5-Azacytidine treatment inhibits the development of lung cancer models via epigenetic reprogramming and activation of cellular pathways with anti-tumor activity.

Background And Aims: Non-small cell lung cancer (NSCLC) treatment is challenged by late detection and limited therapeutic options. Aberrant DNA methylation, a common epigenetic alteration in NSCLC, offers new therapeutic avenues. This study aims to evaluate the combined effects of 5-Azacytidine (5-Aza), an epigenetic modifier, and ionizing radiation (IR) on NSCLC, exploring the underlying molecular mechanisms and therapeutic potential.

Next-generation sequencing as a valuable tool for mutational spectrum in advanced-stage NSCLC patients.

Background And Aim: Lung cancer remains one of the most threatening malignancies, ranking as the second most diagnosed cancer, and it continues to be the leading cause of cancer-related deaths worldwide. Challenges persist with late diagnosis and the high mutational burden characteristic of lung cancer.

Methods: Our study focuses on identifying the mutational spectrum of a cohort of advanced-stage non-small cell lung cancer (NSCLC) patients using a minimally invasive method through blood collection.

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).

Exploring Therapeutic Avenues in Lung Cancer: The Epigenetic Perspective.

Lung cancer, primarily non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC), is distinguished by its high prevalence and marked mortality rates. Traditional therapeutic approaches, encompassing chemotherapy, radiation, and targeted therapies, frequently show limited efficacy due to acquired resistance and notable side effects. The objective of this review is to introduce a fresh perspective on the therapeutic strategies for lung cancer, emphasizing interventions targeting the epigenetic alterations often seen in this malignancy.

Bempegaldesleukin Plus Nivolumab in Untreated Advanced Melanoma: The Open-Label, Phase III PIVOT IO 001 Trial Results.

Purpose: Despite marked advances in the treatment of unresectable or metastatic melanoma, the need for novel therapies remains. Bempegaldesleukin (BEMPEG), a pegylated interleukin-2 (IL-2) cytokine prodrug, demonstrated efficacy in the phase II PIVOT-02 trial. PIVOT IO 001 (ClinicalTrials.

MicroRNAs expression profile in chemotherapy-induced cardiotoxicity in NSCLC using a co-culture model.

Clinical application of chemotherapy in lung cancer is constrained by side effects, notably cardiotoxicity, the mechanisms of which remain elusive. This study assessed the potential of specific miRNAs as biomarkers for chemotherapy-induced cardiotoxicity in lung cancer. We employed two lung adenocarcinoma cell lines (Calu6 and H1792) and ventricular normal human cardiac fibroblasts (NHCF-V) in single and co-culture experiments.

Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial.

Background: Lurbinectedin is a synthetic marine-derived anticancer agent that acts as a selective inhibitor of oncogenic transcription. Lurbinectedin monotherapy (3·2 mg/m every 3 weeks) received accelerated approval from the US Food and Drug Administration on the basis of efficacy in patients with small-cell lung cancer (SCLC) who relapsed after first-line platinum-based chemotherapy. The ATLANTIS trial assessed the efficacy and safety of combination lurbinectedin and the anthracycline doxorubicin as second-line treatment for SCLC.

Real-World Testing Practices, Treatment Patterns and Clinical Outcomes in Patients from Central Eastern Europe with EGFR-Mutated Advanced Non-Small Cell Lung Cancer: A Retrospective Chart Review Study (REFLECT).

The targeted therapy with tyrosine kinase inhibitors (TKIs) against the epidermal growth factor receptor mutation (EGFRm) in advanced non-small cell lung cancer (NSCLC) changed the treatment paradigm. REFLECT study (NCT04031898) explored / testing and treatment patterns in EGFRm NSCLC patients receiving first- or second-generation (1G/2G) EGFR TKIs as front-line (1L) in eight countries. Pooled data from Central Eastern Europe (CEE) countries from this study (Bulgaria, Poland, Romania, Slovenia) are presented here.

Health-Related Quality of Life Outcomes With Two Different Starting Doses of Lenvatinib in Combination With Everolimus for Previously Treated Renal Cell Carcinoma.

Background: Preserving health-related quality of life (HRQOL) is an important goal during renal cell carcinoma treatment. We report HRQOL outcomes from a phase II trial (NCT03173560).

Patients And Methods: HRQOL data were collected during a multicenter, randomized, open-label phase II study comparing the safety and efficacy of 2 different starting doses of lenvatinib (18 mg vs.

Assessing the Safety and Efficacy of Two Starting Doses of Lenvatinib Plus Everolimus in Patients with Renal Cell Carcinoma: A Randomized Phase 2 Trial.

