BackgroundCancer services are inaccessible in many low-income countries, and few published examples describe oncology programs within the public sector. In 2011, the Rwanda Ministry of Health (RMOH) established Butaro Cancer Center of Excellence (BCCOE) to expand cancer services nationally. In hopes of informing cancer care delivery in similar settings, we describe program-level experience implementing BCCOE, patient characteristics, and challenges encountered.MethodsButaro Cancer Center of Excellence was founded on diverse partnerships that emphasize capacity building. Services available include pathology-based diagnosis, basic imaging, chemotherapy, surgery, referral for radiotherapy, palliative care and socioeconomic access supports. Retrospective review of electronic medical records (EMR) of patients enrolled between July 1, 2012 and June 30, 2014 was conducted, supplemented by manual review of paper charts and programmatic records.ResultsIn the program’s first 2 years, 2326 patients presented for cancer-related care. Of these, 70.5 % were female, 4.3 % children, and 74.3 % on public health insurance. In the first year, 66.3 % (n = 1144) were diagnosed with cancer. Leading adult diagnoses were breast, cervical, and skin cancer. Among children, nephroblastoma, acute lymphoblastic leukemia, and Hodgkin lymphoma were predominant. As of June 30, 2013, 95 cancer patients had died. Challenges encountered include documentation gaps and staff shortages.ConclusionButaro Cancer Center of Excellence demonstrates that complex cancer care can be delivered in the most resource-constrained settings, accessible to vulnerable patients. Key attributes that have made BCCOE possible are: meaningful North–south partnerships, innovative task- and infrastructure-shifting, RMOH leadership, and an equity-driven agenda. Going forward, we will apply our experiences and lessons learned to further strengthen BCCOE, and employ the developed EMR system as a valuable platform to assess long-term clinical outcomes and improve care.

PurposeChildren with acute lymphoblastic leukemia (ALL) in low-income countries have disproportionately lower cure rates than those in high-income countries. At Butaro Cancer Center of Excellence (BCCOE), physicians treated patients with ALL with the first arm of the Hunger Protocol, a graduated-intensity method tailored for resource-limited settings. This article provides the first published outcomes, to our knowledge, of patients with ALL treated with this protocol.MethodsThis is a retrospective descriptive study of patients with ALL enrolled at BCCOE from July 1, 2012 to June 30, 2014; data were collected through December 31, 2015. Descriptive statistics were used to calculate patient demographics, disease characteristics, and outcomes; event-free survival was assessed at 2 years using the Kaplan-Meier method.ResultsForty-two consecutive patients with ALL were included. At the end of the study period, 19% (eight) were alive without evidence of relapse: three completed treatment and five were continuing treatment. Among the remaining patients, 71% (30) had died and 10% (four) were lost to follow-up. A total of 83% (25) of the deaths were disease related, 3% (one) treatment-related, and 13% (four) unclear. Event-free survival was 22% (95% CI, 11% to 36%), considering lost to follow-up as an event, and 26% (95% CI, 13% to 41%) if lost to follow-up is censored.ConclusionAs expected, relapse was the major cause of failure with this low-intensity regimen. However, toxicity was acceptably low, and BCCOE has decided to advance to intensity level 2. These results reflect the necessity of a data-driven approach and a continual improvement process to care for complex patients in resource-constrained settings.

Surgical care was provided for many cancer patients referred to BCCOE. However, challenges such as inadequate surgical infrastructure and skills, and patients presenting late with advanced and unresectable disease can limit the ability to manage all cases. This study highlights opportunities and challenges in cancer care relevant to other hospitals in rural settings.

PurposeSuccess in treating nephroblastoma in high-income countries has been transferred to some resource-constrained settings; multicenter studies report disease-free survival of greater than 70%. However, few reports present care models with rural-based components, care tasks shifted to internists and pediatricians, and data collection structured for monitoring and evaluation. Here, we report clinical outcomes and protocol compliance for patients with nephroblastoma evaluated at Butaro Cancer Center of Excellence in Rwanda.Patients and MethodsThis retrospective study reports the care of 53 patients evaluated between July 1, 2012, and June 30, 2014. Patients receiving less than half of their chemotherapy at Butaro Cancer Center of Excellence were excluded.ResultsOf the 53 patients included, 9.4% had stage I, 13.2% had stage II, 24.5% had stage III, 26.4% had stage IV, and 5.7% had stage V disease; the remaining 20.8% had unknown stage disease from inadequate work-up or unavailable surgical report. The incidence of neutropenia increased with treatment progression, and the greatest proportion of delays occurred during the surgical referral phase. At the end of the study period, 32.1% of patients (n = 17) remained alive after treatment; 24.5% (n = 13) remained alive while continuing treatment, including one patient with recurrent disease; 30.2% (n = 16) died; and 13.2% (n = 7) were lost to follow-up.ConclusionOur findings confirm that nephroblastoma can be effectively treated in resource-constrained settings. Using an approach in which chemotherapy is delivered at a rural-based center by nononcologists and data are used for routine evaluation, care can be delivered in safe, novel ways. Protocol modifications to mitigate chemotherapy toxicities and strong communication between the multidisciplinary team members will likely minimize delays and further improve outcomes in similar settings.

