Clinical Outcomes With Dabrafenib Plus Trametinib in a Clinical Trial Versus Real-World Standard of Care in Patients With BRAF-Mutated Advanced NSCLC

INTRODUCTION: BRAF mutations are rare in patients with NSCLC, and treatment options are limited. Dabrafenib plus trametinib (dab-tram) was approved for BRAF(V600)-mutated advanced NSCLC (aNSCLC), based on results from a phase 2 study (NCT01336634). This retrospective analysis compared the effectiveness of dab-tram, based on previously reported clinical trial data, versus real-world standard of care in patients with BRAF-mutated aNSCLC. METHODS: Real-world cohorts were derived from a deidentified real-world database (2011–2020) and included patients with BRAF-mutated aNSCLC receiving first-line platinum-based chemotherapy (PBC), first-line immune checkpoint inhibitors (ICIs) plus PBC, or second-line ICIs. Weighting by odds was used to estimate the average treatment effect of the treated. RESULTS: For first-line dab-tram versus PBC, the hazard ratio (HR; 95% confidence interval) for death in unweighted and weighted analyses was 0.65 (0.39–1.1) and 0.51 (0.29–0.92; p = 0.03), respectively; unweighted and weighted median overall survival was 17.3 (12.3–40.2) versus 14.5 (9.2–19.6) months and 17.3 (14.6-not reached) versus 9.7 (6.4–19.6) months, respectively. Hazard ratio of death in unweighted and weighted analyses was 0.56 (0.29–1.1) and 0.57 (0.28–1.17), respectively, with first-line dab-tram versus PBC plus ICI, and 0.65 (0.39–1.07) and not reported (Cox proportional-hazards assumption violated), respectively, with second-line dab-tram versus ICI. CONCLUSIONS: In this indirect comparison in patients with BRAF-mutated aNSCLC, the risk of death was lower and median overall survival was longer with first-line dab-tram versus PBC. In analyses of dab-tram versus first-line PBC plus ICI or second-line ICI, sample sizes were small and findings were inconclusive with overlapping confidence intervals. Despite some limitations, the study provides useful data for this rare patient population

Correlations of EGFR mutations and increases in EGFR and HER2 copy number to gefitinib response in a retrospective analysis of lung cancer patients

<p>Abstract</p> <p>Background</p> <p>Gefitinib, a small molecule tyrosine kinase inhibitor of the Epidermal Growth Factor Receptor (<it>EGFR</it>), has shown limited efficacy in the treatment of lung cancer. Recognized clinical predictors of response to this drug, specifically female, non-smoker, Asian descent, and adenocarcinoma, together suggest a genetic basis for drug response. Recent studies have addressed the relationship between response and either sequence mutations or increased copy number of specific receptor tyrosine kinases. We set out to examine the relationship between response and the molecular status of two such kinases, <it>EGFR </it>and <it>HER2</it>, in 39 patients treated with gefitinib at the BC Cancer Agency.</p> <p>Methods</p> <p>Archival patient material was reviewed by a pathologist and malignant cells were selectively isolated by laser microdissection or manual recovery of cells from microscope slides. Genomic DNA was extracted from 37 such patient samples and exons 18–24, coding for the tyrosine kinase domain of <it>EGFR</it>, were amplified by PCR and sequenced. <it>EGFR </it>and <it>HER2 </it>copy number status were also assessed using FISH in 26 samples. Correlations between molecular features and drug response were assessed using the two-sided Fisher's exact test.</p> <p>Results</p> <p>Mutations previously correlated with response were detected in five tumours, four with exon 19 deletions and one with an exon 21 missense L858R point mutation. Increased gene copy number was observed in thirteen tumours, seven with <it>EGFR </it>amplification, three with <it>HER2 </it>amplification, and three with amplification of both genes. In our study cohort, a correlation was not observed between response and <it>EGFR </it>mutations (exon 19 deletion p = 0.0889, we observed a single exon 21 mutation in a non-responder) or increases in <it>EGFR </it>or <it>HER2 </it>copy number (p = 0.552 and 0.437, respectively).</p> <p>Conclusion</p> <p>Neither mutation of <it>EGFR </it>nor increased copy number of <it>EGFR </it>or <it>HER2 </it>was diagnostic of response to gefitinib in this cohort. However, validation of these features in a larger sample set is appropriate. Identification of additional predictive biomarkers beyond <it>EGFR </it>status may be necessary to accurately predict treatment outcome.</p

