News & Views

  • News & Views |

    The presence and prognostic relevance of the intratumoural microbiota in pancreatic cancer, and the roles of intratumoural bacteria in oncogenesis and therapeutic response are beginning to be elucidated. The feasibility of characterizing intratumoural microbial communities from paraffin-embedded tissues has now been validated, providing greater opportunities for retrospective research. Prospective studies are also needed to test the efficacy of rational approaches combining microbial modulation with chemotherapy and/or immunotherapy.

    • Joshua C. Leinwand
    •  & George Miller
  • News & Views |

    Five randomized trials have been conducted to prove that shorter duration of trastuzumab treatment (9 weeks or 6 months) can replace the standard duration (1 year). The results of PERSEPHONE, the most recent trial, suggest that the efficacy of a 6-month treatment is non-inferior to that of 1 year, although not for all patients. We discuss these results in the context of current treatment standards.

    • Noam Pondé
    •  & Evandro de Azambuja
  • News & Views |

    An urgent clinical need exists to improve the survival of patients with pancreatic cancer through biomarker-driven therapeutic strategies. Such approaches include the targeting of metastatic pancreatic cancer that harbours germline BRCA mutations with poly(ADP-ribose) polymerase inhibitors as maintenance therapy following platinum-based chemotherapy.

    • Shubham Pant
    • , Anirban Maitra
    •  & Timothy A. Yap
  • News & Views |

    In the TITAN and ENZAMET trials, unprecedented overall survival outcomes were observed in patients with metastatic castration-sensitive prostate cancer receiving an agent targeting the androgen receptor in addition to androgen-deprivation therapy early in the course of their disease. Herein, I discuss both trials in the context of other studies in this disease setting.

    • Fred Saad
  • News & Views |

    The addition of the immune-checkpoint inhibitor nivolumab to first-line therapy with doxorubicin, vinblastine and dacarbazine seems feasible, with no signals of severe additional toxicities emerging. The high response rates and acceptable safety profile might make this combination an appealing alternative in the treatment of patients with high-risk disease.

    • Alvaro J. Alencar
    •  & Craig H. Moskowitz
  • News & Views |

    Researchers from Google AI have presented results obtained using a deep learning model for the detection of lung cancer in screening CT images. The authors report a level of performance similar to, or better than, that of radiologists. However, these claims are currently too strong. The model is promising but needs further validation and could only be implemented if screening guidelines were adjusted to accept recommendations from black-box proprietary AI systems.

    • Colin Jacobs
    •  & Bram van Ginneken
  • News & Views |

    The adoptive transfer of T cells expressing a chimeric antigen receptor (CAR) is an effective therapy for patients with relapsed or refractory CD19+ B cell malignancies, but can cause life-threatening toxicities. Herein we discuss a recent study suggesting that alterations to the design of anti-CD19 CARs can reduce cytokine release and the incidence of treatment-related complications.

    • Alexander I. Salter
    •  & Stanley R. Riddell
  • News & Views |

    In a landmark analysis, investigators of the Multicentric Italian Lung Detection (MILD) trial have confirmed 10-year mortality reductions with lung cancer screening using low-dose helical CT (LDCT). These data complement the reduced lung cancer-specific mortality reported in the National Lung Screening Trial and reinforce the rationale for broad implementation of LDCT screening in high-risk populations.

    • Matthew B. Schabath
    •  & Denise R. Aberle
  • News & Views |

    In recent decades, cancer survival has improved dramatically, resulting in a growing population of cancer survivors with chronic health needs and disease risks. While large epidemiological studies are useful in tracking broad trends in health outcomes of cancer survivors, they lack the level of detail needed to inform the delivery of appropriate clinical care and optimal allocation of resources.

    • Eden R. Brauer
    •  & Patricia A. Ganz
  • News & Views |

    Identification of factors predicting recurrence of breast cancer is a long-standing goal, ranging from classical clinicopathological factors through to immunohistochemical assays of receptor levels and, more recently, the expression levels of several genes. A new paper now explores novel expression markers, especially for late recurrence of oestrogen receptor-positive breast cancer.

    • Jack Cuzick
  • News & Views |

    Glioblastoma remains essentially incurable, and new therapeutic approaches are urgently needed. Now, the findings of three serial tissue-based studies suggest that immune-checkpoint inhibition can modify the glioblastoma microenvironment. Following these encouraging observations, the results of two phase III trials of immune-checkpoint inhibition in newly diagnosed glioblastoma, with larger cohorts of patients, are eagerly anticipated.

    • Michael Weller
    •  & Emilie Le Rhun
  • News & Views |

    Using the example of the recently reported phase III MAIA trial, we emphasize herein the requirement to dig deeper into trial designs and end points to determine their appropriateness for the questions at hand and to assess whether a benefit in terms of the primary end point — even if statistically significant and seemingly clinically meaningful — is sufficient to warrant a change in clinical practice.

