News & 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

My husband’s diagnosis with melanoma and our struggle to access effective therapy challenged what I had learnt about medical research. I have since founded a patient network, becoming a vocal advocate for patient-centric drug development. Herein, I discuss some of the lessons I have learnt.

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.

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.

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.

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.

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.

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.

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.

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.

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.