Amivantamab Plus Lazertinib in Patients With EGFR-mutant Non-small Cell Lung Cancer (NSCLC) After Progression on Osimertinib and Platinum-based Chemotherapy: Results From CHRYSALIS-2 Cohort A.

Introduction: Treatment options for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with disease progression on/after osimertinib and platinum-based chemotherapy are limited.

Methods: CHRYSALIS-2 Cohort A evaluated amivantamab+lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on/after osimertinib and platinum-based chemotherapy. Primary endpoint was investigator-assessed objective response rate (ORR).

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.

Association of Lung Immune Prognostic Index (LIPI) with Disease Control Rate and Progression-Free Survival in Patients with Soft-Tissue Sarcoma Treated with Immunotherapy in Early-Phase Trials.

Background: The efficacy of immunotherapies in soft-tissue sarcomas (STSs) is limited, and biomarkers of response are lacking. The lung immune prognostic index (LIPI) is a prognostic biomarker used with immunotherapy across cancer types. This study investigates the association of LIPI with the disease control rate (DCR) and progression-free survival (PFS) in patients with STS treated with immunotherapy versus other therapies in early-phase trials.

Antecedent viral immunization and efficacy of immune checkpoint blockade: an extensive serum antibody profile to predict outcomes in non-small cell lung cancer.

Introduction: Immune checkpoint blockers (ICBs) revolutionized the treatment of patients with advanced non-small cell lung cancer (NSCLC) but only a fraction of them obtain a response, and clinical benefit from these treatments is often difficult to predict. The aim of our study is to unveil the potential implications of antibody response to previous viral infections in predicting response to ICBs in patients with NSCLC.

Methods: Sera from patients treated with ICBs alone, chemotherapy (CT) or a combination of CT-ICBs were analyzed with VirScan (CDI Labs, USA), a high-throughput method that comprehensively analyzes epitope-level antiviral IgG antibodies via programmable phage display and immunoprecipitation sequencing.

Validation of the Lung Immune Prognostic Index in patients with untreated advanced non-small cell lung cancer: Post hoc analysis of the IMpower 130, 131 and 150 trials.

Introduction: LIPI has been strongly correlated with immunotherapy (IT) outcomes in advanced NSCLC. Limited data is available for upfront chemotherapy (CT) + IT combinations. We aimed to study its prognostic value in 1st-line CT +/- IT +/- antiangiogenics.

Liquid Biopsy versus CT: Comparison of Tumor Burden Quantification in 1065 Patients with Metastases.

Background Tumor fraction (TF) at liquid biopsy is a potential noninvasive marker for tumor burden, but validation is needed. Purpose To evaluate TF as a potential surrogate for tumor burden, assessed at contrast-enhanced CT across diverse metastatic cancers. Methods This retrospective monocentric study included patients with cancer and metastatic disease, with TF results and contemporaneous contrast-enhanced CT performed between January 2021 and January 2023.

Neoadjuvant immunotherapy strategies for resectable non-small cell lung cancer (NSCLC): Current evidence among special populations and future perspectives.

About one third of patients with Non-Small Cell Lung Cancer (NSCLC) presents at diagnosis with localized or locally advanced disease amenable to curative surgical resection. Surgical operability refers to stage I to IIIA and selected stage IIIB NSCLC. One of the main challenges in the management of early-stage resectable NSCLC is the optimization of available therapeutic strategies to prevent local and distant disease relapse, thus improving survival outcomes.

DNA methylation as a new tool for the differential diagnosis between T-LBL and lymphocyte-rich thymoma.

T-lymphoblastic lymphoma (T-LBL) and thymoma are two rare primary tumors of the thymus deriving either from T-cell precursors or from thymic epithelial cells, respectively. Some thymoma subtypes (AB, B1, and B2) display numerous reactive terminal deoxynucleotidyl transferase-positive (TdT) T-cell precursors masking epithelial tumor cells. Therefore, the differential diagnosis between T-LBL and TdT T-lymphocyte-rich thymoma could be challenging, especially in the case of needle biopsy.

