Current landscape of immunotherapy in the treatment of solid tumours, with future opportunities and challenges.

Immunotherapy has emerged as a new standard of care, showing survival benefit for solid tumours in multiple disease sites and indications. The survival improvements seen in diseases that were highly resistant to traditional therapies, with a poor prognosis, are unprecedented. Although the benefits observed in clinical trials are undeniable, not all patients derive those benefits, leading to emerging combination strategies and an ongoing quest for biomarker selection. Here, we summarize the current evidence for immunotherapy in the treatment of solid tumours, and we discuss emerging strategies at the forefront of research. We discuss future challenges that will be encountered as experience and knowledge continue to expand in this rapidly emerging field.

Oncology education for Canadian internal medicine residents: the value of participating in a medical oncology elective rotation.

Background: Despite the high incidence and burden of cancer in Canadians, medical oncology (mo) rotations are not mandatory in most Canadian internal medicine (im) residency training programs. Methods: All im residents scheduled for a mo rotation at 4 Canadian teaching cancer centres between 1 January 2013 and 31 December 2015 were invited to complete an online survey before and after their rotation. The survey was designed to evaluate perceptions of oncology, comfort in managing cancer patients, and basic oncology knowledge. Results: The survey was completed by 68 im residents pre-rotation and by 48 (71%) post-rotation. Cancer-related learning was acquired mostly from mo physicians in clinic (35%). Self-directed learning, didactic teaching, and resident or fellow teaching accounted for 31%, 26%, and 10% respectively of learning acquisition. Comfort level in dealing with cancer patients and patients at end of life improved to 4.0/5 from 3.2/5 (p < 0.001) and to 4.0/5 from 3.6/5 (p = 0.003) respectively. Mean knowledge assessment score improved to 83% post-rotation from 76% pre-rotation (p = 0.003), with the greatest increase observed in general knowledge of common malignancies. The 3 topics ranked as most important to learn during a mo rotation were oncologic emergencies, common complications of treatment, and approach to diagnosis of cancer. Conclusions: A rotation in mo improves the perceptions of im residents about oncology and their comfort level in dealing with cancer patients and patients at end of life. Overall cancer knowledge is also improved. Given those benefits, im residency programs should encourage most of their residents to complete a mo rotation.

The evolution of biosimilars in oncology, with a focus on trastuzumab.

Cancer therapy has evolved significantly with increased adoption of biologic agents ("biologics"). That evolution is especially true for her2 (human epidermal growth factor receptor-2)-positive breast cancer with the introduction of trastuzumab, a monoclonal antibody against the her2 receptor, which, in combination with chemotherapy, significantly improves survival in both metastatic and early disease. Although the efficacy of biologics is undeniable, their expense is a significant contributor to the increasing cost of cancer care. Across disease sites and indications, biosimilar agents are rapidly being developed with the goal of offering cost-effective alternatives to biologics. Biosimilars are pharmaceuticals whose molecular shape, efficacy, and safety are similar, but not identical, to those of the original product. Although these agents hold the potential to improve patient access, complexities in their production, evaluation, cost, and clinical application have raised questions among experts. Here, we review the landscape of biosimilar agents in oncology, with a focus on trastuzumab biosimilars. We discuss important considerations that must be made as these agents are introduced into routine cancer care.

Aplastic anemia secondary to nivolumab and ipilimumab in a patient with metastatic melanoma: a case report.

BACKGROUND: Immune checkpoint blockade (ICB) is becoming an increasingly prevalent strategy in the clinical realm of cancer therapeutics. With more patients being administered ICB for a host of tumor types, the scope of adverse events associated with these drugs will likely grow. Here we report a case of aplastic anemia (AA) in a patient with metastatic melanoma secondary to dual ICB therapy. To our knowledge, this is only the second case of AA secondary to dual ICB in the literature, and the first to have a positive patient outcome. CASE PRESENTATION: A 51-year old male with metastatic melanoma was started on dual immune checkpoint blockade, in the form ipilimumab (3 mg/kg) and nivolumab (1 mg/kg). Two weeks following the second cycle, he presented to the emergency department with profound polypipsia, polyuria and fatigue. The patient was diagnosed with diabetic ketoacidosis secondary to immune therapy induced type-1 diabetes and was admitted to the ICU. While in hospital the patient developed a symptomatic anemia and neutropenia. A bone marrow biopsy revealed a markedly hypocellular marrow with trinlineage hypoplasia with no evidence of myelodysplasia, neoplasm or excess blasts. Flow cytometry revealed an inverted CD4+:CD8+ ratio and an absence of hematogones. Taken together the presumed etiology was AA secondary to immunotherapy. The patient was subsequently started in IV methylprednisone 70 mg/day for 8 days, followed by a prednisone taper. This intervention rectified the bicytopenia and to date the patient has shown stable blood counts. CONCLUSION: With the use of ICBs becoming increasingly prevalent in the clinical arena, the number of patients presenting with immune-related adverse events will likely increase. The current case illustrates the need to be vigilant when managing cancer patients receiving ICB. The resolution of this patient's AA with corticosteroids highlights the value of early detection and appropriate treatment of these rare immune-mediated adverse events.

A review of the value of human epidermal growth factor receptor 2 (HER2)-targeted therapies in breast cancer.

The cost of cancer drugs continues to escalate with the rapid development and approval of novel therapies, especially over the course of the last decade. In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, the survival benefits gained by new treatments have been undeniably substantial. It is important to assess the financial value of these therapies for decision making at both the societal and individual level. This information is key for managing resources in resource-limited health care systems, while at the same time supporting patient decision-making and conversations between patient and physicians on cost versus benefit. In this article, we perform a systematic review of cost-effectiveness analyses that have been completed to date on HER2-targeted agents, focussing on those that correlate with standard of care therapy. Our discussion also highlights potential strategies to overcome several limitations associated with measuring value for anticancer drugs.

Posterior reversible encephalopathy syndrome resulting from repeat bortezomib usage.

Bortezomib is a chemotherapeutic agent that acts via proteasome inhibition resulting in cellular apoptosis and inhibition of angiogenesis. Although widely accepted as treatment of multiple myeloma and non-Hodgkin's lymphoma, it has also been shown to be efficacious in a variety of solid tumours such as pancreatic and colonic. Posterior reversible encephalopathy syndrome (PRES) is a neuroradiological syndrome characterised by vasogenic oedema involving the postero-occipital cortical and subcortical white matter resulting in visual disturbances, seizures and altered mental status. Although in most cases PRES is reversible with removal of the provoking condition or drug, if not appropriately recognised and treated it may lead to permanent and life-threatening sequelae such as intracerebral haemorrhage and ischaemic infarction. We report a case of PRES associated with bortezomib therapy and contrast it with four other previously reported cases. Recognition of this potentially severe neurological complication is important with the increasingly widespread use of bortezomib.