Browse Articles

Recent results from the FLAURA2 and MARIPOSA-2 trials underline the continued role of chemotherapy in the treatment of patients with EGFR-mutated non-small-cell lung cancer in the era of targeted therapies. Herein, we argue that the most appropriate and rational sequence and/or combination of therapies remains a matter of discussion.

The current standard-of-care adjuvant treatment for patients with colorectal cancer is chemotherapy selected on the basis of conventional histopathological staging criteria; however, the clinical benefit from these regimens is limited. The authors of this Perspective discuss strategies to minimize toxicity and monitor efficacy of these regimens, and propose new tools for disease staging that could enable more personalized treatment decisions.

Neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy with pelvic lymphadenectomy is the current standard therapy for cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC). A phase II trial testing treatment intensification by adding the immune-checkpoint inhibitor nivolumab to chemotherapy has yielded promising complete response rates, which suggests that bladder-preserving treatment could become attainable in selected patients. This trial heralds a new era in demonstrating the feasibility of bladder preservation for selected patients with MIBC.

Patients with advanced-stage urothelial cancer (aUC) continue to have poor long-term survival outcomes. However, developments in the past 5 years, most notably the availability of maintenance therapy with the anti-PD-1 antibody avelumab, are beginning to change this issue. In this Review, the authors provide an overview of the treatment of patients with aUC, including considerations of the various promising new therapeutic modalities and how they might improve clinical outcomes.

Identifying patients who are likely to benefit from immune-checkpoint inhibitors remains one of the major challenges in immunotherapy. Cancer immunogenomics is an emerging field that bridges genomics and immunology. The authors of this Review provide an overview of the computational approaches currently available to analyse bulk tissue and single-cell sequencing data from cancer, stromal and immune cells.

Despite some success in patients with certain B cell malignancies and relapsed and/or refractory multiple myeloma, studies testing chimeric antigen receptor (CAR) T cells in patients with advanced-stage solid tumours have been largely unsuccessful, with a few notable exceptions. In this Perspective, the author provides some possible reasons for the failures of most CAR T cell-based approaches and suggests strategies that might address some of these challenges.

Hepatocellular carcinoma (HCC) is among the most common causes of cancer-related death globally, and despite improvements in prevention and treatment strategies, continued increases in HCC incidence and mortality are predicted. Cirrhosis remains the major risk factor for HCC, although the underlying aetiology is shifting from virus-related to non-viral liver diseases. In this Review, the authors discuss the changing trends in HCC epidemiology and their implications for screening, prevention and therapy, including opportunities to further improve the management of patients with, or at high risk of, HCC.

PRO-TECT is a randomized trial that innovatively integrated financial toxicity screening into a pre-existing digital symptom-monitoring programme, enabling longitudinal detection of financial toxicity. Such a strategy provides an unobtrusive and cost-effective method for early detection and mitigation of financial toxicity by aligning the needs of patients and carers with the resources available in community clinical practices.

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.

According to the precision oncology paradigm, cancer therapies are increasingly being matched to specific sensitizing alterations using a biomarker-directed approach. However, the criteria for determining the actionability of molecular alterations and selecting matched treatments evolve over time. Molecular tumour boards (MTBs) have emerged as means to capitalize on the collective knowledge of various experts to interpret molecular-profiling data and to eliminate subjectivity in treatment selection. This Review describes the components, processes and increasingly important role of MTBs in optimizing the implementation of precision oncology in both clinical trials and clinical practice, as well as current and future considerations for ensuring the sustainability of MTBs and expanding their outreach to underserved populations.

The use of composite end points in clinical trials can expedite drug development and approval, and thus improve patient access to novel treatments, but are often vaguely and heterogeneously defined, with considerable inter-study variation in the component events that are included. The different component events can vary in clinical significance and be differentially affected by treatment but, nevertheless, are rarely reported separately. In this Perspective, Walia et al. define composite outcomes that are commonly used in oncology, discuss the advantages and challenges of using composite end points, and advocate for transparent reporting including a full breakdown of the component events to facilitate accurate interpretation of trial results and the true benefit of an intervention.

Epstein–Barr virus (EBV)-based biomarkers are used for nasopharyngeal carcinoma (NPC) screening in endemic regions. A recent prospective study describes the use of a new serological biomarker, antibodies targeting the EBV protein BNLF2b, for NPC screening in >20,000 participants. This biomarker yielded both higher sensitivity and specificity for NPC detection in the screening cohort compared with the conventionally used antibodies. Herein, we highlight the key findings of this study and discuss the implications of these results.