Ocular adverse events associated with antibody-drug conjugates used in cancer: Focus on pathophysiology and management strategies.

Antibody-drug conjugates (ADCs) are designed to maximize cancer cell death with lower cytotoxicity toward noncancerous cells and are an increasingly valuable option for targeted cancer therapies. However, anticancer treatment with ADCs may be associated with ocular adverse events (AEs) such as dry eye, conjunctivitis, photophobia, blurred vision, and corneal abnormalities. While the pathophysiology of ADC-related ocular AEs has not been fully elucidated, most ocular AEs are attributed to off-target effects.

Understanding and Overcoming Resistance to Selective FGFR Inhibitors across FGFR2-Driven Malignancies.

Purpose: Understanding resistance to selective FGFR inhibitors is crucial to improve the clinical outcomes of patients with FGFR2-driven malignancies.

Experimental Design: We analyzed sequential ctDNA, ± whole-exome sequencing, or targeted next-generation sequencing on tissue biopsies from patients with tumors harboring activating FGFR2 alterations progressing on pan-FGFR-selective inhibitors, collected in the prospective UNLOCK program. FGFR2::BICC1 Ba/F3 and patient-derived xenograft models were used for functional studies.

Assessing actionability and incidental findings of germline variants in two precision oncology trials.

Introduction: High-throughput sequencing techniques have revolutionized oncology. Paired germline-tumor DNA analysis has emerged as a comprehensive strategy to uncover actionable alterations in advanced cancer patients (ACP) enrolled in precision oncology trials. However, challenges persist in variant interpretation and managing incidental germline findings.

Clinical and molecular features of early onset pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PDAC) is a major health burden and may become the second cause of death by cancer in developed countries. The incidence of early-onset pancreatic cancer (EOPC, defined by an age at diagnosis <50 years old) is increasing. Here, we conducted a study of all PDAC patients followed at our institution.

Disease Course and Treatment Outcomes in Patients With De Novo Small-Cell Lung Cancer and Epidermal Growth Factor Receptor Exon 20 Insertion: Two Case Reports.

We report the first two cases of EGFR exon20ins SCLC, treated with amivantamab and TKIs.

Impact of pembrolizumab treatment duration on overall survival and prognostic factors in advanced non-small cell lung cancer: a nationwide retrospective cohort study.

Background: The efficacy of front-line pembrolizumab has been established in studies that limit treatment duration to 2 years, but decision to stop pembrolizumab after 2 years is often at physician's discretion. ATHENA is a retrospective cohort study using a comprehensive administrative database aimed firstly at exploring the optimal duration of pembrolizumab and secondly real-life prognosis factors in patients with advanced non-small cell lung cancer (NSCLC).

Methods: Using the French National Health Insurance database (SNDS), we identified patients with incident lung cancer in France from 2015 to 2022.

Outcomes of right sleeve lower lobectomy vs. lower bilobectomy for lung malignancies.

Objectives: Lower bilobectomy (LBL) leaves a residual pleural space potentially associated with adverse postoperative outcomes. In selected patients, right sleeve lower lobectomy (RSLL) with anastomosis between the middle lobe bronchus and intermediate bronchus is feasible. The outcomes of RSLL and LBL have not been compared.

Circulating tumor DNA to guide diagnosis and treatment of localized and locally advanced non-small cell lung cancer.

Liquid biopsy is a minimally invasive method for biomarkers detection in body fluids, particularly in blood, which offers an elevated and growing number of clinical applications in oncology. As a result of the improvement in the techniques for DNA analysis, above all next-generation sequencing (NGS) assays, circulating tumor DNA (ctDNA) has become the most informing tumor-derived material for most types of cancer, including non-small cell lung cancer (NSCLC). Although ctDNA concentration is higher in patients with advanced tumors, it can be detected even in patients with early-stage disease.

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.