Reviews & Analysis

Lung-cancer treatment paradigms continue to advance as we exploit our growing understanding of the genetic basis of both tumorigenesis and therapy resistance. Moreover, ongoing developments with targeted therapies are improving patient outcomes, with two new drugs approved in 2015 for non-small-cell lung cancer and many others showing promise.

Advances in key areas of research have enabled improved outcomes for patients diagnosed with ovarian cancer in the past three decades. In 2015, this trend was maintained with important progress in areas such as guideline compliance, design of targeted approaches and molecular profiling.

In 2015, published trials highlighted the remarkable efficacy of docetaxel combined with androgen-deprivation therapy in patients with newly diagnosed metastatic prostate cancer. Also in 2015, a large study revealing potential molecular targets for metastatic castration-resistant prostate cancer therapies was published, along with a study showing activity of PARP inhibition in patients harbouring mutations in genes governing DNA repair.

In a little over the past year, several clinical trials have evaluated new drugs in patients with metastatic colorectal cancer and gastric cancer. Furthermore, genomics studies that attempted to unravel the molecular characteristics of colorectal and gastric cancer were published in 2015. The results of these endeavours will influence clinical practice in 2016 and beyond.

In 2014, no major breakthroughs were made in understanding the biology of breast cancer or its management; few novel practice-changing studies were presented or published. Nevertheless, important negative results from studies that challenge some of the current concepts, particularly in drug development, underline 2014 as a year of 'failed surrogates and precocious expectations'.

Heterogeneity within and across tumours is increasingly recognized as a critical factor that limits therapeutic progress for many cancers. Key studies reported in 2014 describe previously unappreciated patterns of geographical and temporal heterogeneity for glioblastoma (the most-common primary CNS tumour in adults), with important implications for ongoing therapeutic studies evaluating molecular targeted therapies.

The results of several clinical trials in metastatic colorectal cancer presented in 2014 will influence clinical practice. These findings include definitive data from phase III trials comparing bevacizumab and cetuximab-based therapy in the first-line, studies elucidating the value of maintenance therapy after induction treatment, and data on new agents in this disease.

In 2014, developments in our understanding of escape signalling circuits implicated in resistance to targeted agents in patients with lung cancer have led to improvements in tackling such resistance. The potential role for PET in the management of erlotinib therapy, novel combination therapies and pharmacogenomic-driven individualization of platinum-based chemotherapy represent other key advances.

In 2014, strides were made in the care of haematological malignancies. In particular, the heterogeneity of multiple myeloma was unravelled, and new diagnostic criteria and frontline standards of care were proposed; new therapeutic approaches have been validated and approved in chronic lymphocytic leukaemia; and in chronic myeloid leukaemia, complete cytogenetic response was confirmed as the primary therapeutic end point.

In 2013, studies confirmed that HPV infection of target cells predisposes to cervical (pre)cancer. In developed countries, HPV screening revealed superior protection than cytology screening. In India, visual inspection of the cervix after acetic acid application significantly reduced cervical cancer mortality after 12 years. Improved survival for women with advanced disease was observed after adjuvant bevacizumab.

The year 2013 has brought more options for patients with metastatic colorectal cancer (mCRC) with new ways to combine traditional agents, further refinement of predictive molecular for EGFR inhibitors and a new salvage option. Molecular profiling could identify subgroups to further improve treatment selection.

In 2013, the treatment of several NSCLC subtypes was refined. PROFILE-1007 and LUX-Lung 3 confirmed that targeted therapy was superior to chemotherapy, whereas NCIC BR19 and PointBreak failed to show superiority of adjuvant gefitinib and combined maintenance therapy, respectively. These studies reinforced some practices and discouraged others, underscoring the need for new prospective studies.

In 2013, new insights on the molecular features of cutaneous melanoma provided a paradigm shift in our understanding of the biology of this disease. Exploiting immune checkpoint blockade and the use of BRAF-targeted or MAPK-targeted agents contributed to important progress in the treatment and management of cutaneous melanoma.

2013 saw much progress in breast cancer research. Advances in high-throughput technologies continue to refine our knowledge of the molecular biology of breast cancer, and are beginning to give insight into cancer evolution, drug resistance, and how to deploy precision therapeutics.

Next-generation sequencing analysis and characterization of the microenvironment 'field-effect' that promotes hepatocellular carcinoma (HCC) development has revealed critical players and potential targets for chemoprevention. A biomarker-based drug development strategy is needed to improve future HCC clinical trials and therapies.

Gastric cancer is a heterogeneous disease with almost one million new cases occurring annually worldwide. The year 2012 saw important successes and failures in gastric cancer treatment, and also novel insights into the molecular characterization of this disease, which may lead to the development of more-effective targeted therapies.

In 2012, we increased our knowledge of the molecular portrait of breast cancer. The BOLERO-2 and CLEOPATRA trials led to the approval of everolimus and pertuzumab; and the EMILIA trial will likely result in the approval of T-DM1. Some of these findings represent a paradigm shift in the way we think about the biology and management of breast cancer.

In 2012, advances in molecular profiling of primary brain tumours allowed identification of subgroups of glioma and medulloblastoma that were associated with distinct prognoses and predicted treatment response. Adjuvant chemotherapy is now established for 1p/19q co-deleted anaplastic oligodendrogliomas, and may be the preferred treatment in elderly patients with glioblastoma with a methylated MGMT promoter.

In the past year, long-term follow-up of trials have confirmed and disproved paradigms in the treatment of colorectal cancer, and identified a chemoprevention agent. In metastatic disease, chemotherapy in unresected primary tumours was studied, and randomized phase III trials introduced new therapy options. Molecular characterization of colon and rectal tumours offers new drug targets.

Progress was made in major aspects of acute myeloid leukaemia in 2012. Gemtuzumab ozogamicin and decitabine were shown to improve outcomes, relapse after stem-cell transplantation might be prevented by selecting donors according to their KIR genotypes, and next-generation sequencing has provided insights into mutational patterns and disease evolution.