Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial.

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance-which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment-and developing effective therapies to overcome them, remains an unmet need.

Histologic and Genotypic Characterization of Lung Cancer in the Inuit Population of the Eastern Canadian Arctic.

Inuit are the Indigenous Arctic peoples and residents of the Canadian territory of Nunavut who have the highest global rate of lung cancer. Given lung cancer's mortality, histological and genomic characterization was undertaken to better understand the disease biology. We retrospectively studied all Inuit cases from Nunavut's Qikiqtani (Baffin) region, referred to the Ottawa Hospital Cancer Center between 2001 and 2011.

Novel Nanoparticle-Based Cancer Treatment, Effectively Inhibits Lung Metastases and Improves Survival in a Murine Breast Cancer Model.

Sarah Nanoparticles (SaNPs) are unique multicore iron oxide-based nanoparticles, developed for the treatment of advanced cancer, following standard care, through the selective delivery of thermal energy to malignant cells upon exposure to an alternating magnetic field. For their therapeutic effect, SaNPs need to accumulate in the tumor. Since the potential accumulation and associated toxicity in normal tissues are an important risk consideration, biodistribution and toxicity were assessed in naïve BALB/c mice.

CCTG BR34: A Randomized Phase 2 Trial of Durvalumab and Tremelimumab With or Without Platinum-Based Chemotherapy in Patients With Metastatic NSCLC.

Introduction: First-line therapy for patients with metastatic NSCLC includes checkpoint inhibitor monotherapy, dual checkpoint inhibition, or combination with chemotherapy. We compared outcomes with combination chemoimmunotherapy versus dual checkpoint inhibition as first-line treatment for patients with metastatic NSCLC.

Methods: This open-label, randomized clinical trial was conducted at 44 sites in Canada and Australia.

Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung: Final analysis of the randomised phase 3 LUX-Lung 8 trial.

Background: LUX-Lung 8 was a randomised, controlled, phase 3 study comparing afatinib and erlotinib as second-line treatment of patients with advanced squamous cell carcinoma (SCC) of the lung. We report the final overall survival (OS) and safety analyses of LUX-Lung 8 and investigate the characteristics of patients who achieved long-term benefit (≥12 months' treatment).

Methods: LUX-Lung 8 (NCT01523587) enroled patients between March 2012 and January 2014 in 183 cancer centres located in 23 countries worldwide and this final analysis had a data cut-off of March 2018.

Tumor genomic, transcriptomic, and immune profiling characterizes differential response to first-line platinum chemotherapy in high grade serous ovarian cancer.

Background: In high grade serous ovarian cancer (HGSOC), there is a spectrum of sensitivity to first line platinum-based chemotherapy. This study molecularly characterizes HGSOC patients from two distinct groups of chemotherapy responders (good vs. poor).

A phase IB study of durvalumab with or without tremelimumab and platinum-doublet chemotherapy in advanced solid tumours: Canadian Cancer Trials Group Study IND226.

This multicenter phase Ib study aimed to establish a recommended phase II dose for durvalumab (Du) ± tremelimumab (Tr) in combination with standard platinum-doublet chemotherapy. Eligible patients were enrolled into one of six dose levels (DL) of Du ± Tr which included concomitant treatment with standard platinum-doublet regimens; (pemetrexed, gemcitabine, etoposide, (each with cisplatin or carboplatin) or nab-paclitaxel (with carboplatin)). Dose escalation was according to a Rolling Six type design.

A novel, more reliable approach to use of progression-free survival as a predictor of gain in overall survival: The Ottawa PFS Predictive Model.

Progression-free survival (PFS) hazard ratios and gain in median PFS are suggested predictors of overall survival (OS) gain (with gain defined as experimental arm minus control arm values). We assessed use of half-lives (time to progression/death of half remaining patients). We reviewed randomized trials from Journal of Clinical Oncology and New England Journal of Medicine, 01/2012-06/12/2017 (discovery series) and 01/01/2007-12/31/2011 (first validation series).

Third-generation epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small cell lung cancer.

Mutations in the epidermal growth factor receptor () gene are the most common targetable genomic drivers of non-small cell lung cancer (NSCLC), occurring in approximately 50% and 10-15% of adenocarcinomas of the lung in Asian and Western populations, respectively. The most common EGFR-activating mutations, the exon 19 deletion and the L858R point mutation occurring in the receptor tyrosine kinase domain, are susceptible to inhibition. The first EGFR tyrosine kinase inhibitors (TKIs) to be evaluated were the reversible first-generation EGFR TKIs, gefitinib and erlotinib, followed by the irreversible second-generation EGFR TKIs, afatinib and dacomitinib.

