Novel application of Kaplan-Meier methods to model tolerance for nonadherence to imatinib in patients with chronic myeloid leukemia (CML) in the ADAGIO study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7038-7038
Author(s):  
Mavis Obeng-Kusi ◽  
Karen MacDonald ◽  
Marie-Anne van Lierde ◽  
Ivo Abraham
Keyword(s):  
Treatment Response ◽  
Myeloid Leukemia ◽  
Patient Adherence ◽  
Time Variable ◽  
Pill Count ◽  
Imatinib Treatment ◽  
Post Hoc Analysis ◽  
Kaplan Meier ◽  
Treatment Responses ◽  
Post Hoc

7038 Background: Although adherence to imatinib treatment has been shown to be critical for attaining treatment response among patients with CML, some studies have suggested a 7.3-9.9% nonadherence tolerance margin before loss of treatment effects. We aimed to model probabilistically the margin of tolerance required to ensure treatment response among patients prescribed imatinib and the margin, if any, before treatment response is at risk. Methods: We performed a post hoc analysis of the ADAGIO study conducted in Belgium on 169 evaluable patients ( Blood 2009). Using the pill count ratio as, what in conventional survival analysis would be, the time variable, we modeled the cumulative likelihood of treatment response as a function of increasing pill count adherence. We applied Kaplan-Meier methods to model the likelihood of complete cytogenetic (CCyR), complete hematological (CHR), major molecular (MMR) and optimal (OR) (as defined by the European Leukemia Net) response as a function of 90-day pill count adherence. Kaplan-Meier methods thus estimated the tolerance for nonadherence to imatinib by calculating the 1 minus Kaplan-Meier estimate for treatment response. Results: Analyses (see Table) showed that ̃100% adherence of prescribed dose is associated with probabilities (rounded) 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. (of 0.7698 (MMR). Increasing the intake of imatinib from 90% to 100% of the prescribed dose increased the likelihood of the various treatment responses by 1.95 to 2.35-fold. Conclusions: Our findings challenge any previously estimated tolerance for nonadherence. There is virtually no margin for nonadherence if the objective is to optimize the likelihood of treatment response, and only a minimal margin to avoid impaired treatment response. Under such adherence, response rates similar to those in the pivotal IRIS trial can be obtained. Clinicians must assess and promote patient adherence, and patients must be perfectly adherent.[Table: see text]

Patient Nonadherence and Treatment Response to Imatinib in Patients with Chronic Myeloid Leukemia: Results from the ADAGIO Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2379-2379
Author(s):  
Lucien Noens ◽  
Marie-Anne van Lierde ◽  
Robrecht De Bock ◽  
Gregor Verhoef ◽  
Pierre Zachee ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Treatment Response ◽  
Myeloid Leukemia ◽  
Pill Count ◽  
Molecular Response ◽  
Imatinib Treatment ◽  
Major Molecular Response ◽  
Adherence Behavior ◽  
Long Term Treatment ◽  
Patient Nonadherence

Abstract BACKGROUND. Imatinib therapy for chronic myeloid leukemia (CML) is a long-term treatment potentially compromised by patient nonadherence. OBJECTIVE. To examine whether patients (pts) at different levels of treatment response differ in adherence to imatinib treatment. DESIGN & PATIENTS. The ADAGIO study1 is a prospective, 90-day (90d) observational, open-label, multicenter study of pts with chronic myeloid leukemia (CML) and treated with imatinib. 169 evaluable pts who had been on imatinib for a minimum 30 days at enrollment were studied. A sub-analysis included pts with optimal vs. suboptimal response (all patients) and complete vs. incomplete cytogenetic response (CgR; all patients and those treated with imatinib ≥12 months). MEASUREMENTS. Adherence: imatinib pill count over 90d expressed as % of prescribed imatinib taken. Suboptimal response (SR): incomplete hematologic response at 3 months, and/or less than partial CgR at 6 months, and/or less than major molecular response and, in case of loss of major molecular response, other limitations or chromosomal abnormalities at 18 months (all else: optimal response [OR]). CgR: complete (0% Ph+ metaphases) or incomplete (≥1 Ph+ metaphases). RESULTS. Pill count percentages ranged from 29%–202% of prescribed dose (M=90.9±20.1). Pts with SR (n=14) had significantly higher %s of imatinib not taken (23.2±23.8) than did those with OR (n=124; 7.3±19.3, P=0.005). Among pts treated with imatinib ≥12 months, those with complete CgR (n=98) had significantly lower mean percentages of imatinib not taken (9.0±18.6) than those with incomplete CgR (n=9; 26.0±24.4, P=0.012). Among all patients regardless of length of treatment, those with complete CgR (n=109) also had significantly lower mean percentages of drug not taken (9.1±18.1) than those with incomplete CgR (n=19; 23.9±19.2, P=0.004). CONCLUSIONS. Proportions of CML patients with poor treatment response are low (10.1%, 8.4%, and 14.8% resp. for parameters above), underscoring the high efficacy of imatinib in CML. Pts with poor response tended to have higher % of imatinib not taken over 90d, an index of overall adherence behavior. Clinicians should be aware of the association between adherence and imatinib response and should query patients about their adherence behavior. Nonadherence should be ruled out prior to classifying a patient as imatinib-resistant. Enhanced adherence is likely to optimize the effectiveness of imatinib treatment in CML.

