News & Views in 2014

With no large randomized phase III trials to provide definitive answers, the ideal number of platinum-based chemotherapy cycles in patients with advanced non-small-cell lung cancer has long been unclear. Most guidelines recommend a maximum of 4–6 cycles. Rossi and colleagues now suggest that four chemotherapy cycles is the optimal regimen.

Although radiotherapy is a key component of cancer treatment, provision of this modality is not immune to limits placed on health-care expenditure. Recent studies suggest European radiation oncology resources will generally be insufficient to meet future, and in some cases current, needs. This challenge and how it might be addressed is discussed herein.

The RAINBOW study has demonstrated that ramucirumab plus paclitaxel as second-line treatment for advanced-stage gastric cancer prolongs survival compared with paclitaxel alone. These data confirm that ramucirumab represents a new effective treatment option for gastric cancer. Nevertheless, new treatment options remain eagerly awaited in this disease with dismal outcomes.

Adoptive immunotherapy using T cells genetically engineered to express a chimeric antigen receptor that targets CD19, a B-cell differentiation antigen, has demonstrated impressive efficacy in a range of B-lymphoid malignancies. The latest results demonstrate the potential of this approach in patients with chemotherapy-refractory diffuse large B-cell lymphoma.

Two large randomized trials have advanced our knowledge of myeloma care. The first study reported that autologous stem-cell transplantation remains the frontline therapy for transplant-eligible patients with multiple myeloma in the current era of novel agents. Together, this study and the second large trial in transplant-ineligible patients demonstrate the value of maintenance treatment with continuous lenalidomide.

The Collaborative Wilms Tumour Africa Project comprises eight centres in sub-Saharan Africa, which are implementing a treatment guideline that has been developed for local conditions. Uniform outcome evaluation, communication and training are all part of the project remit and will ultimately serve to improve cancer care for children in Africa.

Over the past decade, funding for cancer research by the US government—and others—has stagnated, while the demand for investment has grown because of the increasing cancer incidence worldwide. We discuss how National Cancer Institute funding efforts have developed during this period, and the contemporary and future impact of these measures on cancer research in the USA.

It has been a decade of remarkable progress in the field of haematological malignancies with the rapid translation of basic science discoveries into effective targeted therapies. We discuss the most exciting advances in this field, many of which have already produced meaningful improvements in survival and quality of life of patients.

By November 2004, when the first issue of Nature Reviews Clinical Oncology was published, cancer immunotherapy had been successfully applied to the treatment of selected human cancers; however, dramatic progress in the following decade has moved immunotherapy from the sidelines of cancer treatment into the mainstream of modern oncology.

Over the past decade, there have been profound shifts in clinical trial design. Phase II randomized studies, phase II/III and other adaptive designs, early surrogate end points, and prospective biomarker-based patient selection have all increased in popularity. We discuss these shifts in clinical trial designs that have increased efficiency in identifying which patients will benefit from specific treatments.

The rise of targeted therapy for solid tumours over the past decade has yielded a cornucopia of novel agents across an array of cancers. Amidst multiple acclaimed successes, targeted therapies are associated with considerable toxicity, and durable responses are often thwarted by genomic chaos driving the evolution of resistant clones; key examples of successes in solid tumours are highlighted herein.

Over the past decade, genetic testing for rare inherited mutations, such as BRCA1 and BRCA2 mutations, has been successfully incorporated into clinical practice. Next-generation sequencing of cancer-susceptibility genes and entire tumour genomes has transformed cancer care and prevention. The discoveries of new cancer syndromes have raised exciting opportunities and potential liabilities for cancer-care providers seeking to incorporate genomic approaches into preventive oncology practice.

Several clinical trials have investigated the antitumour effect of bisphosphonates when used as adjuvant treatment for early stage breast cancer. Among these, the results of the AZURE trial, although negative, highlight the potential benefit of treatment with zoledronic acid in postmenopausal women with high-risk early stage breast cancer.

The cancer community is deeply concerned about the unintended consequences of the current wording of the European Union (EU) draft Regulation on Data Protection, which may challenge the survival of retrospective clinical research, biobanking, and population-based cancer registries in the EU. This directive could negatively affect Europe's competitiveness in cancer research.

Hepatocellular carcinoma is a difficult-to-treat cancer and, after numerous phase III trials assessing kinase inhibitors have failed to meet their end points, sorafenib is the only accepted treatment for advanced stages of the disease. Now, the trial EVOLVE-1 has shown a lack of benefit for everolimus in the second-line treatment setting.

Cytotoxic agents are conventionally dosed on the basis of the maximum tolerated dose defined in phase I trials. A study assessing adverse events in over 2,000 patients treated with molecularly targeted agents suggests a need to redefine criteria for dosing of molecularly targeted agents, which should be based on randomized, dose-ranging phase II trials.

The PREVAIL trial compared enzalutamide and placebo in patients with metastatic castration-resistant prostate cancer who had not received prior chemotherapy, demonstrating an improvement in overall survival and other clinical, radiographic, and biochemical outcomes. Herein, the implications of these data in the rapidly changing landscape of metastatic prostate cancer therapy are discussed.

The decision of patients with breast cancer to have contralateral mastectomies is often related to their genetic risk. However, the increasing frequency of this surgical approach is also associated with social and psychological issues such as celebrity experiences and fear of contralateral breast cancer. Appropriate counselling may better inform patients' surgical choices.

Healthy individuals carrying the t(14;18) translocation might never develop follicular lymphoma (FL). However, individuals with more than 1 in 10,000 cells carrying this translocation are at high-risk of developing FL. The identification of this high-risk population will help define the pathways driving FL and designing targeted therapies to use before its development.

The recent results of the Early Breast Cancer Trialists' Cooperative Group meta-analysis have demonstrated that post-mastectomy radiotherapy reduces breast cancer recurrence and mortality in women with positive axillary lymph nodes—independently from the number of the lymph nodes involved—with no significant effect in patients with node-negative axillary status.