3627 Background: In pts with mutant FLT3 AML single agent studies with inhibitors of FLT3, such as midostaurin, yielded a high rate of peripheral blast reduction but complete and partial remissions were uncommon. One approach to overcome resistance is to combine a FLT3 inhibitor with an agent that down-regulates another leukemogenic pathway including those downstream to activated FLT3. Preclinical work has suggested that mTOR inhibitors, such as rapamycin or its analogs including everolimus, and the FLT3 inhibitor midostaurin synergistically kill mutant FLT3 dependent cell lines. Aims: To identify the maximum tolerated dose (MTD) of everolimus that can be given in combination with 50 mg orally twice daily midostaurin (established as well tolerated and capable of decreasing peripheral blast count [Fischer JCO 2010]), to determine toxicities, to observe anti-leukemic effects, to measure pharmacokinetics of each agent when administered in combination, and to observe pharmacodynamic effects including decrease in the phospho-FLT3 to total FLT3 ratio in blasts as evidence of enzyme inhibition. Methods: In this phase I study pts were treated with a combination of midostaurin at 50 mg po BID continuously beginning on day 2 and everolimus po administered on day 1 and continuously from day 8 onward. Dose escalation of everolimus was conducted according to standard 3 + 3 schema; the doses of everolimus explored were 5 mg QOD (dose level 1) and 5 mg QD (dose level 2). An additional 15 pts were enrolled at the MTD. Results: A total of 29 pts were enrolled (24 with relapsed and/or refractory AML, 4 with newly diagnosed AML considered inappropriate candidates for standard therapy, and 1 with relapsed CMML; 11 FLTwt, 14 FLT3-ITD positive, 3 FLT3 D835Y positive, 1 FLT3 D835H positive). The mean age was 66 (range 40–85) and ECOG performance statuses were 0 in 6 pts, 1 in 16 pts, and 2 in 7 pts. After 1 of 3 pts treated at the everolimus starting dose of 5 mg QOD experienced a DLT (grade 5 infection) the cohort was expanded to 6 pts; of the latter 3 pts enrolled 1 experienced a DLT of grade 3 hypoxia. The eligibility criteria were subsequently amended so as to be more stringent, including a DLCO requirement of 50% predicted. After an additional 3 evaluable pts tolerated the 5 mg QOD dose, we escalated to 5 mg QD; 3 of 4 pts treated at this dose level experienced DLT (grade 3 hypoxia, grade 3 mucositis, grade 5 soft-tissue infection), and subsequent pts were treated at the MTD, everolimus 5 mg QOD (25 pts in total received this dose). The most common drug-related toxicities at the MTD (any grade) were fatigue (40%), nausea (32%), hypertriglyceridemia (24%), vomiting (24%), hyperglycemia (20%), and elevated AST (20%). In addition to the pt who died in the first everolimus cohort, 5/25 pts discontinued due to drug-related grade 3 toxicity, including pneumonia (1), hypoxia (2), allergic reaction (1), and nausea (1). Grade 3 events that did not result in treatment discontinuation included thrombocytopenia (1), dyspnea (2), hyponatremia (1), hypokalemia (1), gum pain (1), abdominal pain (1), pneumonitis (1), and febrile neutropenia (2). One mutant FLT3 D835Y pt achieved CR and went on to allogeneic SCT. 3 pts (2 FLT3-ITD positive, 1 FLTwt) experienced a blast response (a ≥50% peripheral or bone marrow blast reduction) with 2 of these pts ultimately progressing and 1 discontinuing due to toxicity. Overall blast response or better was achieved in 4/29 pts (14%), 8 pts had stable disease, and 17 pts had progressive disease and/or received less than 15 days of therapy (6). In the 6 pts who received less than 15 days of therapy reasons for treatment termination included grade 3 (1) and grade 5 toxicity (2), progressive disease (2), and physician decision (1). The incidence of blast response or better in FLT3mut pts (4/18, 22%) was not clearly higher than that observed in other studies involving midostaurin administered at 50 mg po BID as a single agent. Pharmacokinetic and pharmacodynamic data are being analyzed, though at least one patient's blasts revealed a treatment-related decrease in the phospho FLT3/FLT3 ratio, suggesting enzyme inhibition. Conclusion: The combination of midostaurin (50 mg BID) and everolimus (5 mg QOD) is tolerable and has efficacy in AML, but it is unclear whether the addition of the rapamycin analog results in superior outcomes compared with midostaurin alone. Disclosures: Stone: Novartis: Consultancy, Research Funding. Off Label Use: evorlimus in AML. Griffin:Novartis: Consultancy, Research Funding. DeAngelo:Novartis: Consultancy.