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.

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.

A Molecular Epidemiological Analysis Of Programmed Cell Death Ligand-1 (PD-L1) Protein Expression, Mutations And Survival In Non-Small Cell Lung Cancer.

Purpose: To characterize programmed cell death ligand-1 (PD-L1) expression in relation to survival and gene mutation status in patients with advanced NSCLC. The study also explored the influence of tumor mutational burden (TMB) on PD-L1 expression and patient characteristics.

Patients And Methods: Adult patients with histologically or cytologically documented Stage IIIB/Stage IV/recurrent/progressive NSCLC, Eastern Cooperative Oncology Group performance status 0 to 3, and >2 lines of prior systemic treatment regimens were included in this retrospective analysis.

ASTRIS: a global real-world study of osimertinib in >3000 patients with T790M positive non-small-cell lung cancer.

Osimertinib is a third-generation, irreversible, oral EGFR tyrosine kinase inhibitor. We report real-world effectiveness and safety data. T790M positive advanced non-small-cell lung cancer adults, who received ≥1 prior EGFR tyrosine kinase inhibitor, received osimertinib 80 mg daily.

Complications and Economic Burden Associated With Obtaining Tissue for Diagnosis and Molecular Analysis in Patients With Non-Small-Cell Lung Cancer in the United States.

Purpose: With an increase in biomarker-directed therapies, tissue biopsy to identify targetable genomic and immunologic alterations has become the mainstay of managing patients with non-small-cell lung cancer (NSCLC); however, little is known about the associated economic impact and complication rate. This study assesses the frequency, complications, and costs of diagnostic and postprogression biopsy.

Methods: This retrospective, observational study was conducted using administrative claims data from more than 30 million commercially insured individuals in the United States (2006 to 2014).

A phase I/II study of bexarotene with carboplatin and weekly paclitaxel for the treatment of patients with advanced non-small cell lung cancer.

Background: Rexinoids demonstrate anti-proliferative differentiation-inducing activity in multiple cancer types, including NSCLC. Prior studies have shown promising results when combining rexinoids with chemotherapy. This phase I/II study evaluates the tolerability and activity of a rexinoid, bexarotene, combined with weekly paclitaxel and monthly carboplatin.

Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial.

Background: BRAF mutations act as an oncogenic driver via the mitogen-activated protein kinase (MAPK) pathway in non-small cell lung cancer (NSCLC). BRAF inhibition has shown antitumour activity in patients with BRAF(V600E)-mutant NSCLC. Dual MAPK pathway inhibition with BRAF and MEK inhibitors in BRAF(V600E)-mutant NSCLC might improve efficacy over BRAF inhibitor monotherapy based on observations in BRAF(V600)-mutant melanoma.

Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer.

Background: Treatment options for patients with non-small cell lung cancer (NSCLC) with brain metastases are limited. Patupilone (EPO906), a blood-brain barrier-penetrating, microtubule-targeting, cytotoxic agent, has shown clinical activity in phase 1/2 studies in patients with NSCLC. This study evaluates the efficacy, pharmacokinetics, and safety of patupilone in NSCLC brain metastases.

VATS lobectomy facilitates the delivery of adjuvant docetaxel-carboplatin chemotherapy in patients with non-small cell lung cancer.

Background: To evaluate the safety and tolerability of docetaxel/carboplatin regimen in the post-operative setting of patients with non-small cell lung cancer (NSCLC).

Methods: Enrolment of 133 patients with stage Ib - IIIa NSCLC was undertaken in an open-label, single arm study to assess the safety and tolerability of docetaxel (75 mg/kg) and carboplatin (AUC 5.5) administered for 3 cycles after resection for curative intent.

Quantitative phosphoproteomic profiling of human non-small cell lung cancer tumors.

Unlabelled: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Within the molecular scope of NCSLC, a complex landscape of dysregulated cellular signaling has emerged, defined largely by mutations in select mediators of signal transduction, including the epidermal growth factor receptor (EGFR) and anaplastic lymphoma (ALK) kinases. Consequently, these mutant kinases become constitutively activated and targets for chemotherapeutic intervention.

