Transportability of nonlocal real-world evidence and its relevance to health technology assessment: a primer.

Real-world evidence (RWE) from outside Canada or the UK is sometimes included in submissions to health technology assessments by Canada's Drug Agency/L'Agence des médicaments du Canada (CDA-AMC) and National Institute for Health and Care Excellence when local data are lacking, particularly in rare diseases. However, differences in population demographics, healthcare systems and clinical practice patterns between different jurisdictions can pose challenges for contextualizing nonlocal data for health technology assessments. This primer outlines the challenges of using nonlocal RWE for decision-making, presents assumptions necessary for transportability of RWE, and describes quantitative methods to address these challenges.

Brief Report: Post Hoc Validation of Platinum Ineligibility in NSCLC From the Phase III IPSOS Study.

Introduction: The phase III IPSOS study (NCT03191786) demonstrated that atezolizumab was associated with improved survival, stable patient-reported outcomes, and a favorable safety profile versus single-agent chemotherapy in patients with NSCLC ineligible for platinum-based chemotherapy. As no established consensus criteria for platinum ineligibility exist for NSCLC, we performed a post hoc analysis from IPSOS to evaluate clinical outcomes in a selected platinum-ineligible (sPI) population meeting a refined definition.

Methods: Patients with stage IIIB or IV NSCLC who were ineligible for platinum-doublet chemotherapy were randomized (2:1) to receive atezolizumab or single-agent chemotherapy (vinorelbine or gemcitabine).

Mortality Outcomes in People with Lung Cancer with and without Type2 Diabetes: A Cohort Study in England.

Introduction: The impact of type 2 diabetes (T2DM) on mortality following lung cancer diagnosis remains unclear, with conflicting evidence across studies. We aimed to assess differences in all-cause and cause-specific mortality between people with lung cancer with and without T2DM within a primary care population in England.

Methods: The study population was 69,674 people with incident lung cancer within the Clinical Practice Research Datalink (CPRD) Aurum primary care database (2010-2022).

Quantitative Bias Analysis for Single-Arm Trials With External Control Arms.

Importance: Unmeasured confounding is a key concern for decision-makers when observational datasets are used to assemble external control arms (ECAs) for single-arm trials.

Objective: To investigate the utility of quantitative bias analysis (QBA) for exploring the sensitivity to unmeasured confounding of nonrandomized analyses using ECAs.

Design, Setting, And Participants: This study emulated 15 treatment comparisons using experimental arms from existing randomized trials in advanced non-small cell lung cancer (aNSCLC) conducted after 2011 and ECAs derived from observational data.

Utilizing ctDNA to discover mechanisms of resistance to targeted therapies in patients with metastatic NSCLC: towards more informative trials.

Advances in targeted therapies for patients with non-small-cell lung cancer have substantially improved the outcomes of those with actionable alterations in certain oncogenic driver genes. However, acquired resistance to these targeted therapies remains a major challenge. Understanding the mechanisms underlying acquired resistance will be crucial for the development of strategies that might either overcome this effect or delay the onset.

A phase II trial of mTORC1/2 inhibition in STK11 deficient non small cell lung cancer.

There are no current stratified medicine options for STK11-deficient NSCLC. STK11 loss mediates mTORC activation, GLUT1 up-regulation and increased glycolysis. This metabolic reprogramming might represent a therapeutic vulnerability targetable with mTORC1/2 inhibition.

Efficacy and safety of brigatinib in patients with ALK TKI-naive advanced ALK+ NSCLC: Integrated analysis of the ALTA-1L and J-ALTA trials.

Objectives: Brigatinib approval as a first-line anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) for advanced ALK+ non-small cell lung cancer (NSCLC) is supported by results of a non-Japanese global phase 3 trial (ALTA-1L) and a separate phase 2 trial conducted in Japan (J-ALTA). To evaluate outcomes in a larger global patient population, we conducted an integrated analysis of pooled efficacy and safety data from ALTA-1L and J-ALTA.

