Analysis Of Patient-reported Outcomes Research Articles

Comprehensive review of statistical methods for analysing patient-reported outcomes (PROs) used as primary outcomes in randomised controlled trials (RCTs) published by the UK’s Health Technology Assessment (HTA) journal (1997–2020)

ObjectivesTo identify how frequently patient-reported outcomes (PROs) are used as primary and/or secondary outcomes in randomised controlled trials (RCTs) and to summarise what statistical methods are used for the analysis...

Prediction of all-cause mortality from 24\xa0month trajectories in patient-reported psychological, clinical and quality of life outcomes in uveal melanoma patients

A number of patient-reported outcomes (PROs) predict increased mortality after primary cancer treatment. Studies, though, are sometimes affected by methodological limitations. They often use control variables that poorly predict life expectancy, examine only one or two PROs thus not controlling potential confounding by unmeasured PROs, and observe PROs at only a single point in time. To predict all-cause mortality, this study used control variables affording good estimates of life expectancy, conducted multivariate analyses of multiple PROs to identify independent predictors, and monitored PROs two years after diagnosis. We recruited a consecutive sample of 824 patients with uveal melanoma between April 2008 and December 2014. PROs were variables shown to predict mortality in previous studies; anxiety, depression, visual and ocular symptoms, visual function impairment, worry about cancer recurrence, and physical, emotional, social and functional quality of life (QoL), measured 6, 12 and 24 months after diagnosis. We conducted Cox regression analyses with a census date of December 2018. Covariates were age, gender, marital and employment status, self-reported co-morbidities, tumor diameter and thickness, treatment modality and chromosome 3 mutation status, the latter a genetic mutation strongly associated with mortality. Single predictor analyses (with covariates), showed 6-month depression and poorer functional QoL predicting mortality, as did 6–12 month increases in anxiety and 6–12 month decreases in physical and functional QoL. Multivariate analyses using all PROs showed independent prediction by 6-month depression and decreasing QoL over 6–12 months and 12–24 months. Elevated depression scores six months post-diagnosis constituted an increased mortality risk. Early intervention for depressive symptoms may reduce mortality.

P112. Cervical disc replacement for radiculopathy versus myeloradiculopathy: An MCID analysis

<h3>BACKGROUND CONTEXT</h3> Several previous randomized controlled trials have documented the success of cervical disc replacement (CDR) in treating radiculopathy and/or myelopathy, but many did not systematically compare outcomes of patients with radiculopathy versus those with myelopathy. Currently, there is still controversy about whether CDR utilization in patients with components of myelopathy can result in equivalent outcomes when compared to its use in patients with only radiculopathy. <h3>PURPOSE</h3> The purpose of the present study was to compare the minimally clinically important difference (MCID) across multiple patient-reported outcomes (PROs) in patients undergoing CDR for cervical spondylotic radiculopathy versus myeloradiculopathy. <h3>STUDY DESIGN/SETTING</h3> Retrospective review of prospectively collected data. <h3>PATIENT SAMPLE</h3> Patients who underwent one or two-level CDR with radiculopathy versus myeloradiculopathy. <h3>OUTCOME MEASURES</h3> Neck Disability Index (NDI), VAS-Neck, VAS-Arm, Short Form-12 Health Survey (SF-12) Physical Component Score (PCS), SF-12 Mental Component Score (MCS), PROMIS Physical Function (PF). <h3>METHODS</h3> Demographic variables and operative characteristics were analyzed for differences between patients with radiculopathy versus myeloradiculopathy. PROs were assessed for differences between the two diagnosis groups as well as improvements within each group following surgery. An MCID analysis of PROs for each diagnosis group was performed and the percentage of patients achieving the MCID was compared between the two diagnosis groups. <h3>RESULTS</h3> A total of 85 patients were included in the present study, of which 48 (56%) had radiculopathy and 37 (44%) had myeloradiculopathy. Average follow-up was 13.4 months. There were no significant differences in preoperative demographic variables, or the number and distribution of cervical levels treated between the two diagnosis groups. There were no significant differences in preoperative NDI, Neck-VAS, Arm-VAS, SF-12 PCS, SF-12 MCS, and PROMIS PF scores between the two groups. At the final postoperative visit, there was no significant difference in each PRO assessed between the radiculopathy and myeloradiculopathy groups and both groups demonstrated statistically significant improvement in each PRO compared to preoperative values (P<0.02).MCID analysis demonstrated that at 6-week, 12-week, and final postoperative follow-up there was no significant difference in the percentage of patients with radiculopathy or myeloradiculopathy achieving the MCID for each PRO assessed. In both diagnosis groups the percentage of patients achieving the MCID for each PRO continued to increase from the 6-week to final postoperative follow-up except for the SF-12 MCS in patients with myeloradiculopathy. <h3>CONCLUSIONS</h3> This is the first study to compare the MCID across various PROs in patients with radiculopathy versus myelopathy undergoing CDR. The percentage of patients achieving the MCID was not significantly different at each postoperative period assessed in the radiculopathy and myeloradiculopathy groups. In addition, the percentage of patients achieving the MCID continued to increase from 6-weeks to final follow-up in both groups for almost all PROs assessed. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Review of patient-reported outcomes in multiple myeloma registrational trials: highlighting areas for improvement

