Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non-Small-Cell Lung Cancer.

Purpose: Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting.

Patients And Methods: This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.

Biomarker expression and survival in patients with non-small cell lung cancer receiving adjuvant chemotherapy in Denmark.

Introduction: Programmed cell death ligand-1 (PD-L1) expression may help identify patients with non-small cell lung cancer (NSCLC) who would benefit from immunotherapy. We assessed PD-L1 expression, and epidermal growth factor receptor (EGFR) and V-Ki-Ras2 Kirsten rat sarcoma (KRAS) mutations in NSCLC patients receiving adjuvant chemotherapy.

Methods: Data for stage IB/II/IIIA NSCLC patients (diagnosed: 2001-2012) were retrieved from Danish population-based registries.

Association between Health-Related Quality of Life and Completion of First-Line Treatment among Lung Cancer Patients.

Experts recommend assessing lung cancer patients' health-related quality of life (HRQOL) in the diagnostic evaluation. We investigated the association between HRQOL and completion of first-line treatment among lung cancer patients in a prospective cohort study. Clinical information on lung cancer patients was obtained from medical records, and information on quality of life and lung cancer-related symptoms was obtained through questionnaires at time of diagnosis.

Osimertinib in non-small cell lung cancer with uncommon -mutations: a subgroup analysis with pooled data from two phase II clinical trials.

Background: Osimertinib is standard of care for -mutated non-small cell lung cancer (NSCLC) patients. The efficacy of the drug in patients with mutations other than the common deletion in exon 19 and L858R in exon 21 is largely unknown.

Methods: We identified patients with uncommon -mutations from two prospective clinical phase II, single-arm studies for previously treated patients and untreated patients, respectively, and pooled data for this analysis.

Impact of MET status on treatment outcomes in papillary renal cell carcinoma: A pooled analysis of historical data.

Background: Papillary renal cell carcinoma (PRCC) represents 15% of RCCs but has no indicated therapies, with limited biomarker-based data to inform targeted treatment. MET alterations may be key; > 80% of PRCC tumours show MET upregulation. The objective of this study was to assess MET status in PRCC and its impact on clinical outcomes.

Intracranial effect of osimertinib in relapsed -mutated T790M-positive and -negative non-small cell lung cancer patients: results from a phase II study.

Introduction: Osimertinib is effective for relapsed T790M-positive patients with brain metastases. The high brain permeability suggests that also such patients without T790M could benefit. Therefore, we evaluated the effect of osimertinib on brain metastases in both T790M-positive and -negative patients.

Detection and characterization of lung cancer using cell-free DNA fragmentomes.

Non-invasive approaches for cell-free DNA (cfDNA) assessment provide an opportunity for cancer detection and intervention. Here, we use a machine learning model for detecting tumor-derived cfDNA through genome-wide analyses of cfDNA fragmentation in a prospective study of 365 individuals at risk for lung cancer. We validate the cancer detection model using an independent cohort of 385 non-cancer individuals and 46 lung cancer patients.

PD-L1 expression, EGFR and KRAS mutations and survival among stage III unresected non-small cell lung cancer patients: a Danish cohort study.

Programmed cell death receptor ligand-1 (PD-L1) expression, KRAS (KRASm) and EGFR (EGFRm) mutations may influence non-small cell lung cancer (NSCLC) prognosis. We aimed to evaluate PD-L1 expression, KRASm, and EGFRm and survival among stage III unresected NSCLC patients. Using Danish registries, we collected data on stage III unresected NSCLC patients diagnosed 2001-2012 and paraffin-embedded tumor tissue from pathology archives.

Programmed cell death ligand-1 expression and survival in a cohort of patients with non-small cell lung cancer receiving first-line through third-line therapy in Denmark.

Background: PD-L1 expression on tumor cells (TCs) or immune cells (ICs) may be used as a prognostic marker for survival in patients with NSCLC. We characterized PD-L1 expression on TCs or ICs in a patient cohort with NSCLC to determine associations between PD-L1 expression and overall survival (OS), according to EGFR and KRAS mutation status.

Methods: Danish patients aged >18 years diagnosed with NSCLC before 2014 on first- (N = 491), second- (N = 368), or third-line (N = 498) therapy were included.

Savolitinib ± Osimertinib in Japanese Patients with Advanced Solid Malignancies or EGFRm NSCLC: Ph1b TATTON Part C.

Background: Preliminary data suggest that combining savolitinib, a potent and highly selective MET-tyrosine kinase inhibitor (TKI), with osimertinib, a third-generation, irreversible, oral epidermal growth factor receptor-TKI (EGFR-TKI), may overcome MET-based resistance to EGFR-TKIs.

Objective: To investigate the safety and tolerability of savolitinib in Japanese patients with advanced solid malignancies.

Patients And Methods: In Part C of the phase Ib, multi-arm, open-label, multicenter TATTON study, two cohorts of Japanese adult patients were evaluated across six study centers in Japan.

A Randomized, Double-Blind, Placebo- and Positive-Controlled, Three-Way Crossover Study in Healthy Participants to Investigate the Effect of Savolitinib on the QTc Interval.

Savolitinib (AZD6094, HMPL-504, volitinib) is an oral, bioavailable, selective MET-tyrosine kinase inhibitor. This randomized, double-blind, 3-way, crossover phase 1 study of savolitinib versus moxifloxacin (positive control) and placebo-evaluated effects on the QT interval after a single savolitinib dose. Healthy non-Japanese men were randomized to 1 of 6 treatment sequences, receiving single doses of savolitinib 600 mg, moxifloxacin 400 mg, and placebo.