    • Prashant Kapoor
    •  & S. Vincent Rajkumar
  • News & Views |

    Inhibition of the NKG2A immune checkpoint restores natural killer cell and T cell effector function in preclinical cancer models. In addition, NKG2A blockade in combination with other therapeutic antibodies is showing encouraging responses in a subset of patients with metastatic colorectal or head and neck cancer. However, established biomarkers of response are lacking, and larger trials are needed to enable firm conclusions to be drawn about whether NKG2A inhibition complements existing immunotherapies.

    • Benjamin C. Creelan
    •  & Scott J. Antonia
  • News & Views |

    Recently published data from the ZUMA-1 and JULIET trials suggest that CD19-directed chimeric antigen receptor (CAR) T cell therapy can provide durable remissions, with a low risk of relapse or progression, in 30–40% of patients with relapsed and/or refractory aggressive large B cell lymphoma. Two-year follow-up of the ZUMA-1 clinical trial has not revealed any unexpected toxicities, but further safety monitoring will be needed.

    • David G. Maloney
  • News & Views |

    The first-in-human study of anti-CD47 antibodies blocking CD47–SIRPα interactions in combination with rituximab in patients with non-Hodgkin lymphoma shows encouraging clinical responses accompanied with mild levels of toxicity. Inhibition of the CD47–SIRPα interaction might provide a generic method of promoting the effects of antitumour antibodies in a variety of cancer types. This reveals, for the first time, an innate immune checkpoint as a bona fide target for therapy.

    • Timo K. van den Berg
    •  & Thomas Valerius
  • News & Views |

    The International Society of Paediatric Oncology (SIOP)–Paediatric Oncology in Developing Countries (PODC) Collaborative Wilms Tumour Africa project delivered treatment in eight centres across five countries in sub-Saharan Africa. Setting up a collaboration like this is easier said than done, and herein we share the lessons we learned along the way.

    • Trijn Israels
    •  & Elizabeth M. Molyneux
  • News & Views |

    In a cohort of 100 patients with neuroendocrine cancer, the use of NETest enabled earlier prediction of tumour progression and resulted in a reduction in the frequency of follow-up procedures. These outcomes are exciting and promising, but limited in value by the heterogeneity of the study cohort and by suboptimal assay sensitivity and specificity.

    • Guido Rindi
    •  & Bertram Wiedenmann
  • News & Views |

    The ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) will be useful as a common language to harmonize discussions in precision oncology and could also guide policy and reimbursement decisions, but it is far from perfect. Herein, we highlight how ESCAT can be further improved to increase its utility in clinical and policy decisions.

    • Bishal Gyawali
    •  & Aaron S. Kesselheim
  • 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.

    • Kazuto Harada
    • , Ahmed A. F. Abdelhakeem
    •  & Jaffer A. Ajani
  • News & Views |

    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.

    • Nisreen S. Husain
    •  & Hashem B. El-Serag
  • News & Views |

    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.

    • Laura J. Esserman
    •  & Andrea Z. LaCroix
  • News & Views |

    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.

    • Talal Hilal
    •  & Vinay Prasad
  • News & Views |

    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.

    • Pierpaolo Peruzzi
    •  & E. Antonio Chiocca
  • News & Views |

    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.

    • Marc Remke
    •  & Vijay Ramaswamy
  • News & Views |

    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.

    • Cesare Gridelli
    •  & Francesca Casaluce
  • News & Views |

    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.

    • Bishal Gyawali
    •  & Aaron S. Kesselheim
  • News & Views |

    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.

    • Axel Bex
    •  & John Haanen
  • News & Views |

    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.

    • Marco Sanduzzi-Zamparelli
    •  & Jordi Bruix
  • News & Views |

    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.

    • Usha Menon
  • News & Views |

    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.

    • Alexander M. M. Eggermont
    • , Caroline Robert
    •  & Antoni Ribas
  • News & Views |

    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.

    • Roland B. Walter
    •  & Frederick R. Appelbaum
  • News & Views |

    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.

    • Sydney Dubois
    •  & Fabrice Jardin
  • News & Views |

    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.

    • Carin A. Uyl-de Groot
    •  & Bob Löwenberg
  • News & Views |

    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.

    • Yoshio Yamaoka
  • News & Views |

    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.

    • Celestia S. Higano
  • News & Views |

    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.

    • Chul Kim
    •  & Giuseppe Giaccone
  • News & Views |

    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.

    • Fresia Pareja
    •  & Jorge S. Reis-Filho
  • News & Views |

    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.

    • Patrick A. Ott
  • News & Views |

    Despite the rising incidence of cancer in low-income and lower-middle-income countries, very few oncologists are present in these regions — or, in some areas, even none. However, limited evidence of the global oncology workload inequity is available in the literature. Herein, we summarize recent findings that shed some light on this problem and discuss potential oncology workforce solutions.

