Comment

  • Comment |

    Breast oncologists are intimately familiar with managing treatment-related adverse events of endocrine, cytotoxic and targeted therapies, but the approval of immune-checkpoint inhibitors (ICIs) for metastatic triple-negative breast cancer (TNBC) poses new challenges. Herein, we discuss the safety of ICIs in metastatic TNBC, with an emphasis on immune-related adverse events.

    • Nina D’Abreo
    •  & Sylvia Adams
  • Comment |

    The approval of therapeutic agents that are tested in patients deemed ineligible for intensive or aggressive therapy is increasingly popular. This approach enables comparisons of novel therapies with less-aggressive agents, as well as data from nonrandomized studies to be used for market authorization. Herein, we discuss three mechanisms that could be adopted to avoid the temptation of applying this strategy excessively.

    • Rachel J. Cook
    • , Jennifer Gill
    •  & Vinay Prasad
  • Comment |

    In 2018, the FDA approved 19 new drug and biologic applications, 38 supplemental drug and biologic applications and 4 biosimilar applications in oncology. These advances in anticancer therapy included a landmark approval of the first histology-agnostic, biomarker-defined new molecular entity and approvals based on real-time data review and novel end points, such as minimal residual disease rate and metastasis-free survival.

    • Gideon M. Blumenthal
    •  & Richard Pazdur
  • Comment |

    Multidisciplinary team meetings have several flaws; herein, we propose approaches for cancer centres to transform these limitations into improvements in the quality control of oncological care and into research opportunities.

    • N. Gopalakrishna Iyer
    •  & Melvin L. K. Chua
  • Comment |

    The value of medical treatments is an issue that has been actively debated in recent years and is not unique to oncology. In this Comment, we discuss why we pursue treatments which might have limited benefit from the point of view of three parties: the patient, the physician, and the pharmaceutical industry.

    • Christopher M. Booth
    •  & Allan S. Detsky
  • Comment |

    Burnout is a substantial issue associated with the medical profession, with oncology being no exception. Increasing focus is being placed on implementing solutions to address physician burnout, and successful interventions have encompassed the following themes: the presence of an organizational mandate, data-driven and grassroots quality improvements, and a focus on systems change.

    • Krithika Murali
    •  & Susana Banerjee
  • Comment |

    Immune-checkpoint inhibitors (ICIs) are transforming oncology, but the mounting costs of cancer care necessitate concerns regarding economic sustainability. Here, several strategies that clinicians could use to exercise economically prudent administration of ICIs are discussed. These include better appraisal of the cost-effectiveness literature, judicious patient selection, separating statistical from clinical significance, and careful patient counselling.

    • Vivek Verma
  • Comment |

    Drug regulators’ acceptance of any statistically significant improvement shown in a single randomized trial and lofty drug prices has created a situation where it is now, hypothetically, profitable for a company to run a clinical trials portfolio of chemically inert compounds. While the current cancer drug pipeline is certainly superior to inert drugs, we must rethink market incentives to encourage transformational drug development.

    • Vinay Prasad
    • , Christopher McCabe
    •  & Sham Mailankody
  • Comment |

    According to the paradigm of precision medicine, the administration of agents targeting the molecular alteration detected in a particular patient’s tumour reduces uncertainty in the clinical management of that patient. We describe how approaches to precision medicine can lead, paradoxically, to increased levels of uncertainty. We offer recommendations for how physicians can better navigate new uncertainties in precision medicine.

    • Jonathan Kimmelman
    •  & Ian Tannock
  • Comment |

    Experimental research on cancer-associated cachexia is advancing at an accelerated pace while knowledge of the complex underlying biology of cachexia in humans lags behind. An unmet need exists to accelerate the identification of causal mechanisms in patients with cancer and to determine the parallels between experimental systems and distinct isotypes of human cachexia.

    • Vickie E. Baracos
  • Comment |

    In 2017, FDA Oncology approved 17 new drug and biologic applications, 32 supplemental drug and biologic applications, and two biosimilar applications in oncology. These actions included landmark approvals of two chimeric antigen receptor T cell therapies and the first site-agnostic, biomarker-defined approval. Three next-generation sequencing 'oncopanels' designed to detect hundreds of somatic genetic aberrations were also approved.

    • Gideon M. Blumenthal
    •  & Richard Pazdur
  • Comment |

    A call for action has been made for the establishment of a global fund for cancer control, but potential donors have not reacted yet, possibly because this task would require an annual expenditure of billions of dollars. Herein, I suggest a less onerous starting point: targeting childhood cancer in Africa guided by well-designed national cancer control plans.

