Non-small-cell lung cancer articles within Nature Reviews Clinical Oncology

Featured

  • Review Article |

    The recognition of non-small-cell lung cancer (NSCLC) as a heterogeneous disease and ongoing efforts to characterize disease subtypes based on genotype and histology have resulted in dramatic improvements in outcomes for select patient subgroups. However, many challenges remain, not least acquired therapeutic resistance and the related issue of how to best use the available therapies. In this Review, the authors provide an overview of the key developments in NSCLC therapy, describe efforts to tackle therapeutic resistance, and discuss potential strategies to further optimize patient outcomes by stratifying treatments according to particular disease subtypes.

    • Anish Thomas
    • , Stephen V. Liu
    •  & Giuseppe Giaccone

  • Year in Review |

    In 2014, developments in our understanding of escape signalling circuits implicated in resistance to targeted agents in patients with lung cancer have led to improvements in tackling such resistance. The potential role for PET in the management of erlotinib therapy, novel combination therapies and pharmacogenomic-driven individualization of platinum-based chemotherapy represent other key advances.

    • Rafael Rosell
    •  & Niki Karachaliou

  • Review Article |

    The classical end points—overall survival, progression-free survival, and response rate—used in cancer clinical trials have important limitations that not only increase the cost and duration of the drug development process, but can also confound establishment of a statistically significant clinical benefit. This Review discusses these issues, and highlights the urgent need for biomarker-based end points, focusing on those that are under investigations in lung cancer, that closely correlate with disease outcomes and that, therefore, hold promise as surrogates for traditional clinical end points.

    • Joel W. Neal
    • , Justin F. Gainor
    •  & Alice T. Shaw

  • News & Views |

    With no large randomized phase III trials to provide definitive answers, the ideal number of platinum-based chemotherapy cycles in patients with advanced non-small-cell lung cancer has long been unclear. Most guidelines recommend a maximum of 4–6 cycles. Rossi and colleagues now suggest that four chemotherapy cycles is the optimal regimen.

    • Solange Peters
    •  & Alex A. Adjei

  • Research Highlight |

    • Lisa Hutchinson

  • Review Article |

    This Review explores breakthroughs in our understanding and treatment of acquired resistance to tyrosine kinase inhibitors in key molecular subtypes of non-small-cell lung cancer, which may be relevant across multiple different solid malignancies with oncogene-addicted subtypes. The potential of a number of clinical approaches to treat acquired resistance, from new drugs or drug combinations through to the use of more traditional therapies such as radiation or cytotoxic chemotherapy, are highlighted, and the implications for major changes in conducting clinical research in this setting are discussed.

    • D. Ross Camidge
    • , William Pao
    •  & Lecia V. Sequist

  • News & Views |

    Over the past three decades, the interpretation of clinical trial outcomes in studies of advanced-stage non-small-cell lung cancer has changed. The robustness of findings from these trials has been called into question. We believe this change is a reflection of the improved understanding of molecular-based therapeutics and continued advances in this field.

    • Herbert H. Loong
    •  & Tony S. K. Mok

  • Year in Review |

    In 2013, the treatment of several NSCLC subtypes was refined. PROFILE-1007 and LUX-Lung 3 confirmed that targeted therapy was superior to chemotherapy, whereas NCIC BR19 and PointBreak failed to show superiority of adjuvant gefitinib and combined maintenance therapy, respectively. These studies reinforced some practices and discouraged others, underscoring the need for new prospective studies.

    • Stephen V. Liu
    •  & Giuseppe Giaccone

  • Review Article |

    Advances in single-cell molecular analysis are enhancing our ability to explore the mechanisms of metastasis. In this Review, the authors describe how circulating tumour cells (CTCs), captured from a minimally invasive blood test—and readily amenable to serial sampling—have the potential to inform intratumour heterogeneity and tumour evolution.