Over the past 13 years, there have been advances in characterizing the patient experience in oncology trials, primarily using patient-reported outcomes (PROs). This review aims to provide details on the PRO measures and analyses used in multiple myeloma (MM) registrational trials. We identified registrational trials supporting MM indications from 2007 to 2020 from FDA databases. Trial protocols, statistical analysis plans, and clinical study reports were reviewed for PRO measures used, collection methods, statistical analyses, baseline and instrument completion definitions, and thresholds for clinical meaningfulness. Twenty-five trials supporting 20 MM indications were identified; 17 (68%) contained submitted PRO data. Of the 17 trials, 14 were randomized controlled trials and the remainder were single-arm trials. All but one trial were open label trials. Seven trials collected data electronically and five in paper format. The majority of trials evaluated at least two PRO measures (82%) with two trials (12%) utilizing four measures. Nine unique PRO measures were used, most commonly the EORTC QLQ-30 (87%), EQ-5D (65%), and QLQ-MY20 (47%). All 17 (100%) trials provided descriptive summaries, 10 (59%) carried out longitudinal mixed model analysis, 9 (53%) conducted responder analysis, and 2 (12%) did a basic inferential test. We noted substantial heterogeneity in terms of PRO collection methods, measures, definitions, and analyses, which may hinder the ability to effectively capture and interpret patient experience in future MM clinical trials. Further research is needed to determine the most appropriate approaches for statistical and analytical methodologies for PRO data in MM trials.

Province-Wide Analysis of Patient-Reported Outcomes for Stage IV Non-Small Cell Lung Cancer.

In Ontario, Canada, patient-reported outcome (PRO) evaluation through the Edmonton Symptom Assessment System (ESAS) has been integrated into clinical workflow since 2007. As stage IV non-small cell lung cancer (NSCLC) is associated with substantial disease and treatment-related morbidity, this province-wide study investigated moderate to severe symptom burden in this population. ESAS collected from patients with stage IV NSCLC diagnosed between 2007 and 2018 linked to the Ontario provincial health care system database were studied. ESAS acquired within 12 months following diagnosis were analyzed and the proportion reporting moderate to severe scores (ESAS ≥4) in each domain was calculated. Predictors of moderate to severe scores were identified using multivariable Poisson regression models with robust error variance. Of 22,799 patients, 13,289 (58.3%) completed ESAS (84,373 assessments) in the year following diagnosis. Patients with older age, with high comorbidity, and not receiving active cancer therapy had lower ESAS completion. The majority (94.4%) reported at least one moderate to severe symptom. The most prevalent were tiredness (84.1%), low well-being (80.7%), low appetite (71.7%), and shortness of breath (67.8%). Most symptoms peaked at diagnosis and, while declining, remained high in the following year. On multivariable analyses, comorbidity, low income, nonimmigrants, and urban residency were associated with moderate to severe symptoms. Moderate to severe scores in all ESAS domains aside from anxiety were associated with radiotherapy within 2 weeks prior, whereas drowsiness, low appetite and well-being, nausea, and tiredness were associated with systemic therapy within 2 weeks prior. This province-wide PRO analysis showed moderate to severe symptoms were prevalent and persistent among patients with metastatic NSCLC, underscoring the need to address supportive measures in this population especially around treatments. In this largest study of lung cancer patient-reported outcomes (PROs), stage IV non-small cell lung cancer patients had worse moderate-to-severe symptoms than other metastatic malignancies such as breast or gastrointestinal cancers when assessed with similar methodology. Prevalence of moderate-to-severe symptoms peaked early and remained high during the first year of follow-up. Symptom burden was associated with recent radiation and systemic treatments. Early and sustained PRO collection is important to detect actionable symptom progression, especially around treatments. Vulnerable patients (e.g., older, high comorbidity) who face barriers in attending in-person clinic visits had lower PRO completion. Virtual PRO collection may improve completion.

