A phase 1b study of cofetuzumab pelidotin monotherapy in patients with PTK7-expressing recurrent non-small cell lung cancer.

Background: Protein tyrosine kinase 7 (PTK7) overexpression in lung cancer is associated with tumor progression. Cofetuzumab pelidotin (Cofe-P) is an antibody-drug conjugate comprising an anti-PTK7 antibody conjugated to a microtubule inhibitor. Herein, we report the results of a phase 1b study evaluating Cofe-P safety, efficacy, and pharmacokinetics in patients with recurrent non-small cell lung cancer (NSCLC).

Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein-Overexpressing Advanced Nonsquamous -Wildtype Non-Small Cell Lung Cancer in the Phase II LUMINOSITY Trial.

Purpose: Telisotuzumab vedotin (Teliso-V) is a c-Met-directed antibody-drug conjugate with a monomethyl auristatin E cytotoxic payload. The phase II LUMINOSITY trial (ClinicalTrials.gov identifier: NCT03539536) aimed to identify the optimal c-Met protein-overexpressing non-small cell lung cancer (NSCLC) population for treatment with Teliso-V (stage I) and expand the selected group for efficacy evaluation (stage II).

Converging survival trends in non-small cell lung cancer patients with and without brain metastasis receiving state-of-the-art treatment.

Introduction: Historically, patients with brain metastasis (BM) have been excluded from clinical trials investigating treatments for non-small cell lung cancer (NSCLC) due to their unfavorable prognosis. Advanced treatments have increased survival prospects for NSCLC patients with BM. This study evaluated the life expectancy of NSCLC patients with and without BM in the context of contemporary treatments.

Blood-Derived Exosomal hTERT mRNA in Patients with Lung Cancer: Characterization and Correlation with Response to Therapy.

Telomerase (human telomerase reverse transcriptase (hTERT) is considered a hallmark of cancer, being active in cancer cells but repressed in human somatic cells. As such, it has the potential to serve as a valid cancer biomarker. Exosomal hTERT mRNA can be detected in the serum of patients with solid malignancies but not in healthy individuals.

mutations detected by tumour next-generation sequencing in non-small cell lung cancer: impact on response to therapy and disease course.

Background: Data regarding the prevalence and clinical relevance of mutations in non-small cell lung cancer (NSCLC) is limited. Our objective was to evaluate the impact of pathogenic variants detected by tumour next-generation sequencing (NGS) on disease course and response to therapy.

Methods: We performed a retrospective analysis of all consecutive NSCLC patients with available NGS reports in a single institution between 01/2015 and 08/2020.

Correlations between pathogenic variants in DNA repair genes and anticancer treatment efficacy in stage IV non-small cell lung cancer: A large real-world cohort and review of the literature.

Background: Mutations in genes involved in DNA damage repair (DDR), a hallmark of cancer, are associated with increased cancer cell sensitivity to certain therapies. This study sought to evaluate the association of DDR pathogenic variants with treatment efficacy in patients with advanced non-small cell lung cancer (NSCLC).

Methods: A retrospective cohort of consecutive patients with advanced NSCLC attending a tertiary medical center who underwent next-generation sequencing in 01/2015-8/2020 were clustered according to DDR gene status and compared for overall response rate (ORR), progression-free survival (PFS) (patients receiving systemic therapy), local PFS (patients receiving definitive radiotherapy), and overall survival (OS) using log-rank and Cox regression analyses.

Arterial and Venous Thromboembolism in ALK-Rearrangement-Positive Non-small Cell Lung Cancer: A Population-Based Cohort Study.

Introduction: There is scarce data regarding the incidence of venous thromboembolism (VTE) and arterial thromboembolism (ATE) in the molecular subtypes of non-small cell lung cancer (NSCLC). We aimed to investigate the association between Anaplastic Lymphoma Kinase (ALK)-positive NSCLC and thromboembolic events.

Methods: A retrospective population-based cohort study of the Clalit Health Services database, included patients with NSCLC diagnosed between 2012 and 2019.

Driver mutation characteristics of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in advanced non-small cell lung cancer.

Objectives: The identification and targeting of actionable genomic alterations (AGA) have revolutionized the treatment of cancer in general and mostly for non-small cell lung cancer (NSCLC). We investigated whether in NSCLC patients PIK3CA mutations are actionable.

Materials And Methods: Chart review was performed of advanced NSCLC patients.

Multinational Analysis of Estimated Health Care Costs Related to Extended-Interval Fixed Dosing of Checkpoint Inhibitors.

Importance: New dosing options for immune checkpoint inhibitors have recently been approved by the US Food and Drug Administration (FDA), including fixed dosing with extended intervals. Although the dose intensity appears the same, there is expected to be some waste with extended-interval dosing, as some drug remains in the bloodstream once a decision to stop treatment is made. The economic impact of extended-interval fixed dosing is unknown compared with standard-interval fixed dosing.

UNcommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-Life Practice in First-LiNe Setting (UNICORN).

Introduction: Approximately 10% of EGFR mutations (EGFRmuts) are uncommon (ucEGFRmuts). We aimed to collect real-world data about osimertinib for patients with ucEGFRmuts.

Methods: This is a multicenter, retrospective study of ucEGFRmut (exon 20 insertions excluded) metastatic NSCLC treated with osimertinib as first EGFR inhibitor.

Selective Intra-Arterial Doxorubicin Eluting Microsphere Embolization for Desmoid Fibromatosis: A Combined Prospective and Retrospective Study.

Desmoid fibromatoses (DFs) are locally aggressive tumors composed of monoclonal fibroblasts within an abundant extracellular matrix. Systemic doxorubicin treatment is effective, but toxic. We investigated arterial doxorubicin eluting embolization (DEE), an approach characterized by high drug concentrations in the tumor alongside limited systemic drug exposure.

NEPTUNE: Phase 3 Study of First-Line Durvalumab Plus Tremelimumab in Patients With Metastatic NSCLC.

Introduction: NEPTUNE, a phase 3, open-label study, evaluated first-line durvalumab plus tremelimumab versus chemotherapy in metastatic NSCLC (mNSCLC).

Methods: Eligible patients with EGFR and ALK wild-type mNSCLC were randomized (1:1) to first-line durvalumab (20 mg/kg every 4 weeks until progression) plus tremelimumab (1 mg/kg every 4 weeks for up to four doses) or standard chemotherapy. Randomization was stratified by tumor programmed death-ligand 1 expression (≥25% versus <25%), tumor histologic type, and smoking history.

Real-world experience with capmatinib in exon 14-mutated non-small cell lung cancer (RECAP): a retrospective analysis from an early access program.

Background: Patients with non-small cell lung cancer (NSCLC) presenting with mesenchymal-epithelial transition () exon 14 skipping mutation have an unfavorable prognosis with standard treatments. Capmatinib is a selective MET inhibitor, which showed promising efficacy in this patient population in early trials.

Methods: We performed a retrospective, international, multicenter efficacy and safety analysis in patients with NSCLC treated with capmatinib in an early access program between March 2019 and December 2021.

Longitudinal plasma proteomic profiling of patients with non-small cell lung cancer undergoing immune checkpoint blockade.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the cancer therapy landscape due to long-term benefits in patients with advanced metastatic disease. However, robust predictive biomarkers for response are still lacking and treatment resistance is not fully understood.

Methods: We profiled approximately 800 pre-treatment and on-treatment plasma proteins from 143 ICI-treated patients with non-small cell lung cancer (NSCLC) using ELISA-based arrays.

The Impact of Comprehensive Genomic Profiling (CGP) on the Decision-Making Process in the Treatment of ALK-Rearranged Advanced Non-Small Cell Lung Cancer (aNSCLC) After Failure of 2/3-Generation ALK Tyrosine Kinase Inhibitors (TKIs).

Background: The use of CGP in guiding treatment decisions in aNSCLC with acquired resistance to ALK TKIs is questionable.

Methods: We prospectively assessed the impact of CGP on the decision-making process in ALK-rearranged aNSCLC patients following progression on 2/3-generation ALK TKIs. Physician's choice of the most recommended next-line systemic treatment (NLST) was captured before and after receival of CGP results; the percentage of cases in which the NLST recommendation has changed was assessed along with the CGP turnaround time (TAT).

Development of Pericardial Effusion in Non-small Cell Lung Cancer Is Associated with the Presence of EGFR/ALK Mutations.

Background: No specific clinical or histological factors are recognized to be associated with the development of pericardial effusion in non-small cell lung cancer (NSCLC) other than a metastatic disease.

Objectives: To assess whether specific clinical and histological features are associated with development of pericardial effusion in patients with NSCLC.

Methods: A consecutive cohort of patients with NSCLC who presented with symptomatic pericardial effusion 2014-2017 was compared to a control group of patients with advanced NSCLC without pericardial effusion.

ALK Inhibitors or Chemotherapy for Third Line in ALK-positive NSCLC? Real-world Data.

Objectives: ALK inhibitors (ALKi) are the standard-of-care treatment for metastatic ALK-rearranged non-small cell lung cancer (NSCLC) in the first- and second-line setting. We conducted a real-world multi-institutional analysis, aiming to compare the efficacy of third-line ALKi versus chemotherapy in these patients.

Methods: Consecutive ALK-positive metastatic NSCLC patients treated with at least one ALKi were identified in the working databases of 7 Israeli oncology centers (the full cohort).

