Research Highlight |
Featured
-
-
Review Article |
Comparing and contrasting predictive biomarkers for immunotherapy and targeted therapy of NSCLC
The advent of effective molecularly targeted treatments and immunotherapies for non-small-cell lung cancer (NSCLC) has greatly improved patient outcomes. Whereas most patients selected for treatment with molecularly targeted drugs derive benefits from these agents, benefit from immunotherapy is more difficult to predict. Herein, Camidge and colleagues compare and contrast predictive biomarkers for immunotherapy and targeted therapy of NSCLC to highlight considerations for biomarker development.
- D. Ross Camidge
- , Robert C. Doebele
- & Keith M. Kerr
-
Year in Review |
A banner year for immunotherapy and targeted therapy
In 2018, advances in the treatment of non-small-cell lung cancer (NSCLC) have been observed both in trials of immunotherapies and targeted agents, leading to dramatically improved options for patients with metastatic and stage III NSCLC.
- Jennifer W. Carlisle
- & Suresh S. Ramalingam
-
-
-
-
-
-
Review Article |
Making the first move in EGFR-driven or ALK-driven NSCLC: first-generation or next-generation TKI?
The clinical management of patients with non-small-cell lung carcinoma has greatly evolved owing to the development of tyrosine-kinase inhibitors (TKIs) targeted against the driver mutations of this disease. The authors of this Review describe the existing evidence on the sequential administration of TKIs and the use of next-generation TKIs upfront.
- Gonzalo Recondo
- , Francesco Facchinetti
- & Luc Friboulet
-
News & Views |
Frontline immunotherapy for NSCLC: alone or not alone?
Platinum-based chemotherapy has long been the mainstay first-line therapy for patients with non-small-cell lung cancer without a targetable driver mutation, but has limited effectiveness. Immunotherapy is drastically changing the treatment landscape for this group and improving survival outcomes, with focus turning to frontline immunotherapy combinations.
- Cesare Gridelli
- & Francesca Casaluce
-
-
Perspective |
Early stage NSCLC — challenges to implementing ctDNA-based screening and MRD detection
Liquid biopsy approaches hold great promise in early cancer diagnosis or minimal residual disease monitoring for cancer recurrence. Herein, the authors evaluate contemporary next-generation sequencing approaches to circulating tumour DNA detection in these contexts, with a focus on studies in patients with non-small-cell lung cancer. They discuss the feasibility of introducing these strategies into the clinic, highlighting the technical and analytical challenges, as well as possible solutions.
- Christopher Abbosh
- , Nicolai J. Birkbak
- & Charles Swanton
-
-
-
-
-
-
News & Views |
Precision oncology in non-small-cell lung cancer: opportunities and challenges
Major advances in our understanding of the molecular pathogenesis of non-small-cell lung cancer (NSCLC) have led to effective targeted therapeutics in several genomically-defined subsets of NSCLC. The recently updated College of American Pathologists, International Association for the Study of Lung cancer, and Association for Molecular Pathology joint guideline, which was endorsed by ASCO, sets new standards for molecular testing in NSCLC.
- Chul Kim
- & Giuseppe Giaccone
-
-
News & Views |
Immune-modified response criteria — an iterative learning process?
Patients with solid tumours can have unusual patterns of response to anticancer immunotherapy, necessitating the adaptation of traditional response criteria. A recent retrospective analysis of data from patients with four different types of solid tumours treated with the anti-programmed cell death 1 ligand 1 (PD-L1) antibody atezolizumab confirms the previous experience in patients with melanoma and provides several new insights.
- Patrick A. Ott
-
-
-
-
Year in Review |
Giant steps and stumbling blocks
In 2017, major advances in the treatment of non-small-cell lung cancer (NSCLC) continued to emanate from the fields of molecularly targeted therapy and immunotherapy. In the former, new drugs with improved efficacy and reduced toxicity entered the clinic; in the latter, immune-checkpoint inhibition proved efficacious after chemoradiotherapy for stage III disease, but had disparate results in the frontline treatment of stage IV disease.