Health-related quality of life (HRQoL) in patients with relapsed/refractory multiple myeloma (RRMM) treated with pomalidamide and dexamethasone ± subcutaneous daratumumab: Patient-reported outcomes (PROs) in APOLLO.

8046 Background: APOLLO (NCT03180736) is a phase 3 trial of pomalidomide and dexamethasone (Pd) ± subcutaneous daratumumab (1800 mg, co-formulated with recombinant human hyaluronidase PH20 in 15 mL) in patients with RRMM and ≥1 prior line of therapy including lenalidomide and a proteasome inhibitor. After 16.9 months (mo) median follow-up, D-Pd significantly reduced the rate of progression or death by 37% relative to Pd. Patients with RRMM have reduced HRQoL compared with age- and sex-matched populations. Here, we present PROs from the APOLLO trial. Methods: Patients were randomized 1:1 to D-Pd or Pd and treated in 28-day cycles until disease progression/unacceptable toxicity. PROs were assessed on Day 1 of each cycle using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30), EORTC QLQ Multiple Myeloma Module 20-item (MY20), and EuroQol 5-dimensional descriptive system. PRO analyses were performed on patients from the intent-to-treat population with a baseline (BL) and ≥1 post-BL assessment. Treatment effect was assessed by a mixed effects model with repeated measures. Time to worsening was estimated using the Kaplan-Meier method. Results: A total of 304 patients were included (151 D-Pd, 153 Pd). Median treatment duration was 11.5 mo with D-Pd vs 6.6 mo with Pd. At Cycle 16 (Cyc 16), 63 and 40 patients remained on treatment in the D-Pd and Pd groups, respectively. Compliance rates for PRO instruments were high and comparable between groups. Patients treated with D-Pd had a reduction in pain (maximum improvement: 6.8 points at Cyc 12) measured with the EORTC QLQ-C30 and no mean change in disease symptoms or the treatment side effects subscales of the EORTC QLQ-MY20. Group mean physical and emotional functioning were unchanged from BL with D-Pd but worsened in the Pd group (maximum worsening: 6.4 at Cyc 4 and 9.1 points at Cyc 14). The proportion of patients with a meaningful improvement from BL was 55.0% vs 49.0% for disease symptoms, 43.0% vs 35.3% for physical functioning, and 41.7% vs 31.4% for emotional functioning with D-Pd vs Pd, respectively. Median time to worsening was ̃4 mo, except for the disease symptoms subscale (̃10 mo); there were no differences between groups. Conclusions: When daratumumab was added to Pd, patients did not experience any decrements in HRQoL while on treatment, but some patients experienced reductions in pain as well as clinically meaningful improvements in symptoms and emotional/physical function. These findings complement the clinical benefits of D-Pd in RRMM patients and further support its use in this RRMM population. Clinical trial information: NCT03180736.

The PanOptix Trifocal IOL vs the ReSTOR 2.5 Active Focus and ReSTOR 3.0-Add Multifocal Lenses: A Study of Patient Satisfaction, Visual Disturbances, and Uncorrected Visual Performance.

PurposeTo compare spectacle independence, patient-reported outcomes (PROs), and dysphotopsia after multifocal intraocular lens (IOL) implantation with the AcrySof PanOptix trifocal or the ReSTOR +2.5/3.0 D or ReSTOR +2.5 D mini-monovision multifocal IOL.Patients and MethodsProspective, open-label, multicenter analysis of PROs, spectacle independence, and satisfaction among patients undergoing cataract surgery who had been implanted at least 1 month previously with AcrySof IQ PanOptix or PanOptix Toric trifocal (n = 59) IOLs bilaterally. Results were compared to outcomes from a similar study with the AcrySof ReSTOR 2.5/3.0 or the ReSTOR ActiveFocus 2.5 mini-monovision lens [n = 191]).ResultsSpectacle independence was significantly higher in the PanOptix cohort, with 83% of patients “never” needing glasses for any activity versus 36% in the ReSTOR 2.5 mini-monovision and 34% in the ReSTOR 2.5/3.0 cohorts. No significant differences in patient satisfaction rates were reported between the three cohorts. Glare and halo were rated “extremely” noticeable more with the PanOptix (10%) than with the ReSTOR 2.5 mini-monovision (1%) or ReSTOR 2.5/3.0 (3%). BCVA differences were not statistically significant, and no new safety concerns were reported.ConclusionThe AcrySof PanOptix trifocal provides significantly greater spectacle independence across all measured activities than the AcrySof ReSTOR multifocal IOLs.

Characterization of version in the dysplastic hip and the need for subsequent femoral derotational osteotomy after periacetabular osteotomy.

Hip dysplasia is a three-dimensional pathomechanical condition that is often more complex than the standard method of measuring lateral center edge angle (CEA) can quantify. Yet there is a paucity of literature examining the differences in version seen between dysplastic and non-dysplastic femoroacetabular impingement (FAI) hips, the relationship of acetabular and femoral version (FV) within dysplastic hips and the contribution of each of these factors to symptoms and outcomes of dysplasia treatment. We sought to describe the acetabular version (AcetV) and FV in dysplastic hips and quantify how these measurements compared with non-dysplastic FAI hips. We also sought to analyze the association of these factors with patient-reported outcomes (PROs) after periacetabular osteotomy (PAO) and determine the need for subsequent femoral derotational osteotomy after PAO. A total of 113 dysplastic patients who underwent PAO (92% female, mean age 24) were compared with 1332 (45% female, mean age 25) non-dysplastic FAI (CEA > 25°) patients. We found that dysplastic hips had a statistically higher AcetV and FV than non-dysplastic FAI hips. There was a very weak correlation between AcetV and FV in dysplastic hips, suggesting that patients with higher AcetV did not necessarily have higher FV. There was no association with AcetV or FV and patient outcomes in our very limited analysis of PROs after PAO, and only 5% of patients with excessive FV (>20°) required subsequent femoral derotational osteotomy, suggesting that in a majority of patients with hip dysplasia, FV may not impact the post-operative clinical course.

Abstract 12613: Patient-reported Outcomes in a Multidisciplinary Electrophysiology-psychology Ventricular Arrhythmia Clinic

Background: Ventricular arrhythmias (VAs) and their treatment have been associated with psychological distress and poorer quality of life (QOL) in research studies. Patient-reported outcome (PRO) measures are beginning to be introduced in clinical settings and early experiences with their clinical utility warrant attention. We wanted to describe PROs of patients attending a multidisciplinary VA clinic in order to elucidate roles that PRO measures might have in clinical settings. Methods: In this retrospective study, we enrolled patients with history of sustained VA and/or ICD shock at their initial visit to a clinic staffed by an electrophysiologist and a psychologist. Patients completed several PRO measures including the following: anxiety and depression symptoms, visual analog scales for health status and QOL, cardiac device acceptance, ICD shock anxiety, and general cardiac anxiety. Here we report total scores for general PROs and item-level analysis of the three cardiac-specific measures. Results: A total of 57 patients (56 ±15 years; 84% male) were included; 39% had a history of sudden cardiac arrest, 70% had prior ICD shock and 44% had previously undergone VA ablation. Symptoms that exceeded clinical thresholds were common for anxiety (49%) and depression (20%). On 0-100 visual analogue scales, the mean rating for health status was 57 ± 16 and for QOL was 66 ± 18. Item-level analysis of cardiac-specific PROs revealed that between 40% and 50% of patients endorsed specific concerns regarding return to work, resumption of physical activities, and sexual relations (Table 1). Conclusion: Among patients attending a VA clinic, elevated symptoms of anxiety and depression were common and self-reported health status and QOL were low