Selumetinib in patients receiving standard pemetrexed and platinum-based chemotherapy for advanced or metastatic KRAS wildtype or unknown non-squamous non-small cell lung cancer: A randomized, multicenter, phase II study. Canadian Cancer Trials Group (CCTG) IND.219.

Introduction: Activation of the RAS/RAF/MEK/ERK pathway may confer resistance to chemotherapy in non-small cell lung cancer (NSCLC). Selumetinib (AZD6244, ARRY142886), a MEK1/2 inhibitor combined with chemotherapy in patients with NSCLC was evaluated in two schedules to evaluate efficacy and toxicity.

Methods: IND.

Safety, Efficacy, and Patient-Reported Health-Related Quality of Life and Symptom Burden with Nivolumab in Patients with Advanced Non-Small Cell Lung Cancer, Including Patients Aged 70 Years or Older or with Poor Performance Status (CheckMate 153).

Introduction: CheckMate 153 (NCT02066636) is a phase 3B/4 study assessing nivolumab in previously treated patients with advanced NSCLC. Eligibility criteria allowed enrollment of patients with poor prognostic features of advanced age or diminished Eastern Cooperative Oncology Group performance status (ECOG PS), which are typically underrepresented in or excluded from randomized controlled trials.

Methods: Patients with stage IIIB or IV NSCLC and an ECOG PS of 0 to 2 with disease progression after at least one systemic therapy received nivolumab (3 mg/kg every 2 weeks) until progression, unacceptable toxicity, or consent withdrawal.

Inpatients versus outpatients with advanced non-small cell lung cancer: Characteristics and outcomes.

Background: Most newly diagnosed advanced NSCLC patients have an initial medical oncology consult as an outpatient. Sometimes, the initial consult occurs as an inpatient. We explored differences among NSCLC patients presenting to medical oncology while hospitalized versus as outpatients.

Osimertinib in patients with T790M mutation-positive, advanced non-small cell lung cancer: Long-term follow-up from a pooled analysis of 2 phase 2 studies.

Background: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is selective for both EGFR-TKI-sensitizing and T790M (threonine-to-methionine substitution at codon 790)-resistance mutations. The authors present long-term follow-up data from a preplanned, pooled analysis of phase 2 studies, the AZD9291 First Time in Patients Ascending Dose Study (AURA) extension trial (clincialtrials.gov identifier NCT01802632) and the AURA2 trial (NCT02094261).

Apixaban to Prevent Venous Thromboembolism in Patients with Cancer.

Background: Patients with active cancer have an increased risk of venous thromboembolism, which results in substantial morbidity, mortality, and health care expenditures. The Khorana score (range, 0 to 6, with higher scores indicating a higher risk of venous thromboembolism) has been validated to identify patients with cancer at elevated risk for this complication and may help select those who could benefit from thromboprophylaxis.

Methods: We conducted a randomized, placebo-controlled, double-blind clinical trial assessing the efficacy and safety of apixaban (2.

Association of ERBB Mutations With Clinical Outcomes of Afatinib- or Erlotinib-Treated Patients With Lung Squamous Cell Carcinoma: Secondary Analysis of the LUX-Lung 8 Randomized Clinical Trial.

Importance: Treatment choice for lung squamous cell carcinoma could be aided by identifying predictive biomarkers.

Objective: To assess whether patient outcomes in the LUX-Lung 8 trial were associated with ERBB gene family member aberrations in tumor specimens.

Design, Setting, And Participants: Ad hoc secondary analysis of the LUX-Lung 8 trial conducted at 183 centers in 23 countries from March 30, 2012, to January 30, 2014.

Canadian Cancer Trials Group (CCTG) IND211: A randomized trial of pelareorep (Reolysin) in patients with previously treated advanced or metastatic non-small cell lung cancer receiving standard salvage therapy.

Objectives: Pelareorep (reolysin), a Dearing strain of reovirus serotype 3, has demonstrated oncolytic activity as single agent and synergy with chemotherapy. We evaluated pelareorep, combined with standard second-line chemotherapy in patients with non-small cell lung cancer (NSCLC).

Materials And Methods: This randomized phase II trial enrolled patients with advanced or metastatic NSCLC after first line chemotherapy.

Update on International Cooperative Groups Studies in Thoracic Malignancies: The Emergence of Immunotherapy.

Cancer cooperative groups have historically played a critical role in the advancement of non-small-cell lung cancer therapy. Representatives from cooperative groups worldwide convene at the International Lung Cancer Congress annually. The International Lung Cancer Congress had its 17th anniversary in the summer of 2016.

