A COMPARISON OF KAPLAN-MEIER AND CUMULATIVE INCIDENCE ESTIMATE IN THE PRESENCE OR ABSENCE OF COMPETING RISKS IN BREAST CANCER DATA

Statistical techniques such as Kaplan-Meier estimate is commonly used and interpreted as the probability of failure in time-to-event data. When used on biomedical survival data, patients who fail from unrelated or other causes (competing events) are often treated as censored observations. This paper reviews and compares two methods of estimating cumulative probability of cause-specific events in the present of other competing events: 1 minus Kaplan-Meier and cumulative incidence estimators. A subset of a breast cancer data with three competing events: recurrence, second primary cancers, and death, was used to illustrate the different estimates given by 1 minus Kaplan-Meier and cumulative incidence function. Recurrence of breast cancer was the event of interest and second primary cancers and deaths were competing risks.The results indicate that the cumulative incidences gives an appropriate estimates and 1 minus Kaplan-Meier overestimates the cumulative probability of cause-specific failure in the presence of competing events. In absence of competing events, the 1 minus Kaplan-Meier approach yields identical estimates as the cumulative incidence function.The public health relevance of this paper is to help researchers understand that competing events affect the cumulative probability of cause-specific events. Researchers should use methods such as the cumulative incidence function to correctly estimate and compare the cause-specific cumulative probabilities

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

Systematic review and network meta-analysis of the relative efficacy and safety of edoxaban versus other nonvitamin K antagonist oral anticoagulants among patients with nonvalvular atrial fibrillation and CHADS score ⩾ 2

Background: The nonvitamin K antagonist oral anticoagulants pivotal clinical trials for stroke prevention in atrial fibrillation have important differences in trial designs and baseline patient characteristics. Objective: We sought to evaluate the relative efficacy and safety of edoxaban versus other nonvitamin K antagonist oral anticoagulants in the management of stroke prevention in atrial fibrillation by adjusting for differences in baseline stroke risk and the length of follow-up among the four phase 3 randomized controlled trials. Methods: We conducted a systematic literature review of randomized controlled trials evaluating the nonvitamin K antagonist oral anticoagulants for stroke prevention in atrial fibrillation and performed a network meta-analysis using data from ENGAGE AF-TIMI 48, RE-LY, ROCKET-AF, and ARISTOTLE, with warfarin as a common comparator. To adjust for between-trial differences in CHADS 2 score and length of follow-up, annualized event rates among patients with CHADS 2 score ⩾ 2 were analyzed using a mixed Poisson’s regression model. Results: Once-daily high-dose edoxaban was associated with significant lower major bleeding episodes compared with once-daily rivaroxaban (risk ratio, 0.76; 95% confidence interval, 0.66–0.89), twice-daily dabigatran 150 mg (risk ratio, 0.78; 95% confidence interval, 0.61–0.84), and twice-daily dabigatran 110 mg (risk ratio, 0.83; 95% confidence interval, 0.71–0.98) and similar bleeding risk compared with twice-daily apixaban (risk ratio, 1.08; 95% confidence interval, 0.91–1.28). Risk of stroke and systemic embolism was similar for the high-dose edoxaban and other nonvitamin K antagonist oral anticoagulant regimens. The low-dose edoxaban regimen was associated with a significant lower risk of major bleeding than other nonvitamin K antagonist oral anticoagulants and a significant higher risk of stroke and systemic embolism compared with apixaban and dabigatran 150 mg. Conclusion: Among patients with atrial fibrillation and CHADS 2 score ⩾ 2, the high-dose edoxaban regimen may offer similar efficacy to the other nonvitamin K antagonist oral anticoagulants but with a significant major bleeding benefit over rivaroxaban and dabigatran

Minimal Disease Activity among Active Psoriatic Arthritis Patients Treated with Secukinumab: 2-year Results from the FUTURE 2 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 [anti-TNF-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 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. This article is protected by copyright. All rights reserved

Achievement of remission endpoints with secukinumab over 3 years in active ankylosing spondylitis : pooled analysis of two phase 3 studies

