Bintu Sherif

Quality of Life in Hormone Receptor–Positive HER-2+ Metastatic Breast Cancer Patients During Treatment with Letrozole Alone or in Combination with Lapatinib

This paper presents analyses evaluating quality of life in patients with hormone receptor–positive human epidermal growth factor receptor 2–positive tumors receiving letrozole alone or in combination with lapatinib in clinical trial EGF30008.

Meta-analysis of the association between progression-free survival and overall survival in metastatic colorectal cancer

PurposeThe validity of progression-free survival (PFS) as a surrogate endpoint for overall survival (OS) in metastatic colorectal cancer (mCRC) trials has been studied, primarily in first-line treatment. The relationship between PFS and OS has not been well studied in later lines of treatment.MethodsWe conducted a systematic literature review of mCRC phase 2 and 3 clinical trials that reported OS and PFS (or time-to-progression [TTP]) data. Correlation between endpoints (either PFS alone or PFS aggregated with TTP [PFS_TTP]) was estimated within treatment arms. Treatment effect was the ratio of the median time to OS, PFS, or PFS_TTP in the “control” versus “experimental” arm. We conducted meta-regression analyses and performed receiver-operating characteristic (ROC) analysis.ResultsWe analyzed data from 62 articles (23,527 patients). A high positive correlation was found between median PFS_TTP and median OS within treatment arms (r = 0.87; 95% confidence interval [CI], 0.82–0.91) and also between the median OS and median PFS (r = 0.89, 95% CI, 0.83–0.93)]. R2 was 0.48 for PFS_TTP and 0.59 for PFS; R2 for PFS_TTP was higher for first-line (R2 = 0.54) than second-line studies (R2 = 0.38). The ROC analysis is presented as a conceptual tool for evaluating the performance of PFS as a surrogate for OS at various thresholds.ConclusionsThe correlation of PFS, alone or aggregated with TTP, with OS in clinical trials of patients with mCRC is robust across lines of therapy and provides a useful means of predicting improvements in OS using PFS data.

Relationship Between Diclofenac Dose and Risk of Gastrointestinal and Cardiovascular Events: Meta-Regression Based on Two Systematic Literature Reviews

BACKGROUND NSAIDs are associated with risks of gastrointestinal (GI) and cardiovascular (CV) toxicities. It has been reported that the risks of GI and CV events are dose related, resulting in guidance explicitly emphasizing the use of NSAIDs at the lowest effective dose for the shortest duration. To understand the potential benefits of using lower doses of diclofenac, a more detailed understanding of the relationship of diclofenac dose and the risks of GI and CV events is required. OBJECTIVE The objective of this study was to extend previous research quantifying the NSAID dose-toxicity relationship by modeling dose as a continuous measure, allowing for an assessment of the risks of major GI and CV events for patients taking specific diclofenac doses compared with NSAID nonusers. METHODS We used studies identified in 2 recently published systematic reviews of observational studies that examined the risks of major GI and CV events associated with the use of oral NSAIDs. We developed meta-regression models, considering dose as a continuous measure, to estimate the risks of major GI and CV events for different daily doses of conventional oral diclofenac relative to nonuse of NSAIDs. RESULTS Seven of the 59 GI publications, contributing 11 dose-specific risk ratio observations, and 12 of the 51 CV studies, contributing 21 dose-specific risk ratio observations, were eligible for inclusion in the meta-regression. The models indicated positive linear relationships between diclofenac dose and the relative risks of major GI and CV events for the range of doses examined. CONCLUSIONS To our knowledge, this is the first study to quantify and aggregate the continuous relationship between the risk of GI or CV events and the dosage of an NSAID. With the recent availability of new low doses of diclofenac, the models may be used to estimate the potential reduction in risk of adverse events at these doses.