Background: Lenvatinib (18 mg) plus everolimus (5 mg) is approved for patients with advanced renal cell carcinoma (RCC) after one or more prior antiangiogenic therapies.

Objective: To assess whether a lower starting dose of lenvatinib has comparable efficacy with improved tolerability for patients with advanced RCC treated with lenvatinib plus everolimus.

Design, Setting, And Participants: A randomized, open-label, phase 2 global trial was conducted in patients with advanced clear cell RCC and disease progression after one prior vascular endothelial growth factor-targeted therapy (prior anti-programmed death-1/programmed death ligand-1 therapy permitted).

Treatment patterns, testing practices, and outcomes in the pre-FLAURA era for patients with EGFR mutation-positive advanced NSCLC: a retrospective chart review (REFLECT).

Introduction: For epidermal growth factor receptor mutation-positive (EGFRm) non-small-cell lung cancer (NSCLC), EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are the preferred first-line (1 L) treatment in the advanced setting. Osimertinib, a third-generation EGFR-TKI, received full approval in 2017 for second-line (2 L) treatment of EGFR T790M-positive NSCLC. The REFLECT study characterizes real-world treatment/testing patterns, attrition rates, and outcomes in patients with EGFRm advanced NSCLC treated with 1 L first-/second-generation (1G/2G) EGFR-TKIs before 1 L osimertinib approval.

Pathological complete response following cisplatin or carboplatin-based neoadjuvant chemotherapy for triple-negative breast cancer: A systematic review and meta-analysis.

The addition of platinum compounds to standard neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) is highly controversial. Platinum agents, such as cisplatin and carboplatin, are DNA-damaging agents which exhibit activity in breast cancer, particularly in the TNBC subgroup. In order to assess the efficacy of each most representative platinum agent (cisplatin and carboplatin) in patients with TNBC treated with NACT, the present study performed a systematic review and meta-analysis of all available published studies on TNBC.

Potential Biomarkers for the Efficacy of PD-1-PD-L Blockade in Cancer.

A decade ago, immune checkpoint blockade emerged as a major breakthrough in oncology, proposing a novel approach by which immune brakes could be released to enhance antitumor responses. Despite apparently modest improvement of the median duration of response, a spectacular doubling of long-term responses as compared to the available standard of care was seen, for instance, in metastatic melanoma. It soon became obvious that the percentage of patients responding to these novel approaches is relatively small, and the importance of an accurate prediction of responders became more and more clear.

Namodenoson in Advanced Hepatocellular Carcinoma and Child-Pugh B Cirrhosis: Randomized Placebo-Controlled Clinical Trial.

Namodenoson, an A3 adenosine-receptor agonist, showed promising results in advanced hepatocellular carcinoma (HCC) and moderate hepatic dysfunction (Child-Pugh B; CPB) in a phase I/II clinical study. This phase II study investigated namodenoson as second-line therapy in such patients. Patients were randomized 2:1 to twice a day (BID) namodenoson (25 mg; = 50) or placebo ( = 28).

Treatment patterns and real-world evidence for stage III non-small cell lung cancer in Central and Eastern Europe.

Background The aim of this project was to collect real-world evidence and describe treatment patterns for stage III non-small cell lung cancer in Central and Eastern Europe. Based on real-world evidence, an expert opinion was developed, and the unmet needs and quality indicators were identified. Patients and methods A systematic literature search and a multidisciplinary expert panel of 10 physicians from 7 countries used a modified Delphi process to identify quality indicators and unmet needs in patients with stage III non-small cell lung cancer.

Final Analysis of the Ipilimumab Versus Placebo Following Radiotherapy Phase III Trial in Postdocetaxel Metastatic Castration-resistant Prostate Cancer Identifies an Excess of Long-term Survivors.

Background: The phase 3 trial CA184-043 evaluated radiotherapy to bone metastases followed by Ipilimumab or placebo in men with metastatic castrate-resistant prostate cancer (mCRPC) who had received docetaxel previously. In a prior analysis, the trial's primary endpoint (overall survival [OS]) was not improved significantly.

Objective: To report the final analysis of OS.

Phase 3 Study of Palonosetron IV Infusion Vs. IV Bolus for Chemotherapy-Induced Nausea and Vomiting Prophylaxis After Highly Emetogenic Chemotherapy.

Context: Palonosetron (PALO) is one of the two active components of NEPA, the fixed-combination antiemetic comprising netupitant (oral)/fosnetupitant (IV) and PALO. To increase the convenience of NEPA administration, especially for patients with swallowing difficulties, an IV NEPA formulation has been developed, where PALO is administered as a 30-minute infusion instead of the approved 30-second bolus.

Objectives: To determine the efficacy and safety of the PALO component used in IV NEPA.