Introduction Clinical remission in patients with ankylosing spondylitis (AS) has been determined using composite indices such as the AS Disease Activity Score inactive disease (ASDAS-ID), Assessment of SpondyloArthritis international Society criteria partial remission (ASAS-PR), and low Bath AS Disease Activity Index (BASDAI) scores. The objective of this exploratory analysis was to evaluate the proportion of secukinumab-treated patients with AS achieving remission defined based on the ASDAS-ID (score < 1.3), ASAS-PR or BASDAI score <= 2. Methods The analysis pooled data from the MEASURE 1 and 2 studies over 3 years. The proportion of patients who achieved ASDAS-ID, ASAS-PR, or BASDAI <= 2 with secukinumab was compared with placebo at week 16; results for secukinumab-treated patients were summarized through week 156. Sustainability of each criterion was assessed from week 16 to 156 using shift analysis. The association between each of these criteria and specific patient-reported outcomes (PROs), such as health-related quality of life, function, fatigue, and work impairment, was also explored. Results At week 16, a higher proportion of secukinumab-treated patients versus placebo achieved ASDAS-ID (17.6 vs. 3.5%), ASAS-PR (15.4 vs. 4.1%), or BASDAI <= 2 (22.3 vs. 6.4%) criteria (all P < 0.0001), which were sustained through 156 weeks. Shift analysis showed that the majority of secukinumab-treated patients achieving remission at week 16 maintained their status at week 156 (ASDAS-ID, 57.1%; ASAS-PR, 68.0% and BASDAI <= 2, 74.3%). Remission was also associated with improved PROs over 156 weeks. Conclusions Secukinumab-treated patients maintained ASDAS-ID, ASAS-PR, or BASDAI <= 2 from week 16 up to 3 years. Patients who achieved at least one of the three responses/states, reported improvement in PROs, which suggests an association of clinical remission/ID with PROs in patients with active AS

Effect of Secukinumab on Quality of Life and Psoriasis-Related Symptoms: A Comparative Analysis Versus Ustekinumab from the CLEAR 52-Week Study

BACKGROUND: Secukinumab has demonstrated greater sustained skin clearance than ustekinumab through week 52, greater improvement in symptoms and health-related quality of life, and comparable safety profile. OBJECTIVE: To assess the impact of secukinumab versus that of ustekinumab on complete relief from psoriasis-related symptoms, time to response in terms of health-related quality of life, and cumulative benefit among patients with moderate-to-severe plaque psoriasis. METHODS: Psoriasis-related pain, itching, and scaling and the Dermatology Life Quality Index (DLQI) score were compared between treatments on the basis of time to complete relief of symptoms and time to DLQI response in the CLEAR trial. Cumulative benefit over 52 weeks based on Psoriasis Area and Severity Index score, symptom relief, and DLQI response were evaluated by area under the curve analysis. RESULTS: Significantly more patients treated with secukinumab achieved complete relief of pain at weeks 16 and 52 (all P \u3c .05). Complete relief of itching and scaling occurred significantly faster with secukinumab (median, 4 weeks faster for itching and 8 weeks faster for scaling [P \u3c .001]). Response as measured by the DLQI was 4 weeks faster with secukinumab (P \u3c .0001). Cumulative benefits were greater with secukinumab (all P \u3c .05). LIMITATIONS: Analyses were post hoc. CONCLUSION: This patient-reported outcome analysis confirms greater and sustained benefits of secukinumab versus those of ustekinumab treatment on patients\u27 lives

Patient-reported outcomes in capmatinib-treated patients with METex14-mutated advanced NSCLC: Results from the GEOMETRY mono-1 study

Introduction: Capmatinib, a MET inhibitor, showed substantial antitumour activity with manageable side effects in patients with MET exon 14 (METex14)-mutated advanced non-small cell lung cancer (aNSCLC) in the GEOMETRY mono-1 study. We report patient-reported outcomes (PROs) from this study. Methods: Enrolled treatment-naïve (1L) or pre-treated (2L+) patients with aNSCLC with a METex14-skipping mutation received 400 mg capmatinib twice daily during 21-day treatment cycles. PROs were collected at baseline and every six weeks thereafter using EORTC QLQ-C30 global health status/quality of life (GHS/QoL), QLQ-LC13 symptoms, and EQ-5D-5L visual analogue scale (VAS) questionnaires. Results: As of 6 January 2020, 27/28 1L and 65/69 2L+ patients had completed PROs at baseline; compliance rates remained >70%. Cough improved early, with meaningful improvements (≥10-point change from baseline) observed throughout cycles (mean change from baseline [SD] by week 7: 1L −13.0 [39.9], 2L+ −8.2 [28.4]; week 43: 1L −28.2 [26.7], 2L+ −10.5 [27.3]). QoL, assessed by GHS/QoL and VAS, improved by week 7 in 1L and 2L+ patients, with improvements generally sustained over time. Median time to definitive deterioration (TTDD) in GHS/QoL was 16.6 months (95% CI: 9.7, not estimable [NE]) in 1L and 12.4 months (95% CI: 4.2, 19.4) in 2L+ patients. Median TTDD for dyspnoea was 19.4 months (95% CI: 12.4, NE) and 22.1 months (95% CI: 9.9, NE) for 1L and 2L+ patients, respectively, and NE for cough and chest pain. Conclusions: Capmatinib was associated with clinically meaningful improvements in cough and preserved QoL, further supporting its use in patients with METex14-mutated aNSCLC. Trial registration: ClinicalTrials.gov registry number: NCT02414139