Quality-adjusted survival analysis of first-line treatment of hormone-receptor-positive HER2+ metastatic breast cancer with letrozole alone or in combination with lapatinib

Abstract Aim: Compare first-line lapatinib plus letrozole (L + Let) versus letrozole monotherapy (Let) in hormone-receptor-positive HER2 + metastatic breast cancer, employing Q-TWiST (quality-adjusted time without symptoms and toxicity) analysis to account for differences in progression times, with offsets for the impact of adverse events during the treatment period. Methods: The area under survival curves for each treatment group was partitioned into distinct health states of varying utility: toxicity (TOX), time without toxicity or disease progression (TWiST), and the period following disease progression until death or end of follow-up (REL). The utility-weighted sum of the mean health state durations was derived for each group. The threshold utility analysis evaluates how varying utility values across the states affects Q-TWiST differences between groups, although the method is limited by not varying utilities within each health state. Results: The primary analysis population was the HER2 + subgroup (n = 219). There was no significant difference between treatments in mean duration of grade 3/4 adverse events prior to progression (L + Let = 1.95 weeks; Let = 2.14 weeks; P = 0.90). Using utility weights of 0.5 for TOX and REL, L + Let was favored for quality-adjusted survival by 8.8 weeks (P = 0.09). The Q-TWiST difference between treatment groups ranged from 8 to 9.5 weeks, favoring combination therapy for all hypothetical utility levels, but none of the comparisons were statistically significant at P = 0.05. Conclusions: No significant differences were found between L + Let versus Let in mean duration of severe adverse events. Quality-adjusted survival was favored for the combination treatment arm for all utility levels examined when toxicity was defined by grade 3/4 AEs, but differences between groups were not statistically significant. Trial registration: ClinicalTrials.gov identifier: NCT00073528.

Secukinumab sustains early patient-reported outcome benefits through 1 year: Results from 2 phase III randomized placebo-controlled clinical trials comparing secukinumab with etanercept

Background Psoriasis is a chronic condition with negative impact on patients’ quality of life that most often requires lifelong effective and safe treatment. Objective This analysis focused on the effect of secukinumab treatment on patient‐reported health‐related quality of life as assessed by the Dermatology Life Quality Index (DLQI) in patients with moderate to severe psoriasis. Methods The proportion of subjects achieving DLQI score 0/1 response at week 24, time to DLQI score 0/1 response, and sustained DLQI score 0/1 response up to week 52 were compared between secukinumab and etanercept. Results Of 1470 subjects, 1144 received secukinumab and 326 received etanercept. DLQI score 0/1 response rates were significantly higher for secukinumab than for etanercept at week 24. The median time to DLQI score 0/1 response was significantly shorter for secukinumab versus etanercept (12 vs 24 weeks; P < .01). The majority of secukinumab‐treated subjects achieved DLQI score 0/1 response at week 24 and sustained it through week 52 along with a 90% to 100% reduction in the Psoriasis Area and Severity Index total score response. Limitations Placebo comparisons are limited during the maintenance period because of rerandomization at week 12. Conclusion Secukinumab treatment provided faster and greater sustained improvements in quality of life than etanercept over 52 weeks, consistent with greater clinical response.

Psoriasis patients with psoriasis Area and Severity Index (PASI) 90 response achieve greater health-related quality-of-life improvements than those with PASI 75–89 response: results from two phase 3 studies of secukinumab

Abstract Background: The emergence of new biological therapies showing high and sustained level of Psoriasis Area and Severity Index (PASI) 90 response has provided the possibility of both greater skin clearance and increased quality of life (QOL). Objective: To evaluate the association of greater response in skin clearance with improvements in skin-related QOL up to 52 weeks. Methods: Subjects achieving various levels of skin clearance (PASI 90–100 or PASI 75–89) and Dermatology Life Quality Index (DLQI) (0/1) response were compared using ERASURE and FIXTURE trial data. Similar analyses with IGA ratings of Clear or Almost Clear were performed. Results: Significantly more PASI 90–100 responders at week 12 had DLQI 0/1 response than PASI 75–89 (69.4% vs. 47.1%; p < .001) and sustained DLQI 0/1 response at week 52 (74.0% vs. 56.7%; p < .001). IGA results were similar. Conclusions: These results show that PASI 90–100 is a relevant therapeutic goal in moderate to severe psoriasis compared to PASI 75–89 when considering patients’ QOL.

