Antibody–drug conjugates (ADCs) have provided new therapeutic options and significant promise for patients with cancer, particularly where existing treatments are limited. Substantial effort in ADC development is underway globally, with 13 ADCs currently approved and many more in development. The therapeutic benefits of ADCs leverage the ability to selectively target cancer cells through antibody binding, resultant relative sparing of non-malignant tissues, and the targeted delivery of a cytotoxic payload. Consequently, this drug class has demonstrated activity in multiple malignancies refractory to standard therapeutic options. Despite this, limitations exist, including narrow therapeutic windows, unique toxicity profiles, development of therapeutic resistance, and appropriate biomarker selection. This review will describe the development of ADCs, their mechanisms of action, pivotal trials, and approved indications and identify common themes. Current challenges and opportunities will be discussed for this drug class in cancer therapeutics at a time when significant developments in antibody therapies, immunotherapy, and targeted agents are occurring.

Exceptional response to olaparib in a case with Fanconi anemia and metastatic esophageal carcinoma

Endocrine therapy forms the backbone of systemic therapy for the majority of persons with early and late-stage breast cancer. However, the side effects can negatively affect quality of life, and impact treatment adherence and overall oncological outcomes. Adverse effects on cognition are common, underreported and challenging to manage. We aim to describe the nature, incidence, risk factors and underlying mechanisms of endocrine therapy-induced cognitive dysfunction. We conducted a comprehensive literature review of the studies reporting on cognitive dysfunction associated with endocrine therapies for breast cancer. We also summarise prevention and treatment strategies, and ongoing research. Given that patients are taking endocrine therapies for longer durations than ever before, it is essential that these side effects are managed pro-actively within a multi-disciplinary team in order to promote adherence to endocrine therapy and improve patients’ quality of life.

BACKGROUND:As treatments for rectal cancer improve with developments in surgical techniques, radiotherapy and chemotherapy, the nature of recurrences are evolving. We used a comprehensive database of a large Australian population with stage I-III rectal adenocarcinoma to identify timing and prognostic significance of recurrences, and factors associated with risk of developing recurrent disease.METHODS:All patients with locoregional rectal cancer treated with curative intent in our health district from 2006 to 2017 were included. Multivariate analysis using Cox regression models were used to identify factors associated with recurrence.RESULTS:A total of 483 patients were included. Recurrence occurred in 117 (24.2%) of 483 patients, being locoregional in 15 (3.1%) patients, distant in 85 patients (17.6%) and both locoregional and distant in 17 (3.5%) patients. Compared to those with locoregional recurrence, those with both locoregional and distant recurrence had worse cancer-specific survival. On univariate analysis, factors associated with recurrence included stage, grade, radiotherapy, chemotherapy, surgery type and distal tumour location. Factors which remained significant on multivariate analysis included higher grade and stage.CONCLUSION:In the era of multimodality therapy for rectal cancer, recurrences are predominantly distant. Traditional predictors including higher stage, grade and distal tumour location remain independently associated with recurrence, despite current treatment paradigms.

OBJECTIVES:Central venous access is needed to facilitate chemotherapy for many cancer patients. Central venous catheter-related thrombosis (CVCT) is a major complication that can cause significant morbidity and mortality. We sought to explore the rate of CVCT in a general cancer population in Australia and to identify factors associated with increased risk of thrombosis. DESIGN:This is a multi-centre retrospective cohort study. SETTING AND PARTICIPANTS:We analysed key patient, treatment, and cancer-related factors for 317 patients with cancer and central venous catheters inserted for systemic therapy. MAIN OUTCOME MEASURES:Symptomatic CVCT confirmed with imaging and management of patients with CVCT. RESULTS:A total of 402 cases of central line insertion were analysed. Central venous catheter-related thrombosis occurred in 24 patients (6.0%). Having a peripherally inserted central catheter (PICC; HR = 3.78, 95% CI = 1.28-11.19, P = .02) compared with an implantable port and a body mass index of ⩾25.0 kg/m2 (HR = 3.60, 95% CI = 1.31-9.85, P = .01) were independently associated with increased risk of thrombosis. Central venous catheter-related thrombosis was managed mostly with removal of the catheter (19 of 24 cases) and anticoagulation, including direct-acting oral anticoagulants in 5 patients. CONCLUSIONS:This work explored rates of CVCT in a general cancer population, observing increased rates in those with PICCs or increased body mass index.

Disseminated intravascular coagulation is a complex and potentially lethal complication of malignancy, in which the fundamental abnormality is excessive activation of the coagulation system. It is a rare complication of melanoma which can be difficult to diagnose in some circumstances, leading to delay in treatment. Herein, we describe the first case of disseminated intravascular coagulation occurring in BRAF and NRAS-mutant metastatic melanoma, and systematically review the literature regarding disseminated intravascular coagulation in melanoma. This review summarizes the reported cases of disseminated intravascular coagulation in melanoma and those secondary to the novel treatment of melanoma, and explores the pathophysiology of disseminated intravascular coagulation in melanoma, highlighting the key role of expression of markers of coagulation and fibrinolysis in disseminated intravascular coagulation, as well as more widely in melanoma. Current limitations in the literature are also identified and discussed, particularly with respect to improving the management of this lethal complication. Disseminated intravascular coagulation is a rare complication of melanoma that typically portends poor prognosis.