scholarly journals Outcomes After Drug-Coated Balloon Treatment of Femoropopliteal Lesions in Patients With Critical Limb Ischemia: A Post Hoc Analysis From the IN.PACT Global Study

2019 ◽  
Vol 26 (3) ◽  
pp. 305-315 ◽  
Author(s):  
Michel M. P. J. Reijnen ◽  
Iris van Wijck ◽  
Thomas Zeller ◽  
Antonio Micari ◽  
Pierfrancesco Veroux ◽  
...  
Keyword(s):  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Target Lesion ◽  
Major Amputation ◽  
Limb Amputation ◽  
Post Hoc Analysis ◽  
Kaplan Meier ◽  
Global Study ◽  
Post Hoc ◽  
Drug Coated Balloon

Purpose: To report a post hoc analysis performed to evaluate 1-year safety and efficacy of the IN.PACT Admiral drug-coated balloon (DCB) for the treatment of femoropopliteal lesions in subjects with critical limb ischemia (CLI) enrolled in the IN.PACT Global study ( ClinicalTrials.gov identifier NCT01609296). Materials and Methods: Of 1535 subjects enrolled in the study, 156 participants (mean age 71.8±10.4; 87 men) with CLI (Rutherford categories 4,5) were treated with DCB angioplasty in 194 femoropopliteal lesions. This cohort was compared to the 1246 subjects (mean age 68.2±10.0 years; 864 men) with intermittent claudication (IC) treated for 1573 lesions. The CLI cohort had longer lesions (13.9±10.6 vs 11.9±9.4 cm, p=0.009) and a higher calcification rate (76.8% vs 67.7%, p=0.011). Major adverse events [MAE; composite of all-cause mortality, clinically-driven target lesion revascularization (CD-TLR), major (above-ankle) target limb amputation, and thrombosis at the target lesion site], lesion and vessel revascularization rates, and EuroQol-5D were assessed through 1 year. The Kaplan-Meier method was used to estimate survival, CD-TLR, and amputation events; estimates are presented with the 95% confidence intervals (CI). Results: Estimates of 12-month freedom from major target limb amputation were 98.6% (95% CI 96.7% to 100.0%) in subjects with CLI and 99.9% (95% CI 99.8% to 100.0%) in subjects with IC (p=0.002). Freedom from CD-TLR through 12 months was 86.3% (95% CI 80.6% to 91.9%) in CLI subjects and 93.4% (95% CI 91.9% to 94.8%) in IC subjects (p<0.001). The MAE rate through 12 months was higher in CLI subjects (22.5% vs 10.7%, p<0.001), and CLI patients had poorer overall survival (93.0%, 95% CI 88.9% to 97.2%) than IC subjects (97.0%, 95% CI 96.0% to 97.9%, p=0.011). Health status significantly improved in all domains at 6 and 12 months in both groups. Conclusion: Treatment of femoropopliteal disease with DCB in CLI patients is safe through 12-month follow-up, with a low major amputation rate of 1.4%. The rates of MAE and CD-TLR were higher in CLI subjects and reinterventions were required sooner. Additional research is needed to evaluate long-term outcomes of DCB treatment for femoropopliteal lesions in CLI patients.

