Expert Treatment Recommendations Research Articles

Long-term medical treatment of cushing's disease with pasireotide: a review of current evidence and clinical experience.

Cushing's disease is a rare condition of chronic hypercortisolism caused by an adrenocorticotropic hormone-secreting pituitary adenoma and associated with debilitating complications and excess mortality. Transsphenoidal adenomectomy is generally first-line treatment but is contraindicated in some patients and associated with significant post-surgical recurrence. While there are few data to support long-term use of most pharmacologic treatments, pasireotide (a multireceptor-targeted somatostatin analog) recently demonstrated sustained benefit in a 12-month, multicenter, Phase III trial and in 2 long-term extension studies. The Phase III trial (N=162) demonstrated reductions in urinary free cortisol in most patients, with durable treatment effect over 12 months. Biochemical improvement was generally paralleled by reductions in Cushing's-related signs and symptoms and enhanced health-related quality of life. Long-term treatment was evaluated in 58 patients who entered a planned 12-month extension phase. Reductions in urinary free cortisol remained stable throughout the extension, with further improvements noted in clinical signs and symptoms. Similar results were reported in the smaller Phase II extension (N=18; median treatment duration, 9.7 months; range, 2 months-4.8 years). Case reports have recently emerged demonstrating sustained disease control for upto 7 years in some patients. Safety considerations for long-term medical treatment with pasireotide are generally similar to those for other somatostatin analogs, except for the incidence and severity of hyperglycemia. Most patients experience new or worsening hyperglycemia with pasireotide treatment. Expert recommendations for treatment of pasireotide-associated hyperglycemia have recently been published and new studies are planned to elucidate the optimal treatment approach for pasireotide-associated hyperglycemia.

Abstract P1-12-01: Clinical impact of internet-based tools to help guide therapeutic decisions for metastatic breast cancer (MBC)

Abstract Background: Clinical practice guidelines are an important resource to help guide management of patients with MBC. However, guidelines are sometimes difficult to apply to individual patients, particularly when there are 2 or more treatment options with similar levels of evidence. We sought to determine whether expert recommendations on MBC treatment, delivered via an interactive, online decision support tool, would change or confirm the treatment decisions of community practitioners. We further sought to analyze changes in practice patterns and expert recommendations over time by comparing data from the current tool (2013) with data from a similar tool developed previously (2012). Methods: Both online decision support tools were developed based on input from a panel of 5 experts. Each expert provided treatment recommendations for more than 400 patient scenarios based on a simplified set of variables: disease phenotype (HR status, HER2 status), previous therapy, visceral crisis (yes/no), and rate of disease progression. Users of the tool are prompted to enter specific patient criteria, and are asked to state their intended management approach for that particular patient case. The tool then shows the recommendations of the 5 MBC experts for the specific patient case that the user entered. Finally, the user is prompted to indicate whether the experts’ recommendation confirmed or changed their intended management approach. An analysis of expert recommendations and user-selected treatments was performed to compare results of the 2013 and 2012 tools. Results: The 2012 decision support tool was utilized by 697 individuals who entered more than 1000 patient case scenarios. Users indicated that the experts’ recommendations changed their intended management approach for 30% of the cases, confirmed their approach for 36%, and did not impact their intended approach for 34%. Utilization data for the 2013 tool are pending. Expert recommendations in the 2012 vs 2013 tools changed to reflect emerging developments in guidelines, evidence, and clinical practice. For example, in 2012 there was no expert consensus on use of everolimus + hormonal therapy for HR+, HER2- patient cases, whereas in 2013, everolimus-based therapy was recommended by the majority of experts (3 out of 5) for 12 different HR+, HER2- cases. There was no consensus among the experts on the use of pertuzumab + trastuzumab and a taxane for HER2+ MBC in 2012, whereas in 2013 at least 3 out of 5 experts recommended it for a total of 36 HER2+ cases. At least 3 of 5 experts recommended trastuzumab emtansine for 96 different HER2+ cases in 2013 vs 0 in 2012. In both 2012 and 2013, the greatest variability in expert treatment recommendations was observed for HR-, HER2- cases. Conclusions: An online tool providing expert advice on specific MBC patient scenarios either confirmed or changed the clinical approach for a majority of community practitioners. Decision support tools may increase the number of clinicians who make optimal treatment decisions for patients with MBC, especially when new data, agent indications, and guideline updates must be incorporated. Detailed comparisons of expert and user responses from the 2012 and 2013 decision support tools will be presented. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-12-01.

Assessing Newer Topical Treatment Options for Scalp Psoriasis

The scalp represents the most common site of involvement at the onset and throughout the course of psoriatic disease, yet it remains one of the most difficult anatomic areas to treat. Recent guidelines from the Medical Board of the National Psoriasis Foundation indicate the preeminence of topical corticosteroids in the management of scalp psoriasis while noting the benefits of various adjunctive agents, including vitamin D3 analogs and combination therapy. Although a number of topical treatment options are indicated for or have been used off-label to manage scalp psoriasis (short-contact tazarotene 0.05% or 0.1% gel, anthralin solution, keratolytics and clobetasol propionate 0.05% spray, among them), the newest agents approved by the U.S. Food and Drug Administration for the management of scalp psoriasis warrant consideration in light of these expert treatment recommendations.

Diagnosis and Treatment of Essential Thrombocythemia: Assessment of Current Clinical Practice.

Abstract 1903Poster Board I-926 Introduction:The discovery of the JAK2 V617F gene mutation has significantly altered the clinical diagnostic approach to the myeloproliferative neoplasms, reflected in the revised 2008 WHO diagnostic criteria. Both the 2001 and 2008 diagnostic criteria for essential thrombocythemia (ET) require a bone marrow biopsy showing megakaryocytic proliferation to make a diagnosis of ET. Published expert opinion based on clinical studies suggests that ET patients > 60 years old or with history of thrombosis should be characterized as high risk and treated with hydroxyurea. It is unclear whether physicians in clinical practice utilize the WHO diagnostic criteria or follow expert treatment recommendations for ET. Methods:We conducted a retrospective chart review of all patients with a clinical diagnosis of ET made by a hematologist who were seen in clinic from 2006 to 2008 at two university teaching hospitals in Vancouver, Canada. Data collected included demographic information, thrombosis history, diagnostic tests performed and treatment administered. Testing for JAK2 V617F became locally available in 2006, so for assessment of diagnostic tests performed, patients were divided into cohorts of diagnosis pre-2006 and 2006–2008. Patients were characterized as high risk if > 60 y or history of thrombosis at the time of diagnosis. All other patients were considered low risk. Results:Diagnostic information was available for 116 patients diagnosed prior to the availability of testing for JAK2 V617F. 65% (75/116) of patients in this cohort had a bone marrow biopsy performed (table 1). 44 patients received a new diagnosis of ET from 2006–2008. Only 48% (21/44) patients in this cohort had a bone marrow biopsy performed, significantly less than in the historical cohort (p = 0.019). 41/44 had JAK2 V617F testing performed: 41% (17/41) were JAK2 V617F negative, 56% (23/41) positive and 1 equivocal. Bone marrow biopsy was performed in 59% (10/17) of JAK2 V617F negative patients and 39% (9/23) of JAK2 V617F positive patients (p = 0.055) (table 1). Bone marrow biopsy was also performed in 1 patient with equivocal JAK2 V617F testing and 1 patient not tested for JAK2 V617F. 170 patients diagnosed with ET were seen in follow up 2006–2008. 64% (109/170) were high risk due to age > 60 y or history of thrombosis. The remaining 36% (61/170) were considered low risk. Hydroxyurea was used preferentially over anagrelide for treatment of ET (table 2). Only 76% of high risk patients were receiving cytoreductive treatment. 23% of low risk patients received cytoreductive treatment. ASA was prescribed to 89% of high risk and 79% of low risk patients.table 1Frequency of performing bone marrow at time of diagnosis of ETPre-20062006–20082006–2008JAK2 V617F not availJAK2 V617F NegJAK2 V617F PosTotal number of pts1161723Bone marrow performed75 (65%)10 (59%)9 (39%)table 2Treatment of ET patientsNHydroxyureaAnagrelideNo CytoreductionASAHigh risk10970 (64%)13 (12%)26 (24%)97 (89%)Low risk6112 (20%)2 (3%)47 (77%)48 (79%) Conclusion:Despite the requirement for a bone marrow biopsy to meet the WHO criteria for ET, hematologists performed a bone marrow biopsy in less than half of patients they diagnosed with ET since 2006. Hematologists performed bone marrow biopsy less frequently after JAK2 V617F testing became available, particularly in JAK2 V617F positive patients. A substantial portion of high risk patients (24%) were receiving no cytoreductive therapy, contrary to expert recommendation. Further study is required to understand the barriers to implementing treatment recommendations in clinical practice. This study highlights the challenges in translating published diagnostic criteria and treatment guidelines into changes in patient care. Disclosures:No relevant conflicts of interest to declare.