting KRAS G12C have recently entered clinical development. Sotorasib, a first-in-class specific small molecule that irreversibly inhibits KRAS G12C, has since obtained Health Canada approval.

Canadian Consensus Recommendations on the Management of Extensive-Stage Small-Cell Lung Cancer.

Small-cell lung cancer (SCLC) is an aggressive, neuroendocrine tumour with high relapse rates, and significant morbidity and mortality. Apart from advances in radiation therapy, progress in the systemic treatment of SCLC had been stagnant for over three decades despite multiple attempts to develop alternative therapeutic options that could improve responses and survival. Recent promising developments in first-line and subsequent therapeutic approaches prompted a Canadian Expert Panel to convene to review evidence, discuss practice patterns, and reach a consensus on the treatment of extensive-stage SCLC (ES-SCLC).

Comparison of tumor-agnostic and tumor-specific clinical oncology trial designs: a systematic review and meta-analysis.

To examine whether tumor-specific and tumor-agnostic oncology trials produce comparable estimates of objective response rate (ORR) in -altered cancers. Electronic database searches were performed to identify phase I-III clinical trials testing tyrosine kinase inhibitors from 2000 to 2021. A random-effects model was used to pool ORRs.

Feasibility of Point-of-Care Genomic Profiling in the Diagnosis and Treatment of Cancer of Unknown Primary.

Introduction: Cancer of unknown primary remains a challenging clinical entity. Despite receiving empiric chemotherapy, median overall survival is approximately 6-12 months. Site-specific therapy based on molecular characterization has been shown to improve outcomes; however, feasibility outside of clinical trials, especially in community centers, is lacking.

Cost Savings of Expedited Care with Upfront Next-Generation Sequencing Testing versus Single-Gene Testing among Patients with Metastatic Non-Small Cell Lung Cancer Based on Current Canadian Practices.

This study assessed the total costs of testing, including the estimated costs of delaying care, associated with next-generation sequencing (NGS) versus single-gene testing strategies among patients with newly diagnosed metastatic non-small cell lung cancer (mNSCLC) from a Canadian public payer perspective. A decision tree model considered testing for genomic alterations using tissue biopsy NGS or single-gene strategies following Canadian guideline recommendations. Inputs included prevalence of mNSCLC, the proportion that tested positive for each genomic alteration, rebiopsy rates, time to test results, testing/medical costs, and costs of delaying care based on literature, public data, and expert opinion.

Evaluation of Cost-Effectiveness of Adjuvant Osimertinib in Patients with Resected EGFR Mutation-Positive Non-small Cell Lung Cancer.

Background: For many patients with resected epidermal growth factor receptor mutation-positive (EGFRm) non-small cell lung cancer (NSCLC), current standard of care (SoC) is adjuvant chemotherapy; however, disease recurrence remains high. Based on positive results from ADAURA (NCT02511106), adjuvant osimertinib was approved for treatment of resected stage IB‒IIIA EGFRm NSCLC.

Objective: The aim was to assess the cost-effectiveness of adjuvant osimertinib in patients with resected EGFRm NSCLC.

Atezolizumab versus chemotherapy in advanced or metastatic NSCLC with high blood-based tumor mutational burden: primary analysis of BFAST cohort C randomized phase 3 trial.

Tumor mutational burden (TMB) is being explored as a predictive biomarker for cancer immunotherapy outcomes in non-small cell lung cancer. BFAST (NCT03178552)-an open-label, global, multicohort trial-evaluated the safety and efficacy of first-line targeted therapies or immunotherapy in patients with unresectable Stage IIIB or IV advanced or metastatic non-small cell lung cancer who were selected for biomarker status using blood-based targeted next-generation sequencing. In the Phase 3 cohort C evaluating blood-based (b)TMB as a biomarker of atezolizumab efficacy, patients with bTMB of ≥10 (N = 471) were randomized 1:1 to receive atezolizumab or platinum-based chemotherapy per local standard of care.