Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study.

Imatinib mesylate (imatinib) has been shown to be highly efficacious in the treatment of chronic myeloid leukemia (CML). Continuous and adequate dosing is essential for optimal outcomes and with imatinib treatment possibly being lifelong, patient adherence is critical. The ADAGIO (Adherence Assessment with Glivec: Indicators and Outcomes) study aimed to assess prospectively over a 90-day period the prevalence of imatinib nonadherence in patients with CML; to develop a multivariate canonical correlation model of how various determinants may be associated with various measures of nonadherence; and to examine whether treatment response is associated with adherence levels. A total of 202 patients were recruited from 34 centers in Belgium, of whom 169 were evaluable. One-third of patients were considered to be nonadherent. Only 14.2% of patients were perfectly adherent with 100% of prescribed imatinib taken. On average, patients with suboptimal response had significantly higher mean percentages of imatinib not taken (23.2%, standard deviation [SD] = 23.8) than did those with optimal response (7.3%, SD = 19.3, P = .005; percentages calculated as proportions x 100). Nonadherence is more prevalent than patients, physicians, and family members believe it is, and therefore should be assessed routinely. It is associated with poorer response to imatinib. Several determinants may serve as alert signals, many of which are clinically modifiable.

No margin for non-adherence: Probabilistic kaplan-meier modeling of imatinib non-adherence and treatment response in CML (ADAGIO study).

BACKGROUND: Although adherence to imatinib is critical for attaining treatment responses in chronic myeloid leukemia, there is evidence of varying adherence among patients. Our aim was to model and determine the margin of tolerance, if any, required to ensure treatment responses among patients prescribed imatinib before treatment response is at risk. METHOD: We performed post hoc analyses of the ADAGIO study conducted in Belgium on 169 evaluable patients (Blood 2009). Applying Kaplan-Meier methods using adherence instead of the conventional time variable, we modeled the likelihood of complete cytogenetic (CCyR), complete hematological (CHR), major molecular (MMR) and optimal (OR) response as a function of 90-day pill count adherence. RESULTS: Analyses showed that ∼100 % adherence of prescribed dose is associated with probabilities of 0.84 for CHR, 0.83 for CCyR, 0.82 for OR, and 0.77 for MMR; compared to, 0.37 (CHR and CCyR), 0.35 (OR), and 0.39 (MMR) at 90 % adherence. Increasing intake of imatinib from 90 % to 100 % of the prescribed dose increased the likelihood of the various treatment responses by 1.95-2.35-fold. CONCLUSION: There is virtually no margin for nonadherence, if the objective is to optimize the likelihood of treatment response, and a minimal margin to avoid impaired treatment response.

Nonadherence to imatinib treatment in patients with gastrointestinal stromal tumors: the ADAGIO study.

AIM: To determine imatinib nonadherence rates in patients with gastrointestinal tumors (GIST) over 90 days. PATIENTS AND METHODS: A prospective 90-day observational, open-label, multicenter study was carried out of 28 evaluable GIST patients on imatinib. Nonadherence behavior was measured using a 4-item patient interview. Clinicians, patients, and collaterals rated perceived patient adherence on a 0-100 VAS scale. RESULTS: Nonadherence rates in the 4 weeks prior to baseline and follow-up were 29% (95% CI=26-32) and 24% (95% CI=21-27, p>0.05). Mean VAS ratings of perceived adherence ranged from 95.2 ± 10.2 to 97.3 ± 4.8 (p>0.05 for time and source of rating). Correlations between perceptions of and actual adherence behavior were negative. CONCLUSION: In this first study on imatinib nonadherence in GIST patients, rates were similar to those observed in patients with chronic myeloid leukemia, higher than clinically expected and exceeding meta-analytic estimates for cancer. Nonadherence rates were consistent across the 90-day period. Nonadherence behavior should be assessed by clinicians.

Imatinib for the treatment of patients with unresectable or metastatic malignant KIT-positive gastrointestinal stromal tumours: an open-label Belgian trial.

BACKGROUND: Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the gastrointestinal tract. They are defined immunohistologically as KIT positive tumours. The only effective treatment for malignant GIST was surgery until 2000. Imatinib mesylate (STI571, Glivec) has shown substantial anticancer activity in patients with metastatic or unresectable GIST. PATIENTS AND METHODS: 57 patients who were diagnosed with unresectable or metastatic malignant GIST were entered into this study. The patients were given 400 mg Glivec orally once daily. The dose could be increased to 600 mg orally once daily and then to 400 mg twice daily if tumour progression was noticed. Daily treatment was interrupted or dose was decreased only in the case of limiting toxicities. We evaluated the tumour response and the safety of the drug. RESULTS: 85% of GIST patients showed a partial response or stable disease after 8 weeks of treatment with imatinib. The main side effects were nausea, vomiting, anorexia, skin rash, periorbital oedema and diarrhea. CONCLUSION: This study confirms that imatinib is an active agent against malignant GIST with manageable toxicities.