    • Matthew G. Krebs
    • , Robert L. Metcalf
    •  & Caroline Dive

  • News & Views |

    Two phase III trials have shown that prolonging chemotherapy duration improves outcome in patients with nonsquamous non-small-cell lung cancer. Pemetrexed versus placebo, and pemetrexed–bevacizumab versus bevacizumab was tested in patients without disease progression after pemetrexed–cisplatin treatment. Biomarker-directed chemotherapy and/or targeted therapy could further improve treatment outcomes for patients with lung cancer.

    • Rafael Rosell
    •  & Niki Karachaliou

  • News & Views |

    On 15 July 2013, the FDA approved afatinib as a first-line treatment for patients with metastatic non-small-cell lung cancer whose tumours harbour exon 19 deletions or exon 21 (L858R) EGFR substitution mutations. We discuss three recent studies investigating afatinib in this molecular subset of patients.

    • Helena A. Yu
    •  & William Pao

  • News & Views |

    The standard treatment for patients with advanced-stage non-small-cell lung cancer with a performance status of 2 is unclear because of the heterogeneity of this population. Although a recent trial suggests that carboplatin plus pemetrexed improves survival as compared to single-agent pemetrexed, we should be cautious when defining new standards of treatment on the basis of single small trials.

    • Cesare Gridelli

  • News & Views |

    Rearrangements of the ALK gene have been associated with sensitivity to crizotinib and other kinase inhibitors with activity against ALK. The phase III PROFILE 1007 randomized study of crizotinib versus chemotherapy has demonstrated that crizotinib is superior to standard second-line chemotherapy in ALK-positive non-small-cell lung cancer.

    • Robert C. Doebele

  • Review Article |

    Advances in surgical oncology have improved patient safety and provided less-invasive procedures. In the era of personalized medicine, the value of surgical specimens for understanding tumour biology, extended indication of surgery, the role of surgical oncology in trials that examine neoadjuvant therapy in patients selected by appropriate biomarkers, and the possibilities to personalize the surgical procedure itself according to lung cancer subtypes are discussed.

    • Tetsuya Mitsudomi
    • , Kenichi Suda
    •  & Yasushi Yatabe

  • News & Views |

    The VELOUR and VITAL studies recently demonstrated ziv-aflibercept improved overall survival in patients with metastatic colorectal cancer (mCRC), including those previously treated with bevacizumab, but did not improve overall survival in non-small-cell lung cancer. Thus, VEGF-directed agents might be useful throughout the continuum of care in mCRC, but biomarkers are needed to identify patients likely to benefit.

    • Jeffrey M. Clarke
    •  & Herbert I. Hurwitz

  • Perspectives |

    Many patients who present with stage III NSCLC are in their 70s with multiple comorbidities who are generally unfit to receive the standard chemoradiotherapy regimen. In this Perspectives article, the author puts forth proposals to advance research within shorter timescales to improve outcomes for patients for whom standard treatment is unavailable.

    • Allan Price

  • News & Views |

    Treatment of locally advanced non-small-cell lung cancer (NSCLC) in the elderly is challenging, with many available treatment options from radiotherapy alone to sequential chemoradiation. The latest phase III trial comparing radiotherapy alone with concurrent chemoradiation reported a survival improvement for the combination; however, this does not define a new standard treatment.

    • Cesare Gridelli

  • Review Article |

    Crizotinib has provided dramatic and prolonged benefit for patients with the ALK-positive subtype of non-small-cell lung cancer. Despite these early successes, many challenges remain including understanding the mechanisms of resistance to crizotinib. This Review examines what we already know and the major emerging questions associated with optimal management of this disease.

    • D. Ross Camidge
    •  & Robert C. Doebele

  • Review Article |

    DNA repair as a therapeutic target has received considerable attention in the treatment of non-small-cell lung cancer (NSCLC). In this Review, Postel-Vinay et al. discuss how optimizing treatment of NSCLC according to DNA-repair biomarkers, such as ERCC1, BRCA1 or RRM1, may aid clinical decision making and improve the outcome of patients with NSCLC.

    • Sophie Postel-Vinay
    • , Elsa Vanhecke
    •  & Jean-Charles Soria

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