    • Cristina Stefan
  • Comment |

    We posit that disseminating tumour cells detected in the bone marrow or in the circulation are either cancer stem cells with full metastatic potential, tumour-bulk cells, or dormant cancer cells. This model has both therapeutic and diagnostic implications, raising concern over inadequate treatment as well as the possibility of overtreatment resulting from overdiagnosis.

    • Klaus Pantel
    •  & Daniel F. Hayes
  • Comment |

    Women's health is more than reproductive health. Why does this phrase still need to be repeated? This commentary highlights the urgent need to encourage more women to lead, research, and educate to move beyond stereotypes and to ensure we push forward in improving the lives of women everywhere.

    • Ophira Ginsburg
  • Comment |

    Few clinical trials incorporate studies of evolutionary cancer biology, despite the frequent emergence of acquired resistance to anticancer therapies. This problem motivated the first CRUK Marshall Symposium on Cancer Evolution in May 2017, which provided a forum for evolutionary and ecological theorists, cancer biologists, and clinicians to consider how evolutionary biology might inform improvements in cancer medicine. Herein, we discuss the key themes and opportunities for the future.

    • Erik Sahai
    • , Charles Swanton
    •  & and Marshall Symposium
  • Comment |

    Scientific Advice meetings are a mechanism to improve communications between drug developers and regulators during the drug-development process. While standard practice for industry, the benefits provided by these meetings are under-utilised by academia. In the context of drug repurposing, can scientific advice, as part of a proposed new R&D tax credits scheme, help to unblock some of the obstacles in the way to clinical adoption?

    • Pan Pantziarka
  • Comment |

    In studies investigating the combination of two or more anticancer drugs that are already approved for independent use, or 'maintenance' regimens, the use of progression-free survival as the end point for approval is inadequate; sequential treatment with the same agents or existing salvage therapies, respectively, might provide an equivalent survival benefit, with lower toxicity, cost, and treatment burden, therefore, the use of an overall survival end point is essential to justify such interventions.

    • Bishal Gyawali
    •  & Vinay Prasad
  • Comment |

    Patients with resectable solid tumours can harbour minimal residual disease (MRD) after initial treatment, which is a potential source for subsequent metastatic relapse. The interaction between disseminated tumour cells (DTCs) and the new microenvironment in which they reside determines whether DTCs remain dormant or progress into overt metastases. We highlight the promise of liquid biopsies to inform on MRD.

    • Klaus Pantel
    •  & Catherine Alix-Panabières
  • Comment |

    Does a patient with advanced incurable disease have a right not to hear the bad news? We think not. Failing to disclose a poor prognosis undermines patient autonomy and increases the likelihood of poor end-of-life care.

    • Devan Stahl
    •  & Tom Tomlinson
  • Comment |

    Over the past decade, many anticancer drugs have been approved for use only in combination regimens and only in palliative settings, despite having negligible single-agent activity in the same disease. We examine whether these agents provide any tangible clinical benefits and are worthy of continued development, or whether R&D efforts would be better focused elsewhere.

    • Bishal Gyawali
    •  & Vinay Prasad
  • Comment |

    The 69 National Cancer Institute-designated Cancer Centers are premier academic institutions that place significant value on research integrity and an ethic that rigorous evidence should guide patient care and define expectations. Recent patient-focused advertising has strayed from these values, obscuring valid reasons for seeking care at these centres.

    • David Rubenson
    •  & Daniel S. Kapp
  • Comment |

    In 2016, FDA Oncology approved five new molecular entities and 17 efficacy supplements, including six accelerated approvals, 17 priority reviews, and 11 approvals of breakthrough-designated therapies. The FDA also approved five companion diagnostics, including a liquid biopsy test. One new anti-PD-L1 antibody was approved, along with six supplementary approvals of anti-PD-1/PD-L1 antibodies.

    • Gideon M. Blumenthal
    •  & Richard Pazdur
  • Comment |

    In 2016, four new anticancer drugs were approved by the FDA, and a further 12 existing agents were approved for 14 additional indications. Each one of these drugs is associated with important clinical benefits, but at an average monthly cost of US$9,000. Here, I discuss the cost–benefit considerations related to these treatments and contemplate future economic prospects.

    • Philip Savage
  • Comment |

    Patients with cancer expect to derive a meaningful clinical benefit from anticancer treatments, especially considering that such therapies are associated with adverse events and, often, substantial financial costs. We have evaluated new anticancer agents approved by the FDA in 2015 and 2016 using the ESMO Magnitude of Clinical Benefit Scale and ASCO Value Framework, and conclude that many agents only offer marginal value.

    • Christopher M. Booth
    •  & Joseph C. Del Paggio