Epidermal growth factor receptor tyrosine kinase inhibitors as initial therapy for non-small cell lung cancer: focus on epidermal growth factor receptor mutation testing and mutation-positive patients.

Activation of the epidermal growth factor receptor (EGFR) pathway has been implicated in tumorigenesis in non-small cell lung cancer (NSCLC), the most common type of lung cancer. As a result, EGFR has become a key focus for the development of personalized therapy, with several molecular biomarkers having been investigated as potential predictors of response with EGFR tyrosine kinase inhibitors (TKIs) in NSCLC (e.g.

Adenocarcinoma contains more immune tolerance regulatory t-cell lymphocytes (versus squamous carcinoma) in non-small-cell lung cancer.

Background: Regulatory T lymphocytes (Tregs) are known to have host-immune dampening effects in many tumors and to be associated with increased tumor recurrence. Pharmacologic therapies have been developed to target these cells and hence strengthen the host's immune system. The FoxP3 gene is a marker of Tregs and can be visualized with immunohistochemistry (IHC).

Trimodality therapy for stage II-III carcinoma of the esophagus: a dose-ranging study of concurrent capecitabine, docetaxel, and thoracic radiotherapy.

Purpose: This dose-escalation study was performed to determine the recommended phase II dose of oral capecitabine to be delivered concurrently with thoracic radiation therapy and weekly docetaxel in patients with locally advanced esophageal carcinoma.

Methods: Patients with operable stage II or III esophageal carcinoma were staged by endoscopic ultrasonography and computed tomography. Two cycles of docetaxel (80 mg/m) and carboplatin (target area under the concentration-time curve: 6 mg/ml × min) were delivered over 6 weeks.

A phase I trial and in vitro studies combining ABT-751 with carboplatin in previously treated non-small cell lung cancer patients.

Background: ABT-751 is a novel antimitotic agent that exerted cytotoxic effects in preclinical studies. Carboplatin has efficacy in treating advanced non-small cell lung cancer (NSCLC) in combination with other drugs.

Methods: Lung cancer cell lines were treated with ABT-751 and/or carboplatin to investigate their impact on cell growth.

A humanized anti-IL-6 antibody (ALD518) in non-small cell lung cancer.

Introduction: Inflammatory pathways may be an important contributor to morbidity and mortality associated with lung cancer. The oncogene-associated inflammatory microenvironment leads to production of inflammatory cytokines such as IL-6. IL-6 is associated with poor prognosis and correlates with debilitating lung-cancer-related symptoms such as fatigue, thromboembolism, cachexia and anemia.

Cytomorphologic features of advanced lung adenocarcinomas tested for EGFR and KRAS mutations: a retrospective review of 50 cases.

Associations between bronchioloalveolar carcinoma (BAC), mucinous differentiation, and epidermal growth factor receptor (EGFR) and KRAS mutations have been previously reported in studies of surgical specimens. We present the cytomorphology of lung adenocarcinomas, including metastases that were diagnosed by cytologic methods and the relationship to both EGFR and KRAS mutational status. We retrospectively reviewed the clinical and cytomorphologic features of 50 lung adenocarcinomas that were tested for both EGFR and KRAS mutations.

Bexarotene plus erlotinib suppress lung carcinogenesis independent of KRAS mutations in two clinical trials and transgenic models.

The rexinoid bexarotene represses cyclin D1 by causing its proteasomal degradation. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib represses cyclin D1 via different mechanisms. We conducted a preclinical study and 2 clinical/translational trials (a window-of-opportunity and phase II) of bexarotene plus erlotinib.

Prognostic and predictive value of epidermal growth factor receptor tyrosine kinase domain mutation status and gene copy number for adjuvant chemotherapy in non-small cell lung cancer.

Purpose: Patients with non-small cell lung carcinoma with epidermal growth factor receptor (EGFR) mutations may have a more favorable prognosis and greater response to chemotherapy. The effect of EGFR mutation and gene copy on patients with early-stage non-small cell lung carcinoma receiving adjuvant chemotherapy has not been reported.