NETWORK META-ANALYSIS OF RELATIVE EFFICACY AND SAFETY OF EDOXABAN VERSUS OTHER NOVEL ORAL ANTICOAGULANTS (NOACS) AMONG ATRIAL FIBRILLATION PATIENTS WITH CHADS2 SCORE ≥ 2

Notable differences in patient characteristics exist among the phase 3 trials studying non-VKA oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation. This study compared the efficacy and safety of edoxaban versus other NOACs after adjustment of baseline patient characteristics for

Longitudinal Modeling Approaches to Assess the Association Between Changes in 2 Clinical Outcome Assessments

Background: Understanding how one clinical outcome assessment (COA) (eg, a patient-reported outcome [PRO]) relates to a second COA (eg, a clinician-reported outcome [ClinRO]) may provide insights into disease burden or treatment efficacy. We aimed to briefly review commonly used cross-sectional methods to evaluate the association between a PRO and a ClinRO and to demonstrate the advantages of longitudinal modeling approaches, particularly a joint mixed model for repeated measures (MMRM), to evaluate this association. Methods: We generated an example longitudinal data set that included a PRO measured on an 11-point numeric rating scale and a binary ClinRO. The association between change in PRO score and ClinRO response at each time point was examined using 2 cross-sectional analyses: point biserial correlation and logistic regression. We conducted longitudinal analyses of the association between the 2 COAs across time points using MMRM and joint MMRM approaches. Results: Point-biserial correlation and logistic regression analyses correctly captured the “built in” associations between the 2 COAs that strengthened over time, but each association was applicable only for a single time point. The MMRM approach provided correlations over time but only for a single outcome variable. The joint MMRM approach modeled the relationship between both outcome variables simultaneously, allowing for evaluation of the correlations both within and between the variables over time. Conclusion: Each analysis demonstrated the relationship between PRO score changes and ClinRO response. Longitudinal analysis methods, particularly the joint MMRM, allow for a more thorough examination of the correlations among the 2 outcomes than cross-sectional analysis methods.

Minimal Disease Activity Among Active Psoriatic Arthritis Patients Treated With Secukinumab: 2‐Year Results From a Multicenter, Randomized, Double‐Blind, Parallel‐Group, Placebo‐Controlled Phase III Study

Objective: To evaluate minimal disease activity (MDA) among psoriatic arthritis (PsA) patients receiving secukinumab through 2 years in the FUTURE 2 study (NCT01752634). Methods: Patients with active PsA were randomized to receive subcutaneous secukinumab 300, 150, or 75 mg or placebo. MDA was assessed in the overall population (anti-tumor necrosis factor [TNF]-naïve and inadequate responders [antiTNF-IR]) and in patients stratified by prior anti-TNF exposure and by time since diagnosis at Weeks 16, 24, 52, and 104. Function, patient-reported outcomes (PROs) including health-related quality of life (QoL), and work productivity were assessed in MDA responders versus non-responders. Results: Overall, 28% (27/98) and 23% (23/100) of patients achieved MDA at Week 16 with secukinumab 300 and 150 mg, respectively, versus 10% (9/94) with placebo. In the anti–TNF-naïve cohort, a higher proportion of patients achieved MDA at Week A cc ep te d A rt ic le This article is protected by copyright. All rights reserved. 16 with secukinumab 300 and 150 mg (34% and 32%, respectively) versus placebo (13%). The corresponding value in the anti-TNF-IR cohort was 15% and 8% with secukinumab 300 and 150 mg, respectively, versus placebo (3%). At Week 16, 27.1% (16/59) of MDA responders achieved a very low disease activity (VLDA) response, with the percentage being numerically greater with secukinumab 300 and 150 mg (30% [8/27] and 26% [6/23], respectively) versus placebo (22% [2/9]). The MDA and VLDA responses with secukinumab 300 and 150 mg were sustained through 2 years. MDA responders showed greater improvements in QoL outcomes compared to non-responders through 2 years. Conclusion: A greater proportion of patients achieved MDA with secukinumab versus placebo at Week 16, with response rates sustained through 2 years. MDA was associated with improved PROs, including QoL, through 2 years.To evaluate minimal disease activity (MDA) among psoriatic arthritis (PsA) patients receiving secukinumab through 2 years in the FUTURE 2 study.