Clinical insight on the pathway of SLFN11 as emergent biomarker in SCLC.

Schlafen 11 (SLFN11) is a gene encoding for a protein involved in the irreversible arrest of cell replication under DNA-damaging stress. SLFN11 is expressed differently across various cancers. When overexpressed, SLFN11 inhibits tumor replication and growth by early recruitment to stressed replication forks, making tumors more sensitive to a range of anti-cancer treatments, including topoisomerase I-II inhibitors, DNA alkylating agents, platinum salts, anti-metabolites, anti-tumor antibiotics, poly ADP-ribose polymerase (PARP) inhibitors and immunotherapies.

TDM-Based Tailored Dosing of Durvalumab in Lung Cancer Patients: A Comprehensive Population Pharmacokinetic-Pharmacoeconomic Evaluation.

Background: The increasing use of immune checkpoint inhibitors, such as durvalumab, places a significant financial burden on healthcare systems, strains hospital capacities, and contributes to environmental concerns.

Objective: We aimed to develop alternative dosing strategies to optimize durvalumab administration, reduce unnecessary drug use, and ensure sustainable cancer care without sacrificing efficacy.

Methods: Using the population pharmacokinetic model developed by the licensing holder, we designed two alternative dosing strategies for non-small cell lung cancer based on therapeutic drug monitoring.

Outcome and safety of lurbinectedin as compassionate use in extensive stage small cell lung cancer: A multicentric international cohort.

Introduction: Lurbinectedin has recently emerged in the treatment landscape of extensive stage (ES) small cell lung cancer (SCLC). Here we report the outcomes and safety of lurbinectedin within a named patient program in a multicentric, international cohort.

Methods: Clinical data of all patients with ES-SCLC treated with lurbinectedin at the Erasmus Medical Center (EMC, Rotterdam-The Netherlands) and the Veneto Institute of Oncology (IOV, Padua-Italy) were collected.

TEIPP-vaccination in checkpoint-resistant non-small cell lung cancer: a first-in-human phase I/II dose-escalation study.

Functional loss of the intracellular peptide Transporter associated with Antigen Processing (TAP) fosters resistance to T-cell based immunotherapy. We discovered the presentation of an alternative set of shared tumor antigens on such escaped cancers and developed a LRPAP1 synthetic long peptide vaccine (TEIPP24) to stimulate T-cell immunity. In this first-in-human multicenter dose-escalation study with extension cohort, HLA-A*0201-positive patients with non-small cell lung cancer progressive after checkpoint blockade were treated with TEIPP24 (NCT05898763).

Folinic Acid Prophylaxis and Dose Adjustments Enable Safe Treatment with Pemetrexed in Patients with Renal Impairment.

Pemetrexed is a cornerstone in chemo(immunotherapy) of non-small cell lung cancer and mesothelioma; however, it is contraindicated in patients with renal impairment due to severe toxicity concerns. Therefore, a large proportion of patients is withheld from effective chemo(immunotherapy). We performed an intra-patient 3 + 3 dose escalation renal impairment study (eGFR < 45 mL/min).

An Evidence-Based Rationale for Dose De-escalation of Subcutaneous Atezolizumab.

Background: Atezolizumab is a programmed death-ligand 1 (PD-L1) checkpoint inhibitor for the treatment of different forms of cancer. The subcutaneous formulation of atezolizumab has recently received approval. However, treatment with atezolizumab continues to be expensive, and the number of patients needing treatment with this drug continues to increase.

Hepatotoxicity in patients with non-small cell lung cancer treated with sotorasib after prior immunotherapy: a comprehensive clinical and pharmacokinetic analysis.

Background: Sotorasib given after immunotherapy could put patients at increased risk of hepatotoxicity. Therefore, there is a need to gain insight into the potential correlation between anti-PD-(L)1 treatment, anti-PD-(L)1 concentrations, sotorasib concentrations, and the incidence of hepatotoxicity during sotorasib.

Methods: Patients with KRAS-mutated NSCLC treated with sotorasib were prospectively enrolled in our biomarker cohort study (NCT05221372).

SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer.

Purpose: The phase III SKYSCRAPER-02 study determined whether the benefits of atezolizumab plus carboplatin and etoposide (CE) could be enhanced by the addition of tiragolumab in untreated extensive-stage small-cell lung cancer (ES-SCLC). We report final progression-free survival (PFS) and overall survival (OS) analyses.

Methods: Patients received tiragolumab 600 mg/placebo, plus atezolizumab 1,200 mg and CE (four cycles), then maintenance tiragolumab/placebo plus atezolizumab.

