EOSTA: An Observational Study on the Compliance and Quality of Life (QoL) of Chronic Myeloid Leukemia (CML) Patients Treated with Second Line Nilotinib (Tasigna®)^: Interim Results At 6 Months of Follow-up,

Nilotinib, a second generation tyrosine kinase inhibitor, is indicated in Ph+ chronic or accelerated phase-CML patients with imatinib-resistance or -intolerance. A 400mg BID schedule is recommended for this indication, with doses taken approximately 12 hours apart, outside meal times. No food should be consumed for 2 hours before and at least 1 hour after dose intake. Such recommendations may affect the compliance to nilotinib treatment, a critical factor for therapeutic success.

The primary objective of EOSTA was to evaluate the compliance rate to nilotinib using the Morisky score, after 12 months of follow-up (FU). The other objectives were to describe the changes in compliance over a 12 months period, factors associated with non-compliance, and changes in QoL of patients treated with nilotinib. Data recorded by physicians and patients are summarized in Table 1.

Here are presented the results based on the interim analysis of the whole population at 6 months of FU. From November 2008 to September 2010, 145 patients were included in 30 sites in France. At the last time of analysis, 87 patients (60%) had a Morisky score documented at 6 months and could be analyzed for compliance.

Forty four out of 87 (50,6%) patients were males, the median age was 57.5 years (24 to 83), 42% had a professional activity and 45% were retired. At inclusion, 77 patients were already treated with nilotinib (47 for less than 1 year, 30 for more than 1 year) and 67% of the patients received nilotinib 800 mg daily (mean 671 mg). The mean daily dose of nilotinib at 6 months was 680 mg, comparable to that at inclusion. Previous therapies included imatinib in all cases (57.5% resistant), 22% have been previously treated with dasatinib and 24 % of patients were taking more than 3 concomitant long-term medications in addition to TKI.

According to Morisky score rated at 6 months, compliance was high (Morisky score ≥3) in 87% of the patients and was stable over 6 months. Occasional missing dose was declared by 28% of patients. Compliance was high in all patients ≥ 60 years old, retired and receiving more than 3 long term concomitant treatments, in 64% of patients less than 40 years, 83% of active patients, and 82% of patients receiving up to 3 concomitant treatments.

In a separate questionnaire, occasional missed dose were reported in 45% of patients, one day a week maximum in 81% of them, mainly because of forgetting (40%) and inadequate timing (26%). Interestingly 80% of patients declared not to be disturbed by nilotinib modalities of administration.

According to the QoL questionnaire EQ-5D, EVA (self-rated health index) was stable over the first 6 months of FU (mean 70.6 to 70.3). Autonomy was not impacted, few issues (roughly 25% of patients) were notified in terms of mobility, usual activities, and some problems of pain/discomfort and anxiety/depression were notified in respectively 62% and 43% of patients.

QLQ-C30 scores were analyzed, showing good global health status (mean 69, 33 to 100), good functional score (mean 80, 37 to 100), and poor symptom score (mean 20, 0 to 85). These results were stable over time since inclusion regardless of duration of previous nilotinib treatment.

At least one adverse event (AE) was reported in 29% of patients and a serious AE in 5%. They were mainly grade I/II. No grade IV was reported. The most frequent AEs were cutaneous (8.3%), gastrointestinal (6.9%) and musculoskeletal (6.2%) disorders.

Based on preliminary results at 6 months, reflecting nilotinib use in the real life in CML patients with resistance or intolerance to imatinib, compliance to treatment was favourable especially in patients treated for less than one year and elderly patients. Overall, QoL was not impaired despite some issues on mobility, usual activities, pain/discomfort and anxiety/depression. The safety profile was favourable. These results need to be confirmed on the final analysis planned at 12 months of FU. Updated results will be presented.

Rea:Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Maloisel:BMS: Honoraria; Novartis: Membership on an entity's Board of Directors or advisory committees. Huguet:BMS: Honoraria; Novartis: Membership on an entity's Board of Directors or advisory committees. Okada:Novartis: Employment. Bourdeix:Novartis: Employment. Nicolini:Bristol Myers Squibb France: Consultancy, Speakers Bureau; Norvartis Pharma France: Consultancy, Research Funding, Speakers Bureau. Tulliez:Novartis: Honoraria; BMS: Honoraria. Etienne:consultant for Novartis Pharma France and Bristol Myers Squibb: Consultancy.