Polyradiculitis as a Neurological Complication Associated with Adagrasib: A Case Report.

Introduction: Adagrasib is an upcoming anticancer treatment for KRAS G12C-mutated non-small-cell lung carcinoma, colorectal cancer and potentially other solid tumors harboring this mutation. It is generally well-tolerated and reports of neurological adverse events so far have been limited.

Case Presentation: We present to our best knowledge the first case of a 70-year-old woman who was admitted with polyradiculitis as a treatment-related complication of adagrasib.

Safety, Efficacy, and Biomarker Analysis of Crizotinib in MET-Mutated Non-Small Cell Lung Cancer-Results from the Drug Rediscovery Protocol.

Purpose: To provide patients with MET-mutated advanced non-small cell lung cancer (METmut aNSCLC) access to crizotinib, further substantiate evidence of its efficacy and safety in this setting, and find potential biomarkers for nonresponse.

Patients And Methods: In the Drug Rediscovery Protocol (NCT0295234), patients with an actionable molecular profile are treated with off-label registered drugs. Both treated and untreated patients with aNSCLC harboring MET exon 14 skipping or other MET mutations received crizotinib 250 mg BID until disease progression or intolerable toxicity.

Cost-effectiveness analysis of a lung cancer screening program in the netherlands: a simulation based on NELSON and NLST study outcomes.

Background: In the Netherlands, lung cancer is the leading cause of cancer-related death, accounting for more than 10,000 annual deaths. Lung cancer screening (LCS) studies using low-dose computed tomography (LDCT) have demonstrated that early detection reduces lung cancer mortality. However, no LCS program has been implemented yet in the Netherlands.

Development and validation of an ultra-performance liquid chromatography-tandem mass spectrometry method to quantify the small molecule inhibitors adagrasib, alectinib, brigatinib, capmatinib, crizotinib, lorlatinib, selpercatinib, and sotorasib in human plasma.

Small molecule inhibitors (SMIs) are increasingly being used in the treatment of non-small cell lung cancer. To support pharmacokinetic research and clinical treatment monitoring, our aim was to develop and validate an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) assay for quantification of eight SMIs: adagrasib, alectinib, brigatinib, capmatinib, crizotinib, lorlatinib, selpercatinib, and sotorasib. Development of the UPLC-MS/MS assay was done by trying different columns and eluents to optimize peak shape.

Head-to-head comparison of composite and individual biomarkers to predict clinical benefit to PD-1 blockade in non-small cell lung cancer.

Background: The efficacy of PD-1 blocking agents in advanced NSCLC has shown prolonged effectiveness, but only in a minority of patients. Multiple biomarkers have been explored to predict treatment benefit, yet their combined performance remains inadequately examined. In this study, we assessed the combined predictive performance of multiple biomarkers in NSCLC patients treated with nivolumab.

Model-Informed Development of a Cost-Saving Dosing Regimen for Sacituzumab Govitecan.

Background: The antibody-drug conjugate sacituzumab govitecan is approved for metastatic triple-negative breast cancer and has shown promising results in various other types of cancer. Its costs may limit patient access to this novel effective treatment modality.

Objective: The purpose of this study was to develop an evidence-based rational dosing regimen that results in targeted drug exposure within the therapeutic range while minimizing financial toxicity, to improve treatment access.

Proactive monitoring of drug-drug interactions between direct oral anticoagulants and small-molecule inhibitors in patients with non-small cell lung cancer.

Background: Small-molecule inhibitors (SMIs) have revolutionised the treatment of non-small cell lung cancer (NSCLC). However, SMI-induced drug-drug interactions (DDIs) with frequently co-administered direct oral anticoagulants (DOACs), increase thromboembolic and bleeding risks. This study investigated and proactively managed the consequences of DOAC-SMI DDIs.

Cerebrospinal Fluid Concentration of the RET Inhibitor Pralsetinib: A Case Report.

Introduction: Pralsetinib is used to treat metastatic RET fusion-positive non-small cell lung cancer. Preclinical studies of pralsetinib have shown blood-brain barrier (BBB) penetration and intracranial activity. The intracranial efficacy of pralsetinib in patients with brain metastasis is considered to be greater compared to older multikinase tyrosine kinase inhibitors.