A phase Ib study of the highly selective MET-TKI savolitinib plus gefitinib in patients with EGFR-mutated, MET-amplified advanced non-small-cell lung cancer.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are recommended first-line treatments in EGFR-mutated (EGFRm) non-small-cell lung cancer (NSCLC). However, acquired resistance (e.g.

Efficacy of Savolitinib vs Sunitinib in Patients With MET-Driven Papillary Renal Cell Carcinoma: The SAVOIR Phase 3 Randomized Clinical Trial.

Importance: Papillary renal cell carcinoma (PRCC) is the most common type of non-clear cell RCC. Because some cases of PRCC are MET-driven, MET inhibition could be a targeted treatment approach. In previous studies, savolitinib (AZD6094, HMPL-504, volitinib), a highly selective MET-tyrosine kinase inhibitor, demonstrated antitumor activity in this patient group.

Protein-altering germline mutations implicate novel genes related to lung cancer development.

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.

Osimertinib in T790M-positive and -negative patients with EGFR-mutated advanced non-small cell lung cancer (the TREM-study).

Objectives: In non-small cell lung cancer patients with acquired resistance to first- or second-generation EGFR-TKIs, osimertinib is approved in the presence of the T790 M resistance mutation. We assessed the efficacy of osimertinib in both T790M-positive and T790M-negative patients.

Materials And Methods: The TREM-study is an investigator-initiated, multi-centre, single-arm, phase 2 clinical trial conducted in five Northern European countries.

Optimizing COPD treatment in patients with lung- or head and neck cancer does not improve quality of life - a randomized, pilot, clinical trial.

: Chronic obstructive pulmonary disease (COPD) is a common comorbidity in patients with lung and head- and neck cancer. Patients with lung cancer who also suffer from COPD have a worse prognosis than patients with lung cancer and no COPD. It has previously been shown that diagnosis and treatment of concomitant COPD in patients with newly diagnosed lung- or head and neck cancer need optimization.

Osimertinib plus savolitinib in patients with EGFR mutation-positive, MET-amplified, non-small-cell lung cancer after progression on EGFR tyrosine kinase inhibitors: interim results from a multicentre, open-label, phase 1b study.

Background: Preclinical data suggest that EGFR tyrosine kinase inhibitors (TKIs) plus MET TKIs are a possible treatment for EGFR mutation-positive lung cancers with MET-driven acquired resistance. Phase 1 safety data of savolitinib (also known as AZD6094, HMPL-504, volitinib), a potent, selective MET TKI, plus osimertinib, a third-generation EGFR TKI, have provided recommended doses for study. Here, we report the assessment of osimertinib plus savolitinib in two global expansion cohorts of the TATTON study.

ALK immunohistochemistry positive, FISH negative NSCLC is infrequent, but associated with impaired survival following treatment with crizotinib.

Objective: Metastasized non-small cell lung cancer (NSCLC) with an anaplastic lymphoma kinase (ALK) rearrangement is usually sensitive to a range of ALK-tyrosine kinase inhibitors. ALK-positive NSCLC have been identified in pivotal phase III trials with fluorescence in situ hybridization (ALK FISH+). These tumors are also expressing the fusion product (ALK immunohistochemistry (IHC)+).

AHRR (cg05575921) methylation extent of leukocyte DNA and lung cancer survival.

Background: Prior studies have shown that AHRR (cg05575921) hypomethylation may be a marker of smoking, lung cancer risk and potentially lung cancer survival (in some lung cancer subtypes). It is unknown if AHRR (cg05575921) hypomethylation is associated with reduced survival among lung cancer patients.

Methods: In bisulfite treated leukocyte DNA from 465 lung cancer patients from the Copenhagen prospective lung cancer study, we measured AHRR (cg05575921) methylation.

[Medical treatment of lung cancer].

Lung cancer causes most cancer-related deaths in the western world. In Denmark, over 4,700 cases of lung cancer are diagnosed annually. The medical treatment of lung cancer has undergone a significant development over the past 20 years.

Durable Clinical Responses and Long-Term Follow-Up of Stage III-IV Non-Small-Cell Lung Cancer (NSCLC) Patients Treated With IDO Peptide Vaccine in a Phase I Study-A Brief Research Report.

Long-term follow-up on a clinical trial of 15 stage III-IV NSCLC patients treated with an Indoleamine 2,3-Dioxygenase (IDO) peptide vaccine (NCT01219348). Fifteen HLA-A2-positive patients with stable stage III-IV NSCLC after standard chemotherapy were treated with subcutaneous vaccinations (100 μg IDO5 peptide, sequence ALLEIASCL, formulated in 900 μl Montanide) biweekly for 2.5 months and thereafter monthly until progression or up to 5 years.

Change in non-small-cell lung cancer tumor size in patients treated with nintedanib plus docetaxel: analyses from the Phase III LUME-Lung 1 study.

Background: Nintedanib in combination with docetaxel is approved in the European Union and other countries for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) of adenocarcinoma histology after first-line chemotherapy, based on the overall survival findings of Phase III LUME-Lung 1 study. Change in target lesion size over time as a treatment effect was assessed in patients from this study.

Methods: Tumor size was evaluated using predefined tumor measurements.

Assessing the pattern of recurrence in Danish stage I lung cancer patients in relation to the follow-up program: are we failing to identify patients with cerebral recurrence?

Background: There is paucity of evidence regarding the optimal follow-up (FU) regimen for lung cancer. Consequently, FU is organized differently across countries. The Danish FU regimen has short FU intervals with a computed tomography (CT) scan of the chest and upper abdomen every three months in the early phase (first 2 years), then every six months in the late phase of FU (3rd, 5th year).