    • Temidayo Fadelu
    •  & Lawrence N. Shulman
  • News & Views |

    Patients value anticancer therapies that provide durable clinical responses; immune-checkpoint inhibitors can provide such benefit for patients with some advanced-stage malignancies, albeit only for a minority of those treated. Modern oncology value frameworks have set efficacy thresholds in an attempt to assess the clinical benefit of anticancer therapeutics. But, is the benefit of durable cancer control reflected in these thresholds?

    • Joseph C. Del Paggio
  • News & Views |

    Recently published data from a large-cohort study confirm the substantial burden of chronic health conditions among childhood cancer survivors, and describe the multiple chronic conditions faced by these individuals. The findings emphasize the need for specialized care in this unique patient population that, as discussed herein, often goes unmet. More must be done to ease the burden on cancer survivors; new models of care are required to improve their long-term health.

    • Tara O. Henderson
    •  & Kevin C. Oeffinger
  • News & Views |

    Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease for which treatment has, historically, lagged behind that of other solid tumour types. A more detailed understanding of the biology of individual tumours, and the identification of molecular features providing prognostic and predictive information is key to the application of personalized care for patients with MIBC. The publication of a study of 412 samples now provides such data.

    • Carolyn D. Hurst
    •  & Margaret A. Knowles
  • News & Views |

    On 30th August 2017, tisagenlecleucel became the first chimeric antigen receptor (CAR)-T-cell therapy to be approved by the FDA. This approval has important implications for health-care systems because the use of this promising treatment presents considerable logistical, toxicological, and financial challenges. Moreover, the high price tag of US$475,000 is questionable, considering the major role of US taxpayers in covering the development, delivery, and supportive-care costs of this treatment.

    • Vinay Prasad
  • News & Views |

    The development of therapeutic cancer vaccines has been pursued for many decades. Many vaccines can elicit immunity to tumour antigens, although their clinical efficacy remains modest. Recent results from two clinical trials highlight the potential of personalized vaccination strategies, made possible by high-throughput approaches to the identification of immunogenic tumour neoantigens. Thus, therapeutic cancer vaccines might soon move into the mainstream.

    • Jacques Banchereau
    •  & Karolina Palucka
  • News & Views |

    Updated results from the EMILIA and TH3RESA trials in patients with advanced-stage HER2-positive breast cancer confirm the overall survival benefit and favourable safety profile of T-DM1 after prolonged follow-up durations. The efficacy of T-DM1 as a second or later line of treatment indicates that HER2 is a relevant therapeutic target throughout the course of the disease.

    • Otto Metzger-Filho
    •  & Eric P. Winer
  • News & Views |

    Potential strategies for improving the outcomes of patients with early stage HER2-positive (HER2+) breast cancer have included dual anti-HER2 therapy. Recent results from the APHINITY trial show a statistically significant, but clinically modest, benefit from the addition of pertuzumab to trastuzumab and chemotherapy. Subsequent trials should focus on biomarkers to identify patients with HER2+ breast cancer who require more-intensive or less-intensive therapy.

    • Sasha E. Stanton
    •  & Nancy E. Davidson
  • News & Views |

    First-line, potent androgen blockade for patients with newly diagnosed, advanced-stage, castration-sensitive prostate cancer is confirmed as an effective strategy by data from the STAMPEDE and LATITUDE trials. Herein, we highlight the benefits, discuss caveats and consider the clinical care implications of these findings.

    • Anis A. Hamid
    •  & Christopher J. Sweeney
  • News & Views |

    Patients with metastatic soft-tissue sarcoma can benefit from systemic therapy, but the best drug combinations for the different disease subtypes remain to be established. Recently, great emphasis has been placed on histology-based chemotherapy regimens. Herein, we discuss the results of a recently published study demonstrating that some of these regimens are not superior to standard-of-care chemotherapy in the neoadjuvant setting.

    • Robin L. Jones
    •  & Khin Thway
  • News & Views |

    Important biological questions can be addressed by interrogating the transcriptomes of cancer cells. In a recently published landmark study, Giustacchini and collaborators used a single-cell approach to analyse mRNA of cancer cells derived from patients with chronic myeloid leukaemia. Herein, we discuss how this approach could be used to address relevant clinical questions.

    • Sam Behjati
    •  & Muzlifah Haniffa
  • News & Views |

    In 2016, results of an important randomized trial demonstrated that patients undergoing chemotherapy who reported symptoms electronically have a better quality of life than those receiving usual care. Now, a significant survival improvement for patients in the experimental arm of this study has been reported. The emphasis of this survival benefit is 'culturally' positive, promoting the adoption of patient-reported outcomes in clinical practice.

    • Elisa Sperti
    •  & Massimo Di Maio