Teresa M. Petrella

The combination of dabrafenib and trametinib is a well-established treatment for BRAF-mutated melanoma. However, the effectiveness of this approach may be hindered by the development of treatment-related pyrexia syndrome, which occurs in at least 50% of treated patients. Without appropriate intervention, pyrexia syndrome has the potential to worsen and can result in hypotension secondary to dehydration and associated organ-related complications. Furthermore, premature treatment discontinuation may result in a reduction in progression-free and overall survival. Despite existing guidance, there is still a wide variety of therapeutic approaches suggested in the literature for both the definition and management of dabrafenib and trametinib-related pyrexia. This is reflected in the practice variation of its prevention and treatment within and between Canadian cancer centres. A Canadian working group was formed and consensus statements were constructed based on evidence and finalised through a two-round modified Delphi approach. The statements led to the development of a pyrexia treatment algorithm that can easily be applied in routine practice. The Canadian working group consensus statements serve to provide practical guidance for the management of dabrafenib and trametinib-related pyrexia, hopefully leading to reduced discontinuation rates, and ultimately improve patients’ quality of life and cancer-related outcomes.

Targeted therapy has been developed through an in-depth understanding of molecular pathways involved in the pathogenesis of melanoma. Approximately ~50% of patients with melanoma have tumors that harbor a mutation of the BRAF oncogene. Certain clinical features have been identified in BRAF-mutated melanomas (primary lesions located on the trunk, diagnosed in patients BRAF mutation testing is recommended for stage III–IV melanoma, guidelines differ in recommending mutation testing in stage II melanoma patients. To fully benefit from these treatment options and avoid delays in therapy initiation, advanced melanoma patients harboring a BRAF mutation must be identified accurately and quickly. To achieve this, clear definition and implementation of BRAF reflex testing criteria/methods in melanoma should be established so that patients with advanced melanoma can arrive to their first medical oncology appointment with a known biomarker status. Reflex testing has proven effective for a variety of cancers in selecting therapies and driving other medical decisions. We overview the pathophysiology, clinical presentation of BRAF-mutated melanoma, current guidelines, and present recommendations on BRAF mutation testing. We propose that reflex BRAF testing should be performed for every melanoma patient with stages ≥IIB.

There is a global rise in skin cancer incidence, resulting in an increase in patient care needs and healthcare costs. To optimize health care planning, costs, and patient care, Ontario Health developed a provincial skin cancer plan to streamline the quality of care. We conducted a systematic review and a grey literature search to evaluate the definitions and management of skin cancer within other jurisdictions, as well as a provincial survey of skin cancer care practices, to identify care gaps. The systematic review did not identify any published comprehensive skin cancer management plans. The grey literature search revealed skin cancer plans in isolated regions of the United Kingdom (U.K.), National Institute for Health and Care Excellence (NICE) guidelines for skin cancer quality indicators and regional skin cancer biopsy clinics, and wait time guidelines in Australia and the U.K. With the input of the Ontario Cancer Advisory Committee (CAC), unique definitions for complex and non-complex skin cancers and the appropriate cancer services were created. A provincial survey of skin cancer care yielded 44 responses and demonstrated gaps in biopsy access. A skin cancer pathway map was created and a recommendation was made for regional skin cancer biopsy clinics. We have created unique definitions for complex and non-complex skin cancer and a skin cancer pathways map, which will allow for the implementation of both process and performance metrics to address identified gaps in care.

31 Background: While High-Dose Interferon (HDIFN) is the sole approved adjuvant systemic treatment for melanoma in Ontario and many other jurisdictions, it is toxic, of modest benefit, and costly. We sought to assess the population-level impact of toxicity, particularly neuro-psychiatric toxicity. This can inform value assessment for the adjuvant treatment of melanoma. Methods: This was a retrospective population-based registry study of all patients with melanoma receiving adjuvant HDIFN in Ontario 2008-2012. HDIFN receipt was determined from provincial drug-funding data. Toxicity was investigated through health services use compatible with HDIFN toxicity (e.g. mental health physician billings). Associations between early HDIFN discontinuation and health services use were examined. Using stage data reported from cancer centers on a subset of patients, propensity matched analysis compared utilization in stage IIB-IIIC patients that did and did not receive HDIFN. Results: Of 718 patients receiving HDIFN, 12% were ≥65 years, 83% had little or no comorbidity. One third had ≥1 toxicity-associated utilization within one year of starting HDIFN. 364/420 (87%) of utilization was mental health-related: 54% were family practitioner visits, 39% psychiatrist visits. Early drug discontinuation was more likely with pre-existing mental health issues in multivariable analysis (OR 2.0 (1.1,3.4)). In propensity matched analysis, HDIFN patients were more likely than untreated matched controls to have mental health utilization (51% vs. 42%, p=0.01) between 1 year pre-melanoma diagnosis to 2 years post. Conclusions: Mental health services use is common among stage IIB-IIIC patients with melanoma, especially with HDIFN. This emphasizes an important survivorship issue for these patients, and for those receiving HDIFN, and impacts the value of care. Pre-treatment mental health services use is associated with treatment discontinuation. This is important when contemplating the value of HDIFN use for individual patients. For those receiving HDIFN, optimal support must include mental health care.

E12026 Background: The 21-gene Recurrence Score (RS) assay has been shown to be both prognostic and predictive of chemotherapy (CT) benefit in patients with node negative and node positive (N+), estrogen-receptor positive (ER+) early-stage breast cancer (EBC). Currently, the assay is only reimbursed by the provincial single payer Ontario Health Ministry for node-negative EBC. Methods: The primary objective of this prospective study is to characterize how the results of the RS assay impact the decision making processes of medical oncologists in an academic centre in Ontario by evaluating recommendations for adjuvant therapy for 70 patients with ER+, HER2-negative EBC and 1-3 positive lymph nodes. Secondary objectives are to characterize changes in the physician’s level of confidence in their recommendation, to determine whether the results of the RS affect patients’ treatment preferences and their level of confidence and to evaluate the actual treatment administered. Recruitment will be completed by the time of the ASCO meeting. Here we report the results for the first 50 patients, enrolled from October 2014 to December 2015. Results: Mean patients’ age was 61 (range: 41-84). Tumor size was ≤ 2 cm in 46% of patients, > 2-5 cm in 44% and > 5cm in 10%. Tumors were grade 1 in 24% of patients, grade 2 in 50% and grade 3 in 26%. RS was low ( < 18) in 52% of cases, intermediate (RS 18-30) in 38% and high ( ≥ 31) in 10%. Treatment recommendations changed in 35% of all evaluable patients (17 out of 48). The most significant change was in the group with a low RS ( < 18), with 48% of the recommendations changing from upfront CT pre-assay, to endocrine therapy only post-assay. Physicians’ confidence in the recommendations increased in 46% of cases and decreased in 12.5%. Patients’ confidence in their treatment choice increased in 65% of cases and decreased in 13%. Upfront CT was recommended to 75% of patients pre-assay, 43% ultimately received CT. Conclusions: The RS assay resulted in a substantial decrease in the number of node positive patients who would receive CT and in an increase of the physicians’ and patients’ confidence in the adjuvant treatment recommendations.