Volume 13 Issue 4, April 2016

The recent FDA approval of MM-398 as a second-line treatment of metastatic pancreatic cancer, based on a 1.9-month overall survival benefit observed in the NAPOLI-1 trial, adds a new therapeutic option for this notoriously difficult-to-treat disease; however, by discouraging clinical trial enrolment, this approval might have negative consequences for the development of novel agents, which remain an essential unmet need.

Accurate and efficient expedited investigational new drug (IND) reporting is a crucial component of clinical research. The FDA, pharmaceutical companies, institutional review boards, and clinical investigators should develop dynamic standardized electronic forms with preferred, predetermined terms to harmonize their practices and to help optimize the quality of clinical research and maximize patient safety.

A meaningful revolution in managing malignant diseases has occurred since the advent of molecular targeted therapies; while some agents have resulted in a clinical benefit, these novel agents are also associated with undesired effects and assessing these risks in the correct context of potential clinical benefit is paramount. The authors overview of the development and toxicity profiles of kinase inhibitors and monoclonal antibodies, with an emphasis on their clinical management, including patient supportive care needs, and the impact of these treatments use on the health-care expenditures at the end of life.

The presence of tumour-infiltrating lymphocytes (TILs) in breast tumours is related to a better prognosis in patients with early stage breast cancer, but the immunobiology of breast cancer remains to be well-characterized. In this Review, the authors discuss how to measure TIL-related parameters in the clinic, as well as their value as a prognostic and predictive biomarker in breast cancer. The rationale for enhancing immunity in breast cancer is also examined.

As the numbers of available anticancer drugs and thus possible drug combinations continues to grow, determining the optimal toxicity–efficacy balance of treatment regimens becomes increasingly complex, and the utility of standard empirical approaches to optimizing drug dosing and scheduling is becoming increasingly limited. Mathematical modelling can substantially advance the development of effective treatment regimens through improved rationalization of therapeutic strategies. In this Review, the authors highlight the achievements that have been made to date in computational modelling of drug regimens, as well as the limitations of this approach. They also discuss the potential future implementation of this strategy to achieve precision medicine in oncology.

Patients with advanced-stage ovarian cancer are widely believed to have a dismal prognosis; however, around 20% of women with this disease survive beyond 12 years after treatment and are effectively cured. In this Perspectives, Steven Narod presents the case that this proportion could be substantially increased through the combination of maximal debulking surgery and intraperitoneal chemotherapy.