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.

Analysis of Serious Weight Gain in Patients Using Alectinib for ALK-Positive Lung Cancer.

Introduction: Alectinib is a standard-of-care treatment for metastatic ALK+ NSCLC. Weight gain is an unexplored side effect reported in approximately 10%. To prevent or intervene alectinib-induced weight gain, more insight in its extent and etiology is needed.

Rare thoracic cancers: a comprehensive overview of diagnosis and management of small cell lung cancer, malignant pleural mesothelioma and thymic epithelial tumours.

Despite the progress in outcomes seen with immunotherapy in various malignancies, including nonsmall cell lung cancer, the benefits are less in small cell lung cancer, malignant pleural mesothelioma and thymic epithelial tumours. New effective treatment options are needed, guided more in-depth insights into the pathophysiology of these rare malignancies. This review comprehensively presents an overview of the clinical presentation, diagnostic tools, staging systems, pathophysiology and treatment options for these rare thoracic cancers.

Alternative dosing strategies for immune checkpoint inhibitors to improve cost-effectiveness: a special focus on nivolumab and pembrolizumab.

Immune checkpoint inhibitors have revolutionised cancer treatment by offering durable responses to many patients with solid and haematological cancers. The high prices and increasing use of immune checkpoint inhibitors put considerable strain on health-care budgets globally. This financial strain could jeopardise patients' access to these anti-cancer therapies.

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.

Lurbinectedin shows clinical activity and immune-modulatory functions in patients with pre-treated small cell lung cancer and malignant pleural mesothelioma.

Purpose: Lurbinectedin is a promising new drug being investigated in pre-treated patients with small cell lung cancer (SCLC) or malignant pleural mesothelioma (MPM). Its clinical activity in the real-world setting has not been investigated yet.

Patients And Methods: Clinical data of patients with SCLC and MPM who were treated with lurbinectedin were prospectively collected.

Efficacy, prognosis and safety analysis of anti-PD-1/PD-L1 inhibitor rechallenge in advanced lung cancer patients: a cohort study.

Background: The rechallenge of immune checkpoint inhibitors (ICI) is now an optional strategy for patients who discontinued ICI due to immune-related adverse events (irAEs) or disease progression. However, little data is available for the prognosis and prognostic factors of patients receiving ICI rechallenge treatment in advanced lung cancer patients. Our study aimed to explore the efficacy, prognosis and safety of patients who received anti-programmed cell death-1/programmed cell death ligand 1 (anti-PD-1/PD-L1) inhibitor rechallenge.

BCKDK alters the metabolism of non-small cell lung cancer.

Background: Metabolic reprogramming is a major feature of many tumors including non-small cell lung cancer (NSCLC). Branched-chain α-keto acid dehydrogenase kinase (BCKDK) plays an important role in diabetes, obesity, and other diseases. However, the function of BCKDK in NSCLC is unclear.

Life-prolonging treatment restrictions and outcomes in patients with cancer and COVID-19: an update from the Dutch Oncology COVID-19 Consortium.

Aim Of The Study: The coronavirus disease 2019 (COVID-19) pandemic significantly impacted cancer care. In this study, clinical patient characteristics related to COVID-19 outcomes and advanced care planning, in terms of non-oncological treatment restrictions (e.g.

Phase II trial of natalizumab for the treatment of anti-Hu associated paraneoplastic neurological syndromes.

Background: Paraneoplastic neurological syndromes with anti-Hu antibodies (Hu-PNS) have a very poor prognosis: more than half of the patients become bedridden and median survival is less than 12 months. Several lines of evidence suggest a pathogenic T cell-mediated immune response. Therefore, we conducted a prospective open-label phase II trial with natalizumab.

Defining oligometastatic non-small cell lung cancer: concept versus biology, a literature review.

Objective: In this review, the concept of (synchronous) oligometastatic disease in patients with non-oncogene-driven non-small cell lung cancer (NSCLC) will be placed in the context of tumor biology and metastatic growth patterns. We will also provide considerations for clinical practice and future perspectives, which will ultimately lead to better patient selection and oligometastatic disease outcome.

Background: The treatment landscape of metastasized NSCLC has moved from "one-size fits all" to a personalized approach.

Immunotherapy in small cell lung cancer: one step at a time: a narrative review.

Chemotherapy with or without radiotherapy has been the standard of care for many years for patients with small cell lung cancer (SCLC). Despite exceptionally high responses (up to 80%) with chemotherapy, the majority of patients relapse rapidly within weeks to months after treatment completion. Therefore, new and better treatment options are necessary.