Clinical activity of a htert (vx-001) cancer vaccine as post-chemotherapy maintenance immunotherapy in patients with stage IV non-small cell lung cancer: final results of a randomised phase 2 clinical trial.

Background: The cancer vaccine Vx-001, which targets the universal tumour antigen TElomerase Reverse Transcriptase (TERT), can mount specific Vx-001/TERT CD8 + cytotoxic T cells; this immune response is associated with improved overall survival (OS) in patients with advanced/metastatic non-small cell lung cancer (NSCLC).

Methods: A randomised, double blind, phase 2b trial, in HLA-A*201-positive patients with metastatic, TERT-expressing NSCLC, who did not progress after first-line platinum-based chemotherapy were randomised to receive either Vx-001 or placebo. The primary endpoint of the trial was OS.

Access to Novel Drugs for Non-Small Cell Lung Cancer in Central and Southeastern Europe: A Central European Cooperative Oncology Group Analysis.

Background: Treatment of non-small cell lung cancer (NSCLC) improved substantially in the last decades. Novel targeted and immune-oncologic drugs were introduced into routine treatment. Despite accelerated development and subsequent drug registrations by the European Medicinal Agency (EMA), novel drugs for NSCLC are poorly accessible in Central and Eastern European (CEE) countries.

CheckMate 171: A phase 2 trial of nivolumab in patients with previously treated advanced squamous non-small cell lung cancer, including ECOG PS 2 and elderly populations.

Background: CheckMate 171 (NCT02409368) is an open-label, multicentre, phase 2 trial of nivolumab in previously treated advanced squamous non-small cell lung cancer (NSCLC), conducted as part of a post-approval commitment to the European Medicines Agency (EMA). We report outcomes from this trial.

Methods: Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 and disease progression during/after ≥1 systemic treatment (≥1 being platinum-based chemotherapy) for advanced or metastatic disease were treated with nivolumab 3 mg/kg every 2 weeks until progression or unacceptable toxicity.

Association of baseline absolute neutrophil counts and survival in patients with metastatic colorectal cancer treated with second-line antiangiogenic therapies: exploratory analyses of the RAISE trial and validation in an electronic medical record data set.

Background: In the RAISE trial, ramucirumab+leucovorin/fluorouracil/irinotecan (FOLFIRI) improved the median overall survival (mOS) of patients with previously treated metastatic colorectal cancer versus patients treated with placebo+FOLFIRI but had a higher incidence of neutropaenia, leading to more chemotherapy dose modifications and discontinuations. Thus, we conducted an exploratory post-hoc analysis of RAISE and a retrospective, observational analysis of electronic medical record (EMR) data to determine and verify the association of neutropaenia, baseline absolute neutrophil count (ANC) and survival.

Methods: The RAISE analysis used the study safety population (n=1057).

Efficacy and Safety of Necitumumab Continuation Therapy in the Phase III SQUIRE Study of Patients With Stage IV Squamous Non-Small-Cell Lung Cancer.

Introduction: In a retrospective analysis of the SQUamous NSCLC treatment with the Inhibitor of EGF REceptor (SQUIRE) study, we investigated the efficacy and safety of single-agent necitumumab continuation therapy in patients with stage IV squamous non-small-cell lung cancer and in a subpopulation of patients with epidermal growth factor receptor (EGFR)-expressing tumors.

Patients And Methods: Patients were randomized 1:1 for ≤ 6 cycles of gemcitabine and cisplatin either with or without necitumumab. Patients who received necitumumab continued receiving single-agent necitumumab until progressive disease (necitumumab continuation).

Effectiveness and safety profile of ipilimumab therapy in previously treated patients with unresectable or metastatic melanoma - the Romanian Patient Access Program.

Purpose: The Romanian Patient Access Program (Ro-PAP, CA 184-427), part of the European Expanded Access Program (EAP), was developed to evaluate the effectiveness and safety profile ipilimumab in previously treated patients with advanced melanoma (unresectable or metastatic melanoma). The objective of our retrospective observational study of patients included in this program was to provide data recorded in real-life settings.

Methods: We analysed 89 patients enrolled in Ro-PAP, CA 184-427 (54 men and 35 women) aged between 29 and 89 years.

Prevalent somatic BRCA1 mutations shape clinically relevant genomic patterns of nasopharyngeal carcinoma in Southeast Europe.

Genomic patterns of nasopharyngeal carcinomas (NPCs) have as yet been studied in Southeast Asian (SEA) patients. Here, we investigated genomic patterns of locally advanced NPC Southeast European (SEE) patients treated with chemoradiotherapy. We examined 126 tumors (89% EBV positive) from Greek and Romanian NPC patients with massively parallel sequencing.