- David F. Heigener
- & Martin Reck
-
Review Article |
Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes
The receptor-tyrosine kinase RET has been identified as a potentially actionable driver of oncogenesis. Several multikinase inhibitors with activity against RET have been explored in the clinic, but have only modest efficacy in patients with thyroid cancers, mostly in those withRET mutations, or RET-rearranged lung cancers. Herein, the authors outline the aberrations in RET that contribute to tumorigenesis, review the current clinical data for inhibitors of this kinase, and discuss whether the limited clinical success achieved with these agents to date is attributable to the intractability of RET as a drug target or the lack of highly specific RET inhibitors.
- Alexander Drilon
- , Zishuo I. Hu
- & Daniel S. W. Tan
-
Review Article |
Tumour heterogeneity and resistance to cancer therapies
The onset of acquired resistance to treatment is virtually inevitable in patients with solid tumours. In this Review, the authors describe the role of tumour heterogeneity in the development of acquired resistance, potential treatment strategies that take into account the heterogeneity of patient's tumours, and how a better understanding of tumour heterogeneity might improve the outcomes of patients.
- Ibiayi Dagogo-Jack
- & Alice T. Shaw
-
-
-
-
-
-
-
-
-
-
-
-
-
News & Views |
Best supportive care — a reasonable option for patients with brain metastases?
Most patients with cancer who develop brain metastases have a very poor prognosis, especially those with brain metastases from non-small-cell lung cancer. The short life-expectancy of these patients, which is typically measured in weeks or a few months, raises an important question: do they benefit from whole-brain radiotherapy, or are they appropriately treated with best supportive care alone? A recent randomized trial sought to answer this question.
- Dirk Rades
- & Steven E. Schild
-
-
-
News & Views |
Stage III NSCLC — is it time to centralize care?
Eaton et al. report a very strong association between institutional clinical trial accrual volume and the survival of patients with stage III NSCLC. The observed volume effect might have been exaggerated by artefact. More work is required to quantify the volume effect and understand its causes, before rushing to centralize care.
- William J. Mackillop
- & Christopher M. Booth
-
News & Views |
First-line immunotherapy in lung cancer — taking the first step
The use of programmed cell-death protein 1 (PD-1) inhibitors has become the standard-of-care approach for patients with advanced-stage, previously treated non-small-cell lung cancer. The inevitable adoption of these agents in the first-line setting is rapidly approaching, but the optimal strategy remains unclear. Two published clinical trial reports, examining different approaches, help to frame this question.
- Stephen V. Liu
- & Giuseppe Giaccone
-
News & Views |
Using ctDNA to track EGFR and KRAS mutations in advanced-stage disease
Analysis of circulating tumour DNA (ctDNA) in blood samples provides a surrogate form of tumour biopsy (liquid biopsy) for determining EGFR and KRAS mutation status in patients with advanced-stage non-small-cell lung cancer. This approach obviates the need for a repeat biopsy, especially for the EGFR T790M mutation, which confers resistance to EGFR inhibition.
- Rafael Rosell
- & Niki Karachaliou
-
-
-
-
Year in Review |
Immune-checkpoint blockade — durable cancer control
In 2015, advances in immunotherapy for metastatic melanoma have come to fruition, with phase III data supporting the combination of ipilimumab and nivolumab as first-line therapy. Understanding the mechanisms involved in an effective antitumour immune response are now key to further advances. Several studies published in 2015 have increased our understanding of the complex relationships that exist between our immune system and malignancy.
- Elizabeth I. Buchbinder
- & F. Stephen Hodi
-
News & Views |
Adjuvant TKIs in NSCLC: what can we learn from RADIANT?
In the RADIANT study, no difference in disease-free survival was observed for patients with non-small-cell lung cancer (NSCLC) treated with erlotinib versus placebo in the adjuvant setting. Further biomarker studies are awaited to determine whether patients with NSCLC can benefit from adjuvant therapy with tyrosine kinase inhibitors.
- Fred R. Hirsch
- & Paul A. Bunn Jr
-
Sequencing cells of the immune TME
Nivolumab–ipilimumab — exploiting the mutation burden of NSCLCs
Moving on up — from stage IV into stage III
Defining the best-in-class in NSCLC
KEYNOTE-001 — combo improves melody
Tracing tumour evolution
AURA3 magic reveals new standard
Benefit with anti-PD-L1
Anti-PD-1 therapy in the frontline
Clonal neoantigens and immune response: a balancing act
Resolving resistance to ALK-targeted therapy