Integrating treatment cost reduction strategies and biomarker research to reduce costs and personalize expensive treatments: an example of a self-funding trial in non-small cell lung cancer.

Personalization of treatment offers the opportunity to treat patients more effectively based on their dominant disease-specific features. The increasing number and types of treatment, and the high costs associated with these treatments, however, demand new approaches that improve patient selection while reducing treatment-associated costs to ensure sustainable healthcare. The DEDICATION-1 trial has been designed to investigate the non-inferiority of lower dosing regimens when compared to standard of care dosing regimens as a potential effective treatment cost reduction strategy to reduce costs of treatment with expensive immune checkpoint inhibitors in non-small cell lung cancer.

A Dysfunctional T-cell Gene Signature for Predicting Nonresponse to PD-1 Blockade in Non-small Cell Lung Cancer That Is Suitable for Routine Clinical Diagnostics.

Purpose: Because PD-1 blockade is only effective in a minority of patients with advanced-stage non-small cell lung cancer (NSCLC), biomarkers are needed to guide treatment decisions. Tumor infiltration by PD-1T tumor-infiltrating lymphocytes (TIL), a dysfunctional TIL pool with tumor-reactive capacity, can be detected by digital quantitative IHC and has been established as a novel predictive biomarker in NSCLC. To facilitate translation of this biomarker to the clinic, we aimed to develop a robust RNA signature reflecting a tumor's PD-1T TIL status.

Impact of time-to-treatment on survival for early-stage non-small cell lung cancer in The Netherlands-a nationwide observational cohort study.

Background: Varied outcomes on the relation between time-to-treatment and survival in early-stage non-small cell lung cancer (NSCLC) patients are reported. We examined this relation in a large multicentric retrospective cohort study and identified factors associated with extended time-to-treatment.

Methods: We included 9,536 patients with clinical stage I-II NSCLC, diagnosed and treated in 2014-2019, from the Netherlands Cancer Registry that includes nation-wide data.

Prognostic Value of Nivolumab Clearance in Non-Small Cell Lung Cancer Patients for Survival Early in Treatment.

Introduction: Immune checkpoint inhibitors improved survival of advanced stage non-small cell lung cancer patients, but the overall response rate remains low. A biomarker that identifies non-responders would be helpful to allow treatment decisions. Clearance of immune checkpoint inhibitors is related to treatment response, but its prognostic potential early in treatment remains unknown.

Detection of dendritic cell subsets in the tumor microenvironment by multiplex immunohistochemistry.

Dendritic cells (DCs) are essential in antitumor immunity. In humans, three main DC subsets are defined: two types of conventional DCs (cDC1s and cDC2s) and plasmacytoid DCs (pDCs). To study DC subsets in the tumor microenvironment (TME), it is important to correctly identify them in tumor tissues.

Comparing modeling strategies combining changes in multiple serum tumor biomarkers for early prediction of immunotherapy non-response in non-small cell lung cancer.

Background: Patients treated with immune checkpoint inhibitors (ICI) are at risk of adverse events (AEs) even though not all patients will benefit. Serum tumor markers (STMs) are known to reflect tumor activity and might therefore be useful to predict response, guide treatment decisions and thereby prevent AEs.

Objective: This study aims to compare a range of prediction methods to predict non-response using multiple sequentially measured STMs.

Pre-analytical stability of the CEA, CYFRA 21.1, NSE, CA125 and HE4 tumor markers.

Background: For lung cancer, circulating tumor markers (TM) are available to guide clinical treatment decisions. To ensure adequate accuracy, pre-analytical instabilities need to be known and addressed in the pre-analytical laboratory protocols.

Objective: This study investigates the pre-analytical stability of CA125, CEA, CYFRA 21.

Blood platelet RNA profiles do not enable for nivolumab response prediction at baseline in patients with non-small cell lung cancer.

Background: Anti-PD-(L)1 immunotherapy has emerged as a promising treatment approach for non-small cell lung cancer (NSCLC), though the response rates remain low. Pre-treatment response prediction may improve patient allocation for immunotherapy. Blood platelets act as active immune-like cells, thereby constraining T-cell activity, propagating cancer metastasis, and adjusting their spliced mRNA content.

A Systematic Evaluation of Cost-Saving Dosing Regimens for Therapeutic Antibodies and Antibody-Drug Conjugates for the Treatment of Lung Cancer.