Efficacy and safety results of depatuxizumab mafodotin (ABT-414) in patients with advanced solid tumors likely to overexpress epidermal growth factor receptor.

Background: Epidermal growth factor receptor (EGFR) alterations are associated with multiple cancers. Current EGFR-directed therapies have led to increased efficacy but are associated with specific side effects. The antibody-drug conjugate depatuxizumab mafodotin (depatux-m) targets EGFR with a monoclonal antibody linked to a cytotoxin, and is highly tumor-specific.

Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study.

Background: Results from retrospective studies indicate that selecting individuals for low-dose CT lung cancer screening on the basis of a highly predictive risk model is superior to using criteria similar to those used in the National Lung Screening Trial (NLST; age, pack-year, and smoking quit-time). We designed the Pan-Canadian Early Detection of Lung Cancer (PanCan) study to assess the efficacy of a risk prediction model to select candidates for lung cancer screening, with the aim of determining whether this approach could better detect patients with early, potentially curable, lung cancer.

Methods: We did this single-arm, prospective study in eight centres across Canada.

A phase I study of foretinib plus erlotinib in patients with previously treated advanced non-small cell lung cancer: Canadian cancer trials group IND.196.

Purpose: MET and AXL mediate resistance to EGFR TKI in NSCLC. Foretinib, a MET/RON/AXL/TIE-2/VEGFR kinase inhibitor may overcome EGFR kinase resistance. This dose escalation study combined foretinib and erlotinib in advanced pretreated NSCLC patients.

Symptom and Quality of Life Improvement in LUX-Lung 8, an Open-Label Phase III Study of Second-Line Afatinib Versus Erlotinib in Patients With Advanced Squamous Cell Carcinoma of the Lung After First-Line Platinum-Based Chemotherapy.

Introduction: In the phase III LUX-Lung 8 trial, afatinib significantly improved progression-free survival (PFS) and overall survival (OS) versus erlotinib in patients with squamous cell carcinoma (SCC) of the lung progressing during or after platinum-based chemotherapy. Patient-reported outcomes (PROs) and health-related quality of life (QoL) in these patients are presented.

Patients And Methods: Patients (n = 795) were randomized 1:1 to oral afatinib (40 mg/d) or erlotinib (150 mg/d).

Evaluation of the VeriStrat serum protein test in patients with advanced squamous cell carcinoma of the lung treated with second-line afatinib or erlotinib in the phase III LUX-Lung 8 study.

Objectives: Identification of biomarkers associated with clinical benefit may be crucial in establishing optimal treatment choice for patients with squamous cell carcinoma (SCC) of the lung after first-line chemotherapy. In this study, the ability of the VeriStrat serum protein test to predict differential clinical benefit with afatinib versus erlotinib, and the association of VeriStrat status with clinical outcomes irrespective of EGFR-TKI used, was assessed in a retrospective analysis of the phase III LUX-Lung 8 trial.

Materials And Methods: Pretreatment plasma samples were analyzed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

The Cost-Effectiveness of High-Risk Lung Cancer Screening and Drivers of Program Efficiency.

Introduction: Lung cancer risk prediction models have the potential to make programs more affordable; however, the economic evidence is limited.

Methods: Participants in the National Lung Cancer Screening Trial (NLST) were retrospectively identified with the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The high-risk subgroup was assessed for lung cancer incidence and demographic characteristics compared with those in the low-risk subgroup and the Pan-Canadian Early Detection of Lung Cancer Study (PanCan), which is an observational study that was high-risk-selected in Canada.

Plasma ctDNA Analysis for Detection of the EGFR T790M Mutation in Patients with Advanced Non-Small Cell Lung Cancer.

Introduction: Tumor biopsies for detecting EGFR mutations in advanced NSCLC are invasive, costly, and not always feasible for patients with late-stage disease. The clinical utility of the cobas EGFR Mutation Test v2 (Roche Molecular Systems, Inc., Pleasanton, CA) with plasma samples from patients with NSCLC at disease progression after previous EGFR tyrosine kinase inhibitor therapy was investigated to determine eligibility for osimertinib treatment.

Vulvar Squamous Cell Carcinoma (VSCC) as Two Diseases: HPV Status Identifies Distinct Mutational Profiles Including Oncogenic Fibroblast Growth Factor Receptor 3.

Patients with advanced or recurrent invasive vulvar squamous cell carcinoma (VSCC) have limited treatment options and a grave prognosis. Understanding the genomic landscape may facilitate the identification of new therapies and improve clinical outcomes. A retrospective chart review and molecular analysis of patients with VSCC from 2000 to 2016 was performed at the Ottawa Hospital Research Institute.