Comment

Filters

  • Comment |

    The coronavirus disease 2019 (COVID-19) pandemic has disrupted health care worldwide. Patients with cancer seem to be particularly susceptible to morbidities and mortality from this novel disease. No COVID-19-specific therapy currently seems to offer a survival benefit to this unique patient population. Furthermore, the global effects on routine cancer care will likely be felt for decades to come.

    • Leora Horn
    •  & Marina Garassino
  • Comment |

    Single-arm phase II trials can provide compelling results that facilitate the approval of a new therapy. Designing and interpreting single-arm studies based on four principles — instinct, comparative analysis, statistical soundness and like-for-like comparisons — can provide indications as to which drugs are most likely to provide improved therapeutic options for patients.

    • Robert H. Glassman
    • , Grace Kim
    •  & Marc J. Kahn
  • Comment |

    Zanubrutinib was recently granted expedited approval by the USA and Chinese drug regulatory authorities for the treatment of mantle cell lymphoma, thus becoming the first investigational new drug discovered in China to achieve simultaneous development in both countries. Here, we provide an overview of the regulatory processes and considerations of the two health authorities and discuss the pathways of concurrent review and approval.

    • Guanqiao Li
    • , Xiaozhen Liu
    •  & Xiaoyuan Chen
  • Comment |

    Early published data on COVID-19 in patients with cancer are being referenced in clinical guidelines, despite methodological flaws that limit the quality of much of this evidence. In the next phase of research in this area, we argue that the quality of observational evidence should be prioritized over speed of publication.

    • Andrew G. Robinson
    • , Bishal Gyawali
    •  & Gerald Evans
  • Comment |

    The coronavirus disease 19 (COVID-19) pandemic has become the focus of attention worldwide, and herein we seek to highlight the potential problem of ‘collateral mortality’ from delayed or deferred treatments in patients with cancer. We propose potential solutions to ensure continuity of care in the field of surgical oncology.

    • Ker-Kan Tan
    • , Brendan J. Moran
    •  & Michael J. Solomon
  • Comment |

    Radiotherapy can be safely delivered during the coronavirus disease 2019 (COVID-19) pandemic, often through use of hypofractionated regimens, which minimize the number of visits to treatment centres while also avoiding potentially detrimental delays in the delivery of cancer care.

    • Himanshu Nagar
    •  & Silvia C. Formenti
  • Comment |

    Health-care services are rapidly transforming their organization and workforce in response to the coronavirus disease 2019 (COVID-19) pandemic. These changes, and a desire to mitigate infection risk, are having profound effects on other vital aspects of care, including the care of patients with cancer. Difficult decisions are being made regarding the prioritization of both active treatments and palliative care, despite limited evidence that cancer is an independent risk factor for infection and mortality.

    • James Spicer
    • , Charlotte Chamberlain
    •  & Sophie Papa
  • Comment |

    Informative censoring occurs when progression-free survival is the primary end point of a randomized clinical trial and unequal patient dropout is observed between treatment arms owing to poorer tolerance of experimental treatment. Herein we discuss how informative censoring in the experimental arm before criteria for disease progression are met causes bias towards a positive result.

    • Arnoud J. Templeton
    • , Eitan Amir
    •  & Ian F. Tannock
  • Comment |

    During the COVID-19 global pandemic, the cancer community faces many difficult questions. We will first discuss safety considerations for patients with cancer requiring treatment in SARS-CoV-2 endemic areas. We will then discuss a general framework for prioritizing cancer care, emphasizing the precautionary principle in decision making.

    • Timothy P. Hanna
    • , Gerald A. Evans
    •  & Christopher M. Booth
  • Comment |

    The FDA has demonstrated a willingness to expedite access to new cancer medicines by using real-world evidence to support regulatory drug approval. In this article, we explore three recent examples of such approvals and the lessons that can be learned from this collective experience.

    • Michael J. Raphael
    • , Bishal Gyawali
    •  & Christopher M. Booth
  • Comment |

    In 2019, the FDA Oncology Center of Excellence (OCE) approved 11 new drugs and biologic agents, 30 supplemental drug and biologic applications, and four biosimilar applications in oncology. These included two landmark approvals involving collaboration among international regulators as part of OCE Project Orbis, as well as the approval of three novel antibody–drug conjugates.

    • Harpreet Singh
    • , Gideon Blumenthal
    •  & Richard Pazdur
  • Comment |

    As more patients with oncogene-driven non-small-cell lung cancer are treated with targeted therapies, they are joining forces online to form groups that provide support, education and advocacy focused on specific oncogenes. Herein, we discuss how the involvement of these groups in patient-partnered research can benefit both patients and lung cancer research.

    • Merel Hennink
    • , Geert Vandeweyer
    •  & Janet Freeman-Daily
  • Comment |

    Shortages of drugs, including chemotherapeutics, are increasingly common in the USA, and compromise patient care, delay clinical trials and are associated with substantial financial costs. The recent shortage of vincristine, a chemotherapeutic used for most children with cancer and countless adult patients, presents a particularly vexing challenge. Drug shortages can cause patients unnecessary anxiety and challenge clinicians to ration lifesaving medications for which no alternative agent exists. We provide an overview of this problem and discuss potential solutions.

    • Erin R. Fox
    •  & Yoram Unguru
  • Comment |

    New molecular insights occasionally lead to the rapid development of therapeutic agents that improve the outcomes of patients with cancer; however, these breakthroughs can be followed by extensive, empirically driven and often unsuccessful efforts at extending the drug to other indications or combinations. Herein, we describe the clinical development of imatinib, a paradigm of rapid molecularly driven drug development, and advocate for a balanced portrayal of the potential of molecularly targeted therapies for cancer.

    • Benjamin G. Carlisle
    • , Tiger Zheng
    •  & Jonathan Kimmelman
  • Comment |

    Many argue that phase I cancer trials are a therapeutic option for eligible patients. I question this position and offer a more nuanced view that differentiates between types of trials. Patients seeking treatment might legitimately pursue phase I trials, although labelling all phase I trials as therapeutic contradicts the spirit of evidence-based medicine.

    • Jonathan Kimmelman
  • Comment |

    The FDA grants Accelerated Approval when deemed necessary to address an unmet need, with a promise that post-marketing research commitments will be fulfilled and that the approvals will be revisited and eventually changed if clinically meaningful results are reported. Herein, we present a timeline of all Accelerated Approvals granted to immune-checkpoint inhibitors to illustrate three ways in which the FDA has failed to fulfil their part in this social contract.

    • Jennifer Gill
    •  & Vinay Prasad
  • 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
  • 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