Background: Expensive novel anticancer drugs put a serious strain on healthcare budgets, and the associated drug expenses limit access to life-saving treatments worldwide.

Objective: We aimed to develop alternative dosing regimens to reduce drug expenses.

Methods: We developed alternative dosing regimens for the following monoclonal antibodies used for the treatment of lung cancer: amivantamab, atezolizumab, bevacizumab, durvalumab, ipilimumab, nivolumab, pembrolizumab, and ramucirumab; and for the antibody-drug conjugate trastuzumab deruxtecan.

Therapeutic drug monitoring guided dosing versus standard dosing of alectinib in advanced ALK positive non-small cell lung cancer patients: Study protocol for an international, multicenter phase IV randomized controlled trial (ADAPT ALEC).

Background: Alectinib is first-line therapy in patients with stage IV non-small cell lung carcinoma (NSCLC) and an anaplastic lymphoma kinase (ALK) fusion. A shorter median progression-free survival (mPFS) was observed when alectinib minimum plasma concentrations during steady state (C) were below 435 ng/mL. This may suggest that patients should have an alectinib C ≥ 435 ng/mL for a more favorable outcome.

Clinical perspectives on serum tumor marker use in predicting prognosis and treatment response in advanced non-small cell lung cancer.

The optimal positioning and usage of serum tumor markers (STMs) in advanced non-small cell lung cancer (NSCLC) care is still unclear. This review aimed to provide an overview of the potential use and value of STMs in routine advanced NSCLC care for the prediction of prognosis and treatment response. Radiological imaging and clinical symptoms have shown not to capture a patient's entire disease status in daily clinical practice.

Feasibility of an Individualized Dispensing Program for Patients Prescribed Oral Anticancer Drugs to Prevent Waste.

Purpose: Waste of oral anticancer drugs (OACDs) causes financial and environmental burdens. This study evaluates the feasibility of an individualized dispensing program to prevent waste of OACDs.

Methods: Adult patients were dispensed individualized quantities of niraparib, abiraterone, enzalutamide, ruxolitinib, osimertinib, or imatinib as standard care, during the first 6 months of treatment.

Renal function-based versus standard dosing of pemetrexed: a randomized controlled trial.

Purpose: Pemetrexed is a chemotherapeutic drug in the treatment of non-small cell lung cancer and mesothelioma. Optimized dosing of pemetrexed based on renal function instead of body surface area (BSA) is hypothesized to reduce pharmacokinetic variability in systemic exposure and could therefore improve treatment outcomes. The aim of this study is to compare optimized dosing to standard BSA-based dosing.

Modeling strategies to analyse longitudinal biomarker data: An illustration on predicting immunotherapy non-response in non-small cell lung cancer.

Serum tumor markers acquired through a blood draw are known to reflect tumor activity. Their non-invasive nature allows for more frequent testing compared to traditional imaging methods used for response evaluations. Our study aims to compare nine prediction methods to accurately, and with a low false positive rate, predict progressive disease despite treatment (i.

Tumor microenvironment shows an immunological abscopal effect in patients with NSCLC treated with pembrolizumab-radiotherapy combination.

Background: Immunotherapy is currently part of the standard of care for patients with advanced-stage non-small cell lung cancer (NSCLC). However, many patients do not respond to this treatment, therefore combination strategies are being explored to increase clinical benefit. The PEMBRO-RT trial combined the therapeutic programmed cell death 1 (PD-1) antibody pembrolizumab with stereotactic body radiation therapy (SBRT) to increase the overall response rate and study the effects on the tumor microenvironment (TME).

Diagnosing Non-Small Cell Lung Cancer by Exhaled Breath Profiling Using an Electronic Nose: A Multicenter Validation Study.

Background: Despite the potential of exhaled breath analysis of volatile organic compounds to diagnose lung cancer, clinical implementation has not been realized, partly due to the lack of validation studies.

Research Question: This study addressed two questions. First, can we simultaneously train and validate a prediction model to distinguish patients with non-small cell lung cancer from non-lung cancer subjects based on exhaled breath patterns? Second, does addition of clinical variables to exhaled breath data improve the diagnosis of lung cancer?

Study Design And Methods: In this multicenter study, subjects with non-small cell lung cancer and control subjects performed 5 min of tidal breathing through the aeoNose, a handheld electronic nose device.