News & Views

A minority of patients with gastroesophageal adenocarcinoma derive benefit from immune-checkpoint inhibition (ICI). In a large-cohort phase III study, the nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) arm (which was based on promising preliminary data from CheckMate 032) was closed owing to unacceptably high levels of mortality and morbidity. Our quest for better biomarkers than programmed cell death 1 ligand 1 (PD-L1) and safer dual ICI strategies must continue.

Chemoprevention for patients with Barrett’s oesophagus remains a controversial topic. Results of the first randomized trial of chemoprevention using a proton pump inhibitor with or without aspirin were recently reported. We highlight strengths and weaknesses in the design of the trial and discuss the clinical implications of the findings.

Population-based mammographic screening is widely accepted as an intervention to reduce overall mortality from breast cancer, but at the cost of morbidity due to false positives and substantial overdiagnosis and overtreatment of ultra-low-risk disease, as well as personal and health-economic burdens. Recent data from a modelling study strengthen the rationale for personalized, risk-based screening approaches, now being tested in multiple clinical trials.

The approval of blinatumomab based on achievement of undetectable minimal residual disease (MRD) in patients with B cell acute lymphoblastic leukaemia in complete remission is the first of its kind and raises important considerations. This drug might improve outcomes in this setting, although considerable evidence is needed to validate the performance of MRD as a surrogate end point and confirm the hypothesis.

A recent clinical trial of a virotherapy approach, consisting of an engineered poliovirus, has provided evidence of apparently durable responses in patients with recurrent glioblastoma. The results of this trial and others indicate that virotherapy might be an effective tool in anticancer immunotherapy. Yet, caution must be exercised until appropriately powered randomized clinical trials truly show efficacy.

Comprehensive molecular characterization of infant medulloblastoma has uncovered the high degree of heterogeneity of this disease. Recent results from the SJYC07 study elegantly reveal that risk stratification can be improved if DNA methylation profiling data are incorporated into clinicopathological criteria. Importantly, the delineation of disease subgroups potentially has major clinical implications.

Platinum-based chemotherapy has long been the mainstay first-line therapy for patients with non-small-cell lung cancer without a targetable driver mutation, but has limited effectiveness. Immunotherapy is drastically changing the treatment landscape for this group and improving survival outcomes, with focus turning to frontline immunotherapy combinations.

Accelerated approval enables investigational drugs to reach the US market on the basis of their demonstrated effects in unvalidated surrogate measures, only reasonably likely to predict clinical response. To fulfil the social compromise, regulators should ensure that confirmatory trials testing clinically meaningful end points are already underway at the time of approval.

CARMENA, a trial comparing the efficacy of sunitinib alone to that of nephrectomy followed by sunitinib in patients with primary metastatic renal cell carcinoma who require targeted therapy has demonstrated the non-inferiority of systemic therapy alone. The data provided by this and other studies argue for a lesser role of surgery in the management of these patients.

Developments in the treatment of advanced-stage hepatocellular carcinoma include novel locoregional interventions aiming to induce tumour necrosis and systemic treatments targeting the biological mechanisms of tumour progression, thus aiming to delay progression. These approaches fiercely battle to provide the best survival, but their lack of success to date suggests that they might be better tested as a complementary approach.

PapSEEK, a novel liquid-based cytology test, enabled the highly specific detection of endometrial and ovarian cancer in a retrospective study. Herein, I discuss potential applications of this tool, both for cancer screening of asymptomatic populations and for the early diagnosis of cancer in symptomatic women.

New treatment options for patients with resected stage III melanoma have been established with the publication of the results of four pivotal randomized clinical trials, resulting in three drug approvals, with a forth expected, all within only 4 years. Herein, we put these advances into context.

The prognostic significance of residual disease, measured by flow cytometry or PCR-based assays, has been established in patients with acute myeloid leukaemia (AML). The results of a recent study involving almost 500 patients in morphological remission demonstrate that detection of persistent mutations using next-generation sequencing provides information complementary to that obtained using the established methods and offer insights into AML evolution.

Recent genomic and transcriptomic analyses of diffuse large B cell lymphoma (DLBCL) have provided important new insights into the heterogeneous biology of this disease. The findings provide opportunities to improve treatment strategies, although considerable work is needed to establish and optimize the clinical applicability and utility of molecular classifications of DLBCL.

The affordability of newly approved anticancer agents is a challenge to many national health services and reimbursement systems. Therefore, we have developed an approach based upon the adoption of a novel model of price setting and herein provide examples of how it might be implemented. This model is intended to alter the balance between social and economic entrepreneurship.

Helicobacter pylori eradication therapy is effective in preventing gastric cancer, even in patients with advanced pre-neoplastic lesions (gastric atrophy and/or intestinal metaplasia). We must now focus on how to accomplish the goal of eliminating gastric cancer-related death worldwide; strategies for screening and treatment of gastric neoplasia (primary prevention) and post-treatment surveillance (secondary prevention) are discussed herein.

After almost 20 years of negative trials of novel therapies for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), two androgen receptor antagonists have shown favourable outcomes in phase III trials involving patients with high-risk nmCRPC. Herein, the history of nmCRPC and clinical trials in this disease setting are discussed and a perspective on molecular imaging and clinical management of nmCRPC is offered.

Major advances in our understanding of the molecular pathogenesis of non-small-cell lung cancer (NSCLC) have led to effective targeted therapeutics in several genomically-defined subsets of NSCLC. The recently updated College of American Pathologists, International Association for the Study of Lung cancer, and Association for Molecular Pathology joint guideline, which was endorsed by ASCO, sets new standards for molecular testing in NSCLC.

The biological complexity of triple-negative breast cancers (TNBCs) and the lack of highly recurrent targetable genetic alterations pose major challenges for the implementation of targeted therapies for this disease. A recent multiomic in silico study has identified genetic drivers of five different TNBC molecular subtypes, providing new opportunities for precision medicine approaches.

Patients with solid tumours can have unusual patterns of response to anticancer immunotherapy, necessitating the adaptation of traditional response criteria. A recent retrospective analysis of data from patients with four different types of solid tumours treated with the anti-programmed cell death 1 ligand 1 (PD-L1) antibody atezolizumab confirms the previous experience in patients with melanoma and provides several new insights.