Patients And Methods: Tumor samples from NCIC Clinical Trials Group JBR.

Pemetrexed in advanced non-small-cell lung cancer.

Importance Of The Field: Current therapeutic options for advanced non-small-cell lung cancer (NSCLC) yield relatively modest improvements in survival leading to an ongoing search for new active treatment agents. In the past decade, pemetrexed has had an increasingly established role in the treatment of advanced NSCLC in both first- and second-line settings.

Areas Covered In This Review: Currently available published data on mechanism of action, pharmacokinetics, safety and efficacy of pemetrexed in the treatment of advanced NSCLC are described.

A dose escalation trial of biweekly docetaxel and gemcitabine with filgrastim or pegfilgrastim for the treatment of patients with advanced solid tumors.

Background/aims: A single-institution phase I trial to determine the feasibility of using filgrastim or pegfilgrastim to increase the dose intensity of biweekly docetaxel and gemcitabine.

Methods: Patients with metastatic solid tumors received gemcitabine 3,000 mg/m(2) and increasing doses of docetaxel (55 mg/m(2) in 10 mg/m(2) increments) every 14 days with filgrastim or pegfilgrastim.

Results: 35 patients enrolled, median 2 prior therapies, 158 cycles of therapy.

Randomized phase II multicenter trial of two schedules of lapatinib as first- or second-line monotherapy in patients with advanced or metastatic non-small cell lung cancer.

Purpose: This randomized phase II study was initially designed to test the activity of two dose schedules of lapatinib (GW572016H), an oral, reversible, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2/neu; HER2), in chemotherapy-naive patients with non-small cell lung cancer (NSCLC); it was later amended to target patients with bronchioloalveolar carcinoma or no smoking history.

Experimental Design: Patients with good performance status and recurrent or metastatic NSCLC were randomized to lapatinib (orally, 1,500 mg once daily or 500 mg twice daily) until progression or intolerance. Patients could have had a maximum of one prior systemic therapy (chemotherapy or biological therapy) for NSCLC.

Lung cancer in a U.S. population with low to moderate arsenic exposure.

Background: Little is known about the carcinogenic potential of arsenic in areas with low to moderate concentrations of arsenic (< 100 microg/L) in drinking water.

Objectives: We examined associations between arsenic and lung cancer.

Methods: A population-based case-control study of primary incident lung cancer was conducted in 10 counties in two U.

Phase II study of the proteasome inhibitor bortezomib (PS-341, Velcade) in chemotherapy-naïve patients with advanced stage non-small cell lung cancer (NSCLC).

The primary objective of this study was to determine the objective response rate of bortezomib as a first-line therapy in patients advanced stage NSCLC. Advanced/metastatic NSCLC patients with measurable disease, adequate organ function, ECOG performance status of 0-2, and no prior chemotherapy for metastatic disease were eligible. Patients received intravenously bolus bortezomib 1.

Prognostic and predictive importance of p53 and RAS for adjuvant chemotherapy in non small-cell lung cancer.

Purpose: p53 and RAS are multifunctional proteins that are critical to cell cycle regulation, apoptosis, cell survival, gene transcription, response to stress, and DNA repair. We have evaluated the prognostic and predictive value of p53 gene/protein aberrations using tumor samples from JBR.10, a North American phase III intergroup trial that randomly assigned 482 patients with completely resected stage IB and II non-small-cell lung cancer (NSCLC) to receive four cycles of adjuvant cisplatin plus vinorelbine or observation alone.

Current treatment paradigms for locally advanced non-small cell lung cancer.

Locally advanced non-small cell lung cancer (NSCLC) is a multifaceted disease that is challenging to manage. The majority of patients can be appropriately treated with a combination of chemotherapy and radiation therapy; however, a subset of stage III patients who are considered surgical candidates may require a modification of this plan. For example, a trimodal approach using chemoradiation followed by surgery may be beneficial for fit patients with bulky mediastinal disease who are candidates for lobectomy, whereas patients with minimal mediastinal nodal involvement may receive only chemotherapy before surgical resection.