Materials And Methods: ALTA-1L (NCT02737501) and J-ALTA (NCT03410108) were open-label, multicenter studies of patients with advanced or metastatic ALK+ NSCLC.

An international and multidisciplinary EORTC survey on resectability of stage III non-small cell lung cancer.

Introduction: The EORTC-Lung Cancer Group initiated a Delphi consensus process to establish a consensual definition of resectable stage III non-small cell lung cancer (NSCLC) for the use in clinical trials, including a systematic review, survey, and review of clinical cases. Here, the survey results are presented, aimed to identify areas of controversy.

Methods: A survey was distributed among the members of six international organizations related to lung cancer.

Incidental finding of leukaemia in circulating tumour DNA- the importance of a molecular tumour board.

As the use of liquid biopsies are increasing across multiple indications in cancer medicine, the detection of incidental findings on circulating tumour DNA is of increasing importance. We report the finding of leukaemia detected in a patient who underwent plasma-based circulating tumour DNA next generation screening as part of a screening liquid biopsy study. A BRAF V600E mutation detected was deemed pathogenic following discussion at a molecular tumour board, and recommendation of further investigations led to the diagnosis of an occult haematological malignancy.

Data set for the reporting of lung cancer: recommendations from the International Collaboration on Cancer Reporting (ICCR).

Lung cancer is the leading cause of cancer related deaths worldwide, although some patients with early-stage disease can be cured with surgical resection. Standardised reporting of all clinically relevant pathological parameters is essential for best patient care and is also important for ongoing data collection and refinement of important pathological features that impact patient prognosis, staging and clinical care. Using the established International Collaboration on Cancer Reporting (ICCR) procedure, a representative international expert panel of nine lung pathologists as well as an oncologist was convened.

Assessing the sensitivity and acceptability of the Royal Marsden Palliative Care Referral "Triggers" Tool for outpatients with cancer.

Purpose: To evaluate the use, acceptability, and experience of a seven-item palliative care referral screening tool in an outpatient oncology setting.

Methods: A two-phase convergent parallel mixed-methods study. Patient participants who met any of the "Royal Marsden Triggers Tool" criteria were compared with those who did not in terms of demographic data, palliative care needs (Integrated Palliative Outcome Scale, IPOS) and quality of life indicators (EORTC-QLQ-C30).

Successful Lorlatinib Rechallenge After Severe Drug-Induced Psychosis in ALK-Positive Metastatic NSCLC: A Case Report.

Neurocognitive adverse events (NAEs) have been reported in up to 60% of patients on lorlatinib, a potent central nervous system-active ALK inhibitor. Manifestations may include psychotic, mood, speech, and cognitive symptoms. Current guidance recommends permanent discontinuation of lorlatinib in cases of grade IV NAEs.

Top 20 NSCLC Clinical and Translational Science Papers That Shaped the 20 Years Since the Discovery of Activating Mutations in NSCLC. An Editor-in-Chief Expert Panel Consensus Survey.

The year 2024 is the 20 anniversary of the discovery of activating epidermal growth factor receptor () mutations in non-small cell lung cancer (NSCLC). Since then, tremendous advances have been made in the treatment of NSCLC based on this discovery. Some of these studies have led to seismic changes in the concept of oncology research and spurred treatment advances beyond NSCLC, leading to a current true era of precision oncology for all solid tumors.

Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial.

Background: Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone.

Methods: MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK.

Discordance in Recommendation Between Next-Generation Sequencing Test Reports and Molecular Tumor Boards in India.

Purpose: Accurate understanding of the genomic and transcriptomic data provided by next-generation sequencing (NGS) is essential for the effective utilization of precision oncology. Molecular tumor boards (MTBs) aim to translate the complex data in NGS reports into effective clinical interventions. Often, MTB treatment recommendations differ from those in the NGS reports.