Low Grade Neuroendocrine Tumors of the Lung

The lung is the second most common site of neuroendocrine tumors (NETs). Typical and atypical carcinoids are low-grade NETs of the lung. They present a favorable prognosis comported to the more common high-grade NETs. The low- and high-grade NETs require different treatment strategies; effective management of these tumors is essential to prolong survival and to manage the symptoms in patients with secretory or functional tumors. These rare tumors have received little attention and education is needed for treating physicians. This mini-review will concentrate mainly on advanced low-grade lung NETs. The article describes the classification of lung NETs and the diagnostic work-up. Different treatment methods including somatostatin analogs, peptide receptor radioligand therapy, and biologic systemic therapy are discussed. Promising results from recent trials are presented and discussed in the context of the lung primary site

Meeting An Unmet Need in Metastatic Colorectal Carcinoma with Regorafenib

Colorectal cancer is a global issue, affecting men and women equally. Over the last 25 years, advances in therapy and multidisciplinary care have led to improvements in survival for those with colorectal cancer. Despite these advances, more therapeutic options are needed for those being treated for this disease.Regorafenib is an oral drug that is a new therapeutic option for our patients. The CORRECT and CONCUR trials demonstrate the efficacy of regorafenib in the last line setting. This article summarizes some of the regorafenib clinical trial data and discusses the strategies to help manage the side effects of this drug including patient education, dose reductions and interruptions, and monitoring hypertension and liver function

Immunotherapy in Thoracic Malignancies: New Treatment and New Hope

Over these last two pandemic years, we have all experienced profound changes in how we practice, how we work, and how we live [...

The Treatment of Metastatic Non-small Cell Lung Cancer (NSCLC) in New Era of Personalised Medicine

Lung cancer is the leading cause of cancer related mortality in Canada and USA. Majority of the patients present in advanced stage of the disease and of these only about 2% will be alive at 5 years. NSCLC is the most common form of lung cancer, accounting for approximately 87% of cases. Systemic chemotherapies have been used to treat metastatic NSCLC for decades, but the improvements of outcomes have reached a plateau. Recent advances in understanding signalling pathways for malignant cells, their interconections,the importance of various receptors and biomarkers and the interplay between various oncogenes have led to the development of targeted treatments that are improving both efficacy and safety of the treatments. Knowledge about the advantages of treatments with the targeted agents in metastatic NSCLC is growing rapidly. Combining various targeted agents or sequencing them properly will be important in the era of personalised medicine and overcoming development of the resistence to various targeted agents will be challenging. The importance of a team work,from the diagnosis through various treatments, to supportive care, from the interventional radiologists, pneumologists or surgeons, who have to obtain a satisfactory tumor tissue specimen, to pathologists, radiation and medical oncologists, to supportive care specialists, will be described in our publications. We will cover completely present and future approaches to personalised medicine in this rapidly evolving field of metastatic NSCLC

Update on the Treatment of Metastatic Non-small Cell Lung Cancer (NSCLC) in New Era of Personalised Medicine

Lung Cancer remains a major cause of death in of both women and men in our society. Lung cancer treatment paradigms have changed enormously as we’ve started to understand the genetic complexity and the multiple driver mutations influencing the disease. Therapeutics directed towards, or to inhibit signaling pathways has resulted in increased life spans for our patients. Over the last two decades, we have gone from simple chemotherapy used to treat all, to a personalized medicine approach for the majority. For non-small cell lung cancer patients without driver mutations, the world of immune oncology has arrived. These improved long-term outcomes mean that now our lung cancer patients can live with their cancers, but without progression. The aim of this book is to catalogue the current state of knowledge for the many facets of advanced lung cancer. It describes current treatment approaches for driver mutations, rare mutations, and rare thoracic malignancies such as neuroendocrine tumors. Most importantly, this book addresses the topics of palliative treatment and care which allow our patients to enjoy longer survival with the highest quality of life. We hope you enjoy this e-book. The future is brighter for lung cancer patients and as lung cancer specialists; we finally feel sense optimism about treatment options for our patients

Immunotherapy in the First-Line Setting in Wild-Type NSCLC

Treatment algorithms in the treatment of advanced non-small cell lung cancer (NSCLC) continue to evolve as new therapeutics show positive efficacy improvements. This review article summarizes the data for the use of immunotherapy for treatment in first-line stage IV NSCLC, organized by the following four sections: single-agent immunotherapy, immunotherapy and chemotherapy, dual immunotherapy, and dual immunotherapy and chemotherapy. The results are summarized and tabulated. Finally, application of the trial data is illustrated in four clinical scenarios depending on the programmed death-ligand 1 (PD-L1) expression levels. Single checkpoint inhibitors have become an easy and excellent treatment in patients whose tumors have high PD-L1 expression. Adding chemotherapy to immunotherapy benefits our patients. Immunotherapy, with or without chemotherapy, is now the standard of care in the first-line setting in patients without EGFR, ALK, or ROS driver mutations