Dornase alfa appears to produce small but sustained improvements in lung function in patients with cystic fibrosis. It may also slow the progression of pulmonary disease. Infection rates appear to be reduced, which may well have important long-term consequences. However, evidence to date has not clarified the most appropriate use of dornase alfa in the treatment of cystic fibrosis. Whether quality of life is affected in a meaningful and measurable way is yet to be clarified. A trial of the drug in patients with cystic fibrosis who have obvious lung disease is reasonable, but continued treatment should be based on clear clinical response. Therefore, questions about the drug's exact role in the overall management of cystic fibrosis remain to be answered. Although benefits received may not prove to be cost-effective, long-term effects on disease progression may well justify use of this agent.

e14125 Background: Nivolumab and pembrolizumab, two anti-PD1 agents, were approved and funded in Québec since 2016 for non small cell lung cancer (NSCLC), renal cell carcinoma (RCC) and melanoma. The objectives were to describe and assess the “real-life” use, efficacy and security of nivolumab and pembrolizumab in NSCLC, RCC and melanoma in the general population. Methods: Medical records of every patient who received nivolumab or pembrolizumab between January 1st 2011 and October 31st 2017 were reviewed retrospectively. Data analysis cut-off was Dec 31st 2017. Results: In total, 532 patients received at least one dose of anti-PD1 during the study period. Median number of doses received varied for each indication (medians varied from 4 to 9.5). Adverse events were pooled together by drug. 47.7 % of patients receiving pembrolizumab suffered from any grade immune-related adverse event (IRAE), most of them of grade 1 or 2. 12.2 % of patients reported grade 3-4 IRAE. Most of the patients reported only one type of IRAE. For nivolumab, 44.6% of patients presented with any IRAE, including 8.3% of grade 3-4. Dermatologic IRAE were more frequent in the melanoma patients whereas gastrointestinal and pulmonary IRAE were more frequent in NSCLC patients. Treatment discontinuation due to adverse events varied from 6 to18% depending on indication. Conclusions: Nivolumab and pembrolizumab seemed less effective and caused more IRAE in “real-life” population than in the pivotal clinical trials. Caution and regular follow-up are warranted when using these drugs in general population. Longer follow-up is needed.[Table: see text]

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Background: Azacitidine (5-AZA; Vidaza®), a pyrimidine nucleoside analog, is used in the treatment of myelodysplastic syndrome (MDS) and other hematological malignancies. Pharmacy directors gave the Therapeutic Drug Management Program (TDMP - www.pgtm.qc.ca) the mandate to evaluate 5-AZA use in four University Hospitals in Quebec, Canada. Objectives: Describe and review 5-AZA use for all indications in our hospitals. Methods: A review of pharmacy databases was performed to identify patients who received 5-AZA between January 1st 2010 and May 31st 2013. Files and medical records of every patient who received 5-AZA during the study period were reviewed to assess diagnostic (including International Prognostic Scoring System (IPSS) scores), treatment, response and non-hematological adverse events. Results: A total of 77 patients received 5-AZA during the study period, 56 (72.7 %) for the treatment of MDS, 15 (19.5 %) for acute myeloid leukemia (AML) and 6 (7.8 %) for chronic myelomonocytic leukemia (CMML). At the end of the study period, 31 patients were alive (14 were still on treatment), 35 patients had died and 11 were lost to follow up. Excluding the 14 patients still on treatment, 32 patients (50.8 %) received at least 6 cycles of 5-AZA. In the MDS population (76.7 % with an intermediate-2 or higher IPSS score), patients received a mean of 8.0 cycles (median = 6) and the overall benefit rate (OBR) (complete remission, partial remission, hematological improvement or stable disease) was 48.2 %. The median overall survival (OS) was 17.8 months and the median time to progression (TTP) was 9.7 months. MDS transformation to AML occurred in 16 patients after a mean of 9.9 months. Median time to transformation or death in the MDS population was 14.4 months. In the AML population, patients received a mean of 6.6 cycles (median = 5) and the OBR was 26.7 %. The median OS was 12.2 months and the median TTP was 6.5 months. In the CMML population, patients received a mean of 10 cycles (median = 5.5) and the OBR was 50% (3 of the 6 patients achieved stable disease). Across all patient populations, a 5-AZA dose of 75 mg/m2 for 7 days every 28 days was used in 77.8% of patients. Non-hematological adverse events were seen in 67 patients (87 %) but were mostly mild and most did not lead to delays or dose reductions (treatment intensity of 96 %). Conclusions: Our results show that 5-AZA had a more limited benefit in our real-life population when compared to published clinical trials (OBR of 44.2 % in MDS, AML and CMML populations combined compared to 60% and 61% and a mean exposition of 8.1 months compared to 10.3 to 11.4 months in the pivotal clinical studies (AZA-001 and CALGB 9221 respectively)). Considering that 5-AZA is often the only treatment we can offer these patients and considering its high cost, it would be of highest importance to wisely choose patients to whom we offer this treatment and to periodically re-evaluate its use (at least after the 6th cycle) to confirm the patient is benefiting from treatment. Disclosures Olney: Cellgene: Honoraria; Pfizer: Consultancy; BMS: Consultancy; Novartis: Consultancy.