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Key Points Development of vaccines for the treatment of cancer has posed many challenges, but results from some recent studies have confirmed the potential for clinical benefit Progress has been driven by advances in our understanding of cancer immunology and, in particular, the nature and dynamics of the tumour microenvironment Many clinical trials may have failed to adequately account for how vaccines differ from other cancer therapies, and for immunosuppressive mechanisms that operate in the tumour microenvironment Predictive biomarkers that can identify subpopulations of patients most likely to benefit from active immunotherapy are needed Evidence from clinical trials suggest that clinical benefit might be greatest in patients with less advanced-stage malignancies Future strategies should include steps to modify the tumour microenvironment to optimize tumour-specific immune responses Active immunotherapy is emerging as an important addition to conventional cancer treatments, but many important questions remain. Optimal combinations of antigens, adjuvants and delivery vehicles need to be determined and effective strategies for overcoming tumour-associated immunosuppression ought to be developed. This Review provides an overview of new results from clinical studies of therapeutic cancer vaccines directed against tumour-associated antigens and discusses their implications for the use of active immunotherapy. The therapeutic potential of host-specific and tumour-specific immune responses is well recognized and, after many years, active immunotherapies directed at inducing or augmenting these responses are entering clinical practice. Antitumour immunization is a complex, multi-component task, and the optimal combinations of antigens, adjuvants, delivery vehicles and routes of administration are not yet identified. Active immunotherapy must also address the immunosuppressive and tolerogenic mechanisms deployed by tumours. This Review provides an overview of new results from clinical studies of therapeutic cancer vaccines directed against tumour-associated antigens and discusses their implications for the use of active immunotherapy.

As originator biologic medicines lose patent protection, some biopharmaceutical companies are focusing on developing similar versions of these costly and complex therapies with a goal of providing more affordable treatment options. Many of these molecules, known as biosimilars, are now approved worldwide and several more are expected to be introduced in the near future. As more biosimilars become available, it is important for clinicians to become familiar with this new category of products and understand how biosimilars are developed, how their development differs from that of originator biologics and how they differ from generics. This review aims to provide the practicing clinician with the knowledge needed to understand biosimilars, along with some guidance on their use in treating oncologic diseases.

INTEREST has established that the survival of previously treated patients with non-small-cell lung cancer who received the epidermal-growth-factor receptor (EGFR) tyrosine kinase inhibitor gefitinib was non-inferior to those treated with docetaxel, with reduced toxicity and improved quality of life. Recently, detection of mutations in circulating cells from patients with non-small-cell lung cancer has supported the view that such differences occur.6 However, the non-randomised and placebo-controlled studies that generated the hypotheses on biomarkers and EGFR tyrosine kinase inhibitors were also done on similarly archived tissue samples.

Small cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis. It can be very sensitive to radiation and cytotoxic chemotherapy and is potentially curable if all sites of disease can be encompassed in a radiation field. For the vast majority of patients relapse is the norm, with only limited gains from further lines of chemotherapy. In spite of the recognition of a number of molecular targets based on preclinical studies, targeted therapy for small cell lung cancer has yet to demonstrate any significant clinical benefit. This review summarizes the various targeted pharmacological approaches employed with a view to extending survival in extensive stage SCLC or improving on remission induction in limited stage disease. Pharmacological agents have targeted aberrant signal transduction pathways, proteins involved in cell cycle progression, apoptosis and angiogenesis. Additionally, immunomodulatory approaches have been used to stimulate an immune response against tumor associated antigens. Though the clinical data thus far is discouraging, drugs are still undergoing evaluation and more targets continue to be identified. There is considerable scope for further research and in particular combining newer therapies with existing treatment modalities to improve outcomes.

The introduction of recombinant human erythropoietin (rHuEPO) has proven to be a major advance in the therapeutic options available for managing anemia in cancer patients. The results of placebo-controlled clinical trials and large, community-based, open-label studies have confirmed that epoetin alfa, a recombinant human erythropoietin, significantly reduces transfusion requirements, and reliably increases hemoglobin (Hb) levels in anemic (Hb level <12 g/dl) cancer patients undergoing chemotherapy. Increased Hb improves patients’ energy level and their ability to perform the activities of daily living, as well as their overall quality of life (QOL). These findings are independent of tumor type and disease status and are comparable in patients receiving nonplatinum- and platinum-based chemotherapeutic regimens. Furthermore, more than a decade of use in clinical trials and by physicians in routine clinical practice has demonstrated that epoetin alfa is safe and well tolerated when used to treat cancer patients with anemia. The availability of epoetin alfa as an alternative to transfusion has changed practices in anemia management; physicians can now treat anemia with the goal of achieving adequate Hb levels to relieve anemia-related fatigue, a major symptom contributing to decreased QOL in cancer patients. Incremental benefit analysis has shown that increasing Hb level from 11 g/dl to 12 g/dl yields the greatest improvement in QOL per 1 g/dl increase in Hb. The demonstrated efficacy of epoetin alfa for increasing Hb levels and improving patient QOL have made this agent a rationale choice for management of cancer-related anemia. Ongoing research will continue to provide new insights into best management of anemia with epoetin alfa in cancer patients.

The clinical development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for treatment of non-small cell lung cancer (NSCLC) is a major breakthrough in the field. Erlotinib is the first of this class of drug demonstrated in a placebo-controlled trial to prolong survival of patients with previously treated NSCLC. The challenge now is how best to select patients for this treatment. Clinical factors including female gender, East Asian ethnic origin, adenocarcinoma histology, and a history of never-smoking are associated with better response rates, but response to erlotinib is not exclusive to these populations or essential for a survival benefit. Molecular factors such as EGFR mutation and increased EGFR gene copy number provide objective tests that may be superior to clinical factors for patient selection, but assay for these factors is crucially dependent on available tumor tissue and to date, there are no published data from randomized trials where tumor tissue is available from all patients. Here we review the clinical and biological factors that may be applied to select patients for treatment with EGFR-TKIs and conclude that the available data are premature for definitive guidelines to select against an EGFR-TKI.

To establish whether temozolomide is more effective against A375M human melanoma xenografts if given every 4 h rather than every 24 h, in order to exploit depletion of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (ATase) by prior doses of the drug. ATase depletion in A375M human melanoma xenografts was determined over 24 h after a single dose of temozolomide. The effect of different drug schedules (all of total dose 500 mg/kg) in delaying the growth of the xenografts was tested, and ATase depletion and DNA methylation damage assessed in tumour and normal tissue. Maximal depletion of ATase in tumour, to 2.52 +/- 0.23% of pretreatment levels, occurred 4-8 h after a single 100 mg/kg i.p. dose of temozolomide, with 23.0% recovery of protein levels at 24 h. Scheduling of temozolomide every 4 h increased tumour growth delay (33.6 +/- 1.39 days with temozolomide 100 mg/kg 4-hourly x versus 23.2 +/- 1.43 days with temozolomide 100 mg/kg once daily x 5; P < 0.0001) at the expense of increased toxicity (17.4 +/- 1.55% animal weight loss versus 10.6 +/- 1.27%. respectively). Temozolomide every 4 h did not increase ATase depletion compared with the 5-day schedule, but resulted in greater DNA 06-guanine methylation (29.0% more in tumour, 20.8% in liver and 56.0% in brain, comparing areas under the methylation-time curve). The 4-hourly schedule of temozolomide delayed tumour growth significantly more than the once-daily and 12-hourly schedules, probably as a result of greater DNA damage inflicted, but also increased toxicity. It remains to be seen if this regimen confers a net benefit over the standard schedule.