Introduction: Liquid biopsy is recommended to diagnose molecular resistance to targeted therapy in patients with lung cancer. Nevertheless, not all jurisdictions provide funding and patient access. We report patients' perceived value of liquid biopsy in targeted therapy resistance.
View Article and Find Full Text PDFIntroduction: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trials; however, their efficacy in the real-world setting is unknown.
Methods: A retrospective efficacy and safety analysis was performed on data from RET fusion-positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021.
Introduction: MEK inhibition is a potential therapeutic strategy in non-small cell lung cancer (NSCLC). This phase I study evaluates the MEK inhibitor binimetinib plus carboplatin and pemetrexed in stage IV non-squamous NSCLC patients (NCT02185690).
Methods: A standard 3 + 3 dose-escalation design was used.
Purpose: Plasma detection of T790M mutations is an emerging alternative to tumor rebiopsy in acquired epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance. Validation of analytical sensitivity and clinical utility is required before routine diagnostic use in clinical laboratories.
Patients And Methods: Sixty-three patients with advanced -mutant lung cancer at 7 Canadian centers, who were being screened for the ASTRIS trial (ClinicalTrials.
Purpose: Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) demonstrated survival benefit versus bevacizumab, carboplatin, and paclitaxel (BCP) in chemotherapy-naïve nonsquamous non-small-cell lung cancer (NSCLC). We present safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in nonsquamous NSCLC.
Methods: Patients were randomly assigned to receive atezolizumab, carboplatin, and paclitaxel (ACP), ABCP, or BCP.
Background: Little evidence has been generated for how best to manage patients with non-small-cell lung cancer (nsclc) presenting with rarer clinical scenarios, including oligometastases, oligoprogression, and pseudoprogression. In each of those scenarios, oncologists have to consider how best to balance efficacy with quality of life, while maximizing the duration of each line of therapy and ensuring that patients are still eligible for later options, including clinical trial enrolment.
Methods: An expert panel was convened to define the clinical questions.
For more than a decade, there has been no improvement in outcomes for patients with unresectable locally advanced (la) non-small-cell lung cancer (nsclc). The standard treatment in that setting is definitive concurrent chemotherapy and radiation (ccrt). Although the intent of treatment is curative, most patients rapidly progress, and their prognosis is poor, with a 5-year overall survival (os) rate in the 15%-25% range.
View Article and Find Full Text PDFBackground: Nivolumab was the first immuno-oncology agent available for the treatment of lung cancer in Canada. In the present study, we evaluated the real-world benefit of nivolumab in Canadian patients with lung cancer.
Methods: Patients included in the cohort were identified from a registry of patients treated through expanded access to nivolumab before and after Health Canada approval.
The treatment of advanced non-small-cell lung cancer (nsclc) has undergone a paradigm shift since the early 2000s. The identification of molecular subtypes of the disease, based on oncogenic drivers, has led to the development of personalized medicine and the ability to deliver molecularly targeted therapies to patients. In the 10 years that have elapsed since the discovery of the gene in a patient with nsclc, several active drugs have moved rapidly from bench to bedside, and multiple others are currently in clinical trials.
View Article and Find Full Text PDFObjectives: 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.
Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non-small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC). Patients and Methods Eligible patients had advanced-stage NSCLC, no CNS metastases, and zero to two or more lines of prior chemotherapy.
View Article and Find Full Text PDFBackground: Crizotinib was the first agent approved for the treatment of anaplastic lymphoma kinase ()-positive (+) non-small-cell lung cancer (nsclc), followed by ceritinib. However, patients eventually progress or develop resistance to crizotinib. With limited real-world data available, the objective of the present work was to evaluate treatment patterns and survival after crizotinib in patients with locally advanced or metastatic + nsclc in Canada.
View Article and Find Full Text PDFBackground: Icrucumab and ramucirumab are recombinant human IgG1 monoclonal antibodies that bind VEGF receptors 1 and 2 (VEGFR-1 and -2), respectively. This randomized phase II study evaluated the antitumor activity and safety of icrucumab and ramucirumab each in combination with mFOLFOX-6 in patients with metastatic colorectal cancer after disease progression on first-line therapy with a fluoropyrimidine and irinotecan.
Patients And Methods: Eligible patients were randomly assigned to receive mFOLFOX-6 alone (mFOLFOX-6) or in combination with ramucirumab 8 mg/kg IV (RAM+mFOLFOX-6) or icrucumab 15 mg/kg IV (ICR+mFOLFOX-6) every 2 weeks.
Targeting the epidermal growth factor receptor (egfr) pathway has become standard practice for the treatment of advanced non-small-cell lung cancer. Compared with chemotherapy, egfr tyrosine kinase inhibitors (tkis) have been associated with improved efficacy in patients with an EGFR mutation. Together with the increase in efficacy comes an adverse event (ae) profile different from that of chemotherapy.
View Article and Find Full Text PDFAnaplastic lymphoma kinase (ALK) rearrangements have been identified as key oncogenic drivers in a small subset of non-small-cell lung cancers (nsclcs). Small-molecule Alk kinase inhibitors such as crizotinib have transformed the natural history of nsclc for this subgroup of patients. Because of the prevalence of nsclc, ALK-positive patients represent an important example of the paradigm for personalized medicine.
View Article and Find Full Text PDFBackground: Phase III clinical trials and Food and Drug Administration (FDA) regulatory decisions are critical for success of new drugs and can influence a company's market valuation. Knowledge of trial results before they are made public (ie, "inside information") can affect the price of a drug company's stock. We examined the stock prices of companies before and after public announcements regarding experimental anticancer drugs owned by the companies.
View Article and Find Full Text PDFObjectives: Neuroendocrine tumors (NETs) are uncommon malignancies with variable natural history and often indolent biological behavior. Over the past decade, novel treatment approaches have been developed. The purpose of this study was to review the experience at the Princess Margaret Hospital in treating patients with NET over the past decade.
View Article and Find Full Text PDFBackground: Road traffic injury is the leading cause of death among Canadian children and youth. Transport Canada recommends four types of child restraint depending on the size of the child, and recent studies have demonstrated the effectiveness of recommended restraint use.
Objectives: To determine community paediatricians' knowledge of Transport Canada recommendations for child restraint use in vehicles, and to examine paediatricians' counseling patterns in relation to child passenger safety.
TGF-beta is a multifunctional factor involved in regulating a variety of cellular activities. In mammals, TGF-beta is known to regulate reproduction, including ovarian functions. The role of TGF-beta in lower vertebrates, such as fish, is poorly understood.
View Article and Find Full Text PDFTransforming growth factor beta (TGF-beta) induces G(1) arrest in susceptible cells by multiple mechanisms that inhibit the G(1) cyclin-dependent kinases (Cdks), including Cdk2, Cdk4, and Cdk6. TGF-beta treatment of early passage finite lifespan human mammary epithelial cells (HMECs) led to an accumulation of p27(Kip1) in cyclin E1-Cdk2 complexes and kinase inhibition. The requirement for p27 in the G(1) arrest by TGF-beta was assessed by transfection of antisense p27 (ASp27) oligonucleotides into TGF-beta-treated HMECs.
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