Osimertinib in advanced EGFR-mutant lung adenocarcinoma with asymptomatic brain metastases: an open-label, 3-arm, phase II pilot study.

Background: Osimertinib is selective for both epidermal growth factor receptor (EGFR)-tyrosine-kinase inhibitor (TKI) sensitizing and Thr790Met mutations. While intracranial activity of osimertinib is documented in larger trials, a prospective study focusing exclusively on patients with asymptomatic brain metastases has not been reported.

Methods: In this nonrandomized, phase II, open-label, 3-arm prospective proof-of-concept pilot study, 48 patients with metastatic EGFR-mutant lung adenocarcinoma (LUAD) received osimertinib 80 mg daily.

Durvalumab after concurrent chemotherapy and high-dose radiotherapy for locally advanced non-small cell lung cancer.

The standard of care for stage III non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by durvalumab. Although doses higher than 66 Gy are standard in our center, they were used in only 6.9% of patients in the PACIFIC trial.

Abdominal Desmoid: Course, Severe Outcomes, and Unique Genetic Background in a Large Local Series.

Introduction: Abdominal desmoid tumors are locally aggressive tumors that develop in familial adenomatous polyposis (FAP) patients, within the mesentery or abdominal wall. The understanding and implications of the treatment regimens are evolving.

Aim: To assess the course, treatment, and outcomes of FAP and non-FAP abdominal desmoids and their related genetic alterations.

The Relationship of Diabetes Mellitus to Efficacy of Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer.

Introduction: Immune checkpoint inhibitors (ICI) are the new standard therapy in patients with metastatic NSCLC (mNSCLC). Metformin, previously associated with improved chemotherapy efficacy in diabetic and nondiabetic cancer patients, was recently associated with increased ICI efficacy. In this study, we aimed to explore the correlations between diabetes mellitus (DM), metformin use, and benefit from ICI in mNSCLC patients.

Evaluation of Seropositivity Following BNT162b2 Messenger RNA Vaccination for SARS-CoV-2 in Patients Undergoing Treatment for Cancer.

Importance: Patients with cancer undergoing treatment are at high risk of COVID-19 following SARS-CoV-2 infection; however, their ability to produce an adequate antibody response to messenger RNA SARS-CoV-2 vaccines is unclear.

Objective: To evaluate rates of antispike (anti-S) antibody response to a BNT162b2 vaccine in patients with cancer who are undergoing systemic treatment vs healthy controls.

Design, Setting, And Participants: This prospective cohort study included 102 adult patients with solid tumors undergoing active intravenous anticancer treatment and 78 controls who received the second dose of the BNT162b2 vaccine at least 12 days before enrollment.

BAP1-Altered Malignant Pleural Mesothelioma: Outcomes With Chemotherapy, Immune Check-Point Inhibitors and Poly(ADP-Ribose) Polymerase Inhibitors.

Objectives: Little is known regarding the outcomes of systemic treatments in BAP1-altered malignant pleural mesothelioma (MPM).

Materials And Methods: Forty five patients with MPM [group A: eight MPM patients with BAP1 inactivating mutation/copy number loss (FoundationOne CDx/TEMPUSxT), selected from the electronic databases of four Israeli cancer centers (ICC); group B: 37 consecutive (years 2016-2018) MPM patients selected from the electronic databases of two ICC-of those six patients without a BAP1 alteration (group B1) and 31 patients not tested for BAP1 (group B2)] were analyzed for ORR, PFS (mRECIST), and OS with 1-line platinum/pemetrexed+/-antiangiogenic drug (CT, n-28), immune check-point inhibitors (ICPi, n-16) and poly (ADP-ribose) polymerase inhibitors (PARPi, n-4). OS since diagnosis (OSDx) was assessed.

Venous thromboembolism incidence and risk assessment in lung cancer patients treated with immune checkpoint inhibitors.

Background: There are scarce data on venous thromboembolism (VTE) rates among non-small cell lung cancer (NSCLC) patients treated with immune-checkpoint inhibitors (ICI). The Khorana Score (KS), used to guide thromboprophylaxis in cancer patients, was validated in patients receiving chemotherapy.

Objective: To assess VTE rates and KS performance among NSCLC patients treated with ICI or chemotherapy.

Real-world survival outcomes with immune checkpoint inhibitors in large-cell neuroendocrine tumors of lung.

Background: Little is known regarding the efficacy of immune checkpoint inhibitors (ICI) in patients with advanced large-cell neuroendocrine lung carcinoma (aLCNEC).

Methods: 125 consecutive patients with aLCNEC were identified in the electronic databases of 4 participating cancer centers. The patients were divided into group A (patients who received ICI, n=41) and group B (patients who did not receive ICI, n=84).