News & Views in 2017

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.

On 30^th 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.

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.

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.

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.

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.

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.

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.

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.

Regorafenib is only the second agent approved by the FDA for the treatment of patients with advanced-stage hepatocellular carcinoma. Herein, we discuss the evidence that led to the approval of this agent. Examination of this process reveals important challenges associated with drug regulation, relating to trial design, treatment toxicity, and real-world clinical benefit.

Response criteria for disease assessment have important therapeutic and prognostic implications in clinical trials and in routine clinical practice. The Lugano classification has been used widely for evaluation of the response of patients with lymphoma to treatment, although the alternative Response Evaluation Criteria In Lymphoma 2017 (RECIL 2017) classification was recently proposed; these criteria are compared herein.

The current standard-of-care therapy for patients with multiple myeloma is autologous stem-cell transplantation; however, whether this approach should be enhanced or displaced by triplet combination therapy is the subject of ongoing debate. We discuss the latest trial that has attempted to address this question and the impact of transplantation and triplet therapy assessment and surrogate end points in future trial design.

Adjuvant ipilimumab is associated with an 11% improvement in 5-year overall survival in patients with high-risk melanoma, but at the cost of considerable toxicity, with half of patients discontinuing treatment owing to adverse events. An analysis of quality-of-life (QoL) outcomes, however, showed little impact of adverse effects of this treatment on QoL, which is puzzling.

Early diagnosis is a key component of melanoma prevention, but diagnostic accuracy varies considerably among clinicians managing patients with potentially suspicious skin lesions. Several tools have been developed to objectively enhance diagnostic assessment and accuracy. Herein, we discuss the potential diagnostic value and limitations of GoogleNet Inception, a new tool for image-based classification of skin lesions.

The Cancer Genome Atlas Research Network recently published the most comprehensive, multi-omic molecular characterization of cervical cancers performed to date. The data reveal novel disease subtypes, and provide new insights into the aetiology and pathogenesis of cervical cancer. Importantly, the information obtained has potentially major clinical implications.

Adoptive cellular therapy (ACT) is now considered a bona fide treatment modality within the evolving field of anticancer immunotherapy. Great advances have enabled the adoptive transfer of tumour-selective lymphocytes for the treatment of a variety of malignancies. Unfortunately, this selectivity has led to the emergence of antigen-loss variants. New strategies need to be employed to minimize the incidence of this phenomenon, enabling the full potential of ACT to be realized.

Fraser and colleagues describe the whole-genome sequencing (WGS) profiles of over 200 localized intermediate-risk prostate cancers. WGS has been widely used in research but not, thus far, in clinical settings. Herein, we consider the possible use of WGS in the field of precision oncology.

The success of cancer therapies is hampered by a paucity of suitable drug targets and the rapid development of therapy resistance. The concept of synthetic lethality provides a potential solution to these constraints via the identification of novel therapeutic vulnerabilities, as exemplified in two recent studies.

Data from the recent Stop 2G-TKI study confirm that around 60% of patients with chronic myeloid leukaemia who discontinue second-generation BCR–ABL1 tyrosine-kinase inhibitor (TKI) therapy after a sustained deep molecular response remain in remission for longer than 1 year. Importantly, the interim findings suggest that prior response to first-line TKI treatment might predict relapse risk after treatment discontinuation.