Real-world study of imatinib treatment patterns and outcomes among veteran patients with chronic myeloid leukemia.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6600-6600
Author(s):  
Lizheng Shi ◽  
Lei Chen ◽  
Hari Sharma ◽  
Maryna Marynchenko ◽  
Eric Q. Wu ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Disease Progression ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Treatment Patterns ◽  
Imatinib Treatment ◽  
Dose Increase ◽  
First Line Therapy ◽  
Diagnosis Codes ◽  
Kaplan Meier

6600 Background: Imatinib (IM) is the most commonly used drug in the treatment of chronic myeloid leukemia-chronic phase (CML-CP) patients (pts). This study investigated the treatment patterns and outcomes for veteran CML-CP pts initiated on IM. Methods: Pts (age >18 yrs) with >1 CML diagnosis codes documented (ICD-9 CM: 205.1x) between 1/1/2000 and 12/31/2010 were identified from the VISN 16 data warehouse. Pts were required to have initiated IM as the first-line therapy in CML-CP. Accelerated and blastic phases (A/BP) were identified based on WHO classification using CBC information. IM dose adjustments were assessed as dose increase from <400 mg to >600mg or from 400-600mg to >800 mg daily. Rates of IM discontinuation (no use of IM for >60 days) and switching to other drug therapy (dasatinib/nilotinib (DS/NL), hydroxyurea, and interferon-alpha) were estimated. Time to discontinuation, progression to A/BP, and survival were assessed using Kaplan-Meier analysis (K-M). Overall survival was measured from IM initiation while survival among pts with disease progression was measured from the date of progression. Results: Among the 137 pts selected, average age was 64.8 yrs and follow-up time was 4.0 yrs. 16.8% of pts had dose increase from <400mg to >600mg and 21.7% of these pts switched to other therapy after dose increase. 13.1% of pts had dose increase from 400-600mg to >800 mg with 22.2% of these pts switching to other therapy later. During the study, 83.8% of the 74 pts who discontinued IM did not use other drug therapies; and 16.2% (12 pts) switched, among which 9 pts took DS/NL. K-M showed that 25.6% and 42.4% pts discontinued IM treatment by year 1 and 2 and 8.1% and 16.0% pts experienced disease progression by year 1 and 2, respectively. Among the 28 patients who had disease progression, 32.1% continued IM use after progression and only 7.1% switched to other therapies (50% switching to DS/NL). The mortality rates were 3.0% and 9.5% by year 1 and 2 after IM initiation, and 21.7% and 42.7% by year 1 and 2 after disease progression, respectively. Conclusions: The majority of IM-treated patients, including patients with disease progression, discontinued IM use without switching to other effective therapies.

scholarly journals P.005 Long-term retention on adjunctive brivaracetam in adults with focal seizures and previous carbamazepine, lamotrigine, levetiracetam, or topiramate use: Post-hoc analysis

2019 ◽  
Vol 46 (s1) ◽  
pp. S14-S15
Author(s):  
K Foris ◽  
M Martin ◽  
S Dimova ◽  
S Elmoufti ◽  
C Laloyaux ◽  
...  
Keyword(s):  
Retention Rates ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Post Hoc Analysis ◽  
Focal Seizures ◽  
Term Retention ◽  
Kaplan Meier ◽  
Long Term Retention ◽  
Post Hoc

Background: Previous post-hoc analysis of three 12-week, double-blind, placebo-controlled trials of adjunctive brivaracetam (BRV) in patients with focal seizures demonstrated similar efficacy over placebo regardless of previous carbamazepine (CBZ), lamotrigine (LTG), levetiracetam (LEV), or topiramate (TPM) failure. This analysis explored long-term retention of adjunctive BRV in patients with previous CBZ/LTG/LEV/TPM. Methods: Post-hoc analysis of double-blind, placebo-controlled trial (N01358 [NCT01261325]) and open-label extension (N01379 [NCT01339559]; cut-off 15-March-2017) of adjunctive BRV in patients (≥16 years) with focal seizures. Outcomes were assessed in patients randomized to BRV (100 or 200 mg/day) who had previous CBZ/LTG/LEV/TPM (stopped ≥90 days before BRV initiation). Results: 503 patients were analyzed. Baseline characteristics were generally similar in subgroups with previous CBZ/LTG/LEV/TPM (n=209/162/256/182). Overall, Kaplan-Meier-estimated BRV retention at 1-, 3-, and 5-years was 71.0%, 50.9%, and 32.4%. Across previous antiepileptic drug (AED) subgroups, Kaplan-Meier-estimated BRV retention (1-year: 64.8%–73.2%; 3-year: 41.9%–49.9%; 5-year: 31.5%–35.7%), BRV discontinuations (58.4%–63.0%), and most common reasons for discontinuation (lack of efficacy: 23.0%–25.3%; adverse event: 16.7%–22.2%) were generally similar. Conclusions: Post-hoc analysis demonstrated similar long-term retention rates and discontinuation reasons with adjunctive BRV in adults previously treated with CBZ/LTG/LEV/TPM. Adjunctive BRV provides long-term effectiveness in patients who failed common AED treatments, including LEV.UCB Pharma-sponsored

scholarly journals The relationship between the reporting of euphoria events and early treatment responses to pregabalin: an exploratory post-hoc analysis

2019 ◽  
Vol Volume 12 ◽  
pp. 2577-2587 ◽  
Author(s):  
Bruce Parsons ◽  
Rainer Freynhagen ◽  
Stephan Schug ◽  
Ed Whalen ◽  
Marie Ortiz ◽  
...  
Keyword(s):  
Early Treatment ◽  
Post Hoc Analysis ◽  
Treatment Responses ◽  
Post Hoc ◽  
The Relationship

Toxicity and efficacy of bolus (BOL) versus continuous intravenous (CIV) dosing of doxorubicin (DOX) in soft tissue sarcoma (STS): Post hoc analysis of a prospective randomized trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11023-11023
Author(s):  
Lee D. Cranmer ◽  
Yao Lu ◽  
Karla V. Ballman ◽  
Elizabeth Trice Loggers ◽  
Seth Pollack
Keyword(s):  
Randomized Trial ◽  
Proportional Hazards ◽  
Performance Status ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Post Hoc Analysis ◽  
Kaplan Meier ◽  
Grade 3 ◽  
Post Hoc

11023 Background: DOX remains critical in STS treatment. Controversy exists regarding its optimal administration route (BOL vs CIV). BOL vs CIV could affect toxicity and/or efficacy. A randomized trial to assess this is unlikely. We conducted a post hoc analysis to explore differences in these routes of DOX administration. Methods: Data from a prospective randomized phase III study of doxorubicin with or without evofosfamide (TH-302) were used. At the discretion of treating physician, BOL or CIV DOX could be used. Grade 3-5 hematologic, non-hematologic and cardiac toxicities and treatment response were explored using multivariable logistic regression. OS and PFS were analyzed using Kaplan-Meier and Cox proportional hazards. Results: 640 subjects were enrolled (556 BOL, 84 CIV). Baseline differences in age, extent of disease and prior radiotherapy were controlled for in regression models. Hematologic toxicity was associated with age, performance status (PS) and cumulative (CUM) DOX dose. Non-hematologic toxicity was associated with age, PS, receipt of prior radiotherapy and CUM TH-302 dose. Cardiac toxicity was only associated with CUM DOX dose. Odds of response were strongly associated with CUM DOX dose (mg/m2, OR = 1.011, p < 0.0001), and, to a lesser extent, with CUM TH-302 dose (g/m2, OR = 1.081, p = 0.0008), STS subtype and prior radiotherapy. Comparing CIV to BOL DOX, neither OS (median 21.7m vs 18.3m, HR = 0.85, p = 0.29) nor PFS (median 6.1m vs. 6.1m, HR = 0.89, p = 0.43) was affected by manner of DOX administration (CIV vs BOL). Cox analyses indicated that factors reflecting tumoral biology and host status, rather than treatment received, were associated with OS (PS, histologic STS subtype, histologic grade, receipt of prior radiotherapy) and PFS (PS, treatment-related toxicity). Conclusions: Our analyses provide no evidence for superiority of either BOL or CIV administration of DOX as regards toxicity or efficacy in STS treatment. Thus, the logistically simpler BOL administration of DOX should be favored over CIV administration.

Sign in / Sign up

Export Citation Format

Share Document