Comment

Some of the most consequential conflicts in oncology and medicine overall are not financial; these remain poorly defined and weakly regulated. Here we offer a policy-relevant definition and examine how reputation, ambition, ideology and institutional loyalty can shape research, guidelines, policy and hiring decisions. We argue for structural safeguards to preserve trust in medicine.

Drug-induced interstitial lung disease (DIILD) is emerging as a hidden toll of modern oncology. Diagnosis of DIILD is confounded by non-specific symptoms and the absence of validated biomarkers, leaving clinicians to navigate heterogeneous, drug-specific guidelines. Herein, we discuss this predicament and advocate a shift from reactive management towards proactive survivorship.

Many women ≥75 years of age continue to undergo screening for breast cancer despite a lack of evidence supporting this practice. Evidence from the past 5 years suggests rising rates of breast cancer diagnosis in this age group without a corresponding increase in survival — either because the tumour itself is biologically indolent or because life-limiting comorbidities render a biologically aggressive tumour unlikely to further reduce life expectancy. Here, we review what we know, and what we do not know, about screening and overdiagnosis of breast cancer in women ≥75 years of age and build a case for active monitoring for selected screen-detected breast cancers in this population.

Oncologists have crucial yet under-studied and often under-supported roles in promoting clinical trial referral and enrolment. Herein, we advocate for a systemic shift that acknowledges the operational barriers oncologists face and enhances structural support through streamlined workflows and behavioural science-informed strategies to facilitate their participation in clinical trial enrolment.

In pivotal trials testing daratumumab in patients with transplant-ineligible newly diagnosed multiple myeloma, inadequate crossover provisions have not only compromised the interpretation of survival data but also left fundamental questions about optimal treatment sequencing unanswered. Herein, we address the ethical implications of trial designs that fail to guarantee access to effective post-progression therapy for patients in the control arm, particularly in studies across regions in which standard-of-care treatment varies dramatically.

In 2024, the US FDA approved several new agents for the treatment of patients with cancer, including small-molecule inhibitors, immune-checkpoint inhibitors, bispecific antibodies, antibody–drug conjugates and cell and gene therapy products. Areas of regulatory focus included the accelerated approval programme and diligent completion of post-marketing trials, convening of Oncologic Drugs Advisory Committee meetings to ensure transparent discussions of complex regulatory issues, and continuation of robust, meaningful engagement with the oncology community to foster efficient drug development.

First-line treatment of advanced-stage classic Hodgkin lymphoma (HL) has successfully entered the era of targeted agents based on results from the phase III German Hodgkin Study Group HD21 and US intergroup S1826 trials. Although these trials bring about important advances, many uncertainties remain and the outcomes of all patients with HL can be further improved.

Patients with advanced-stage cancer seek treatments that prolong survival and improve quality of life. We analysed new anticancer drug indications approved by the FDA and EMA between 2020 and 2023 using the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale quality-of-life checklist. Our findings highlight critical gaps in the availability and reliability of quality-of-life outcomes from the pivotal trials that support these approvals.

The BCMA-targeted chimeric antigen receptor (CAR) T cell therapy ciltacabtagene autoleucel (cilta-cel) has demonstrated exceptional efficacy in studies conducted worldwide, which has resulted in regulatory approvals in >40 countries. Herein, we examine the regulatory pathways that led to its approval in different regions, focus on challenges in clinical development and regulatory submission, and provide insight into strategies for advancing innovative cell therapies.

Paediatric acute myeloid leukaemia (AML) highlights the challenges of drug development for rare diseases, in which limited patient numbers and substantial heterogeneity hinder progress. Traditional one-size-fits-all randomized trials are ineffective. Nonetheless, tailored therapies and biomarker-driven studies can improve outcomes and transform the treatment of paediatric patients with AML and potentially other rare cancers.

Despite recent FDA approval, the clinical utility of vorasidenib in the treatment of IDH-mutant low-grade gliomas remains unclear. Herein, we critique the pivotal trial of vorasidenib, and highlight the questionable choice of control intervention and end points, ethical concerns, as well as the uncertain efficacy observed, and argue that the approval might be premature given the high cost of this drug and lack of clear benefit over standard treatments.

Precision oncology has reached a milestone as data from two trials in which molecular profiling guided both site-specific and tumour-agnostic therapies indicate improved survival outcomes in patients with cancer of unknown primary. These findings can also be extrapolated and support the use of tissue-agnostic approaches in general, and also suggest that the tissue of origin might have a role in the agnostic classification of cancers and their response to treatment.

My close experience with cancer and interactions with other patients, caregivers and health-care providers have shaped my belief that patients must be at the centre of research and care. In this Comment, I advocate for a redirection of research efforts in order to measure patient-centred outcomes and address health disparities.

The question of whether chimeric antigen receptor (CAR) T cell therapies should be used in earlier lines (after 1–2 prior lines of therapy) in patients with relapsed and/or refractory multiple myeloma remains unanswered. Herein, I argue that the use of surrogate end points that lack a robust correlation with overall survival, as well as suboptimal control arms and use of post-progression therapies, limit the ability to make definitive conclusions on the basis of the available data.

Certain subsets of patients with multiple myeloma or its precursor conditions are overtreated with current approaches to therapy. Herein, we highlight several key areas where we believe de-escalation of treatment is needed. Dedicated trials to assess these de-escalation approaches and urgent changes to current clinical practices are needed.

In 2023, the US FDA approved several new cancer drugs and biologic agents, including seven small-molecule inhibitors, four bispecific T cell engagers, two anti-PD-1 antibodies and one cell therapy product. Regulatory focus areas included analyses of biomarker-positive subgroups that drive efficacy, equipoise in randomized controlled trials and a new authority to require confirmatory trials be underway before accelerated approval.

The US FDA Accelerated Approval of sotorasib required the sponsor to conduct a randomized trial that compared the safety and efficacy of the approved dose with a lower dose. These results, recently disclosed, have important implications for patients, payers, oncologists and the pharmaceutical industry.

The FDA approval of perioperative pembrolizumab, an approach that combines neoadjuvant and adjuvant therapy with this agent, for patients with early stage non-small-cell lung cancer (NSCLC) contradicts its own stated standard for combination therapies. Given the large population of patients with early stage NSCLC and the high costs of pembrolizumab, whether the adjuvant component provides incremental benefit is an important question.

Through Project Optimus, the FDA calls for radical changes in the design of early phase trials to identify the optimal doses of oncology drugs to achieve maximal efficacy with better tolerability and patient acceptability. Herein, we discuss approaches that will enable the implementation of this initiative as well as some concerns that the draft guidance has raised in the oncology community.

Projected increases of cancer-attributable health-care costs, accompanied by staff shortages, will impose future economic and operational challenges on national health-care systems. Herein, we highlight a series of clinical and health economic rationales in support of publicly funded clinical trial teams that conduct real-world dose-reduction trials aiming for adjustment of cancer drug label doses to reduce not only the financial burden on payers, but also the toxicity burden on patients.