Drug Shortages in Oncology: ASCO Clinical Guidance for Alternative Treatments.

PURPOSE: To increase awareness, outline strategies, and offer clinical guidance on navigating the complexities of treatment planning amid antineoplastic drug shortages. METHODS: A multidisciplinary panel of oncologists, ethicists, and patient advocates was assembled to provide rapid clinical guidance to help providers navigate appropriate patient care in cases where rationing or alternative therapies must be considered. The groups of content experts developed general principles for resource allocation during shortages and clinical guidance on alternative therapies for specific disease sites. The recommendations are supported by evidence when available. RESULTS: A total of 44 volunteers with content expertise formed the Advisory Group that developed general guidance on the prioritization of antineoplastic agents in limited supply. Disease site-specific clinical guidance was then produced by subgroups on the basis of members' specialties and expertise. The majority of alternative treatment options were developed in consideration of cisplatin and carboplatin shortages. All guidance is posted on ASCO's website. RECOMMENDATIONS: The prioritization of antineoplastic agents in limited supply should be based on specific goals of the therapy where evidence-based medicine has shown survival outcome and life-extending benefit in both early and advanced stages. Recommendations for specific disease sites are presented. While management options vary according to the disease site, alternatives are presented. For settings in which there are no alternatives with comparable efficacy and safety, it is recommended that patients are referred to an area where the necessary drug is available or can be obtained.Additional information is available at asco.org/drug-shortages.

Gemcitabine plus enzastaurin or single-agent gemcitabine in locally advanced or metastatic pancreatic cancer: results of a phase II, randomized, noncomparative study.

PURPOSE: Gemcitabine (G) is standard therapy for pancreatic cancer. Enzastaurin (E) inhibits PKCß and PI3K/AKT signaling pathways with a dose-dependent effect on growth of pancreatic carcinoma xenografts. Data suggest that the GE combination may improve clinical outcomes. METHODS: Primary objective was overall survival (OS); secondary objectives assessed progression-free survival (PFS), response rate (RR), quality of life (QOL), toxicity, and relationships between biomarker expression and clinical outcomes. Patients were randomly assigned (2:1) to GE or G treatment; GE arm: E 500 mg p.o. daily; loading-dose (1200 mg; Day 1 Cycle 1 only) and G 1000 mg/m(2) i.v. Days 1, 8, and 15 in 28-day cycles; G arm: G as in GE. Biomarker expression was assessed by immunohistochemistry. RESULTS: Randomization totaled 130 patients (GE = 86, G = 44); 121 patients were treated (GE = 82, G = 39). GE/G median OS was 5.6/5.1 months; median PFS was 3.4/3.0 months. GE responses: 1 complete response (CR, 1.2%), 6 partial response (PR, 7.4%), and 33 stable disease (SD, 40.7%); disease control rate (DCR=CR+PR+SD, 49.4%). G responses: 2 PR (5.3%) and 16 SD (42.1%); DCR (47.4%). No QOL differences were noted between arms. GE/G Grade 3-4 toxicities included: neutropenia (18.3%/28.2%); thrombocytopenia (14.6%/25.6%); and fatigue (11.0%/7.7%). No statistically significant relationships between biomarker expression and outcomes were observed. However, patients with low expression of cytoplasmic pGSK-3ß trended toward greater OS with GE treatment. CONCLUSIONS: OS, PFS, QOL, and RR were comparable between arms. Adding E to G did not increase hematologic toxicities. GE does not warrant further investigation in unselected pancreatic cancer patients.

Secret Sauce-How Diverse Practices Succeed in Centers for Medicare & Medicaid Services Oncology Care Model.

PURPOSE: CMS' Oncology Care Model (OCM) is an episode-based alternative payment model designed to incent high-value care through the use of monthly payments for enhanced services and performance-based payments on the basis of decreases in spending compared with risk-adjusted historical benchmarks. Transitioning from a fee-for-service model to a value-based, alternative payment model in oncology can be difficult; some practices will perform better than others. We present detailed experiences of four successful OCM practices, each operating under diverse business models and in different geographic areas. METHODS: Practices that achieved success in OCM, on the basis of financial metrics, describe pathways to success. The practices represent distinct business models: a medium-sized community oncology practice, a large statewide community oncology practice, a hospital-affiliated practice, and a large academic medical center. RESULTS: Practices describe effective changes in practice culture such as new administrative flexibilities, physician champions, improved communication, changes in physician compensation, and increased physician-level transparency. New or improved clinical services include acute care clinics, care coordination, phone triage, end-of-life care programs, and adoption of treatment pathways that identify high-value drug use, including better use of supportive care drugs. CONCLUSION: There is no one thing that will ensure success in OCM. Success requires whole practice transformation, encompassing both administrative and clinical changes. Communication between administrative and clinical teams is vital, along with improved data sharing and transparency. Clinical support services must expand to manage problems and symptoms in a timely way to prevent costly emergency department visits and hospitalizations, while constant attention must be paid to making high-value therapeutic choices in both oncolytic and supportive drug categories.

A multicenter analysis of GTX chemotherapy in patients with locally advanced and metastatic pancreatic adenocarcinoma.

PURPOSE: Studies treating adenocarcinoma of the pancreas with gemcitabine alone or in combination with a doublet have demonstrated modest improvements in survival. Recent reports have suggested that using the triple-drug regimen FOLFIRINOX can substantially extend survival in patients with metastatic disease. We were interested in determining the clinical benefit of another three-drug regimen of gemcitabine, docetaxel and capecitabine (GTX) in patients with advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: The cases of 154 patients, who received treatment with GTX chemotherapy with histologically confirmed locally advanced or metastatic pancreatic adenocarcinoma, were retrospectively reviewed. All demographic and clinical data were captured including prior therapy, adverse events, treatment response and survival. RESULTS: One hundred and seventeen metastatic and 37 locally advanced cases of adenocarcinoma of the pancreas were reviewed. Partial responses were noted in 11% of cases, and stable disease was observed in 62% of patients. Responses significantly correlated with toxicity (neutropenia, ALT elevation and hospitalizations). Grade 3 or greater hematologic and non-hematologic toxicities were noted in 41% and 9% of cases, respectively. Overall median survival was 11.6 months. Chemotherapy naïve patients with metastatic and locally advanced disease achieved a median survival of 11.3 and 25.0 months, respectively. CONCLUSIONS: We observe a substantial survival benefit with GTX chemotherapy in our cohort of patients with advanced pancreatic cancer. These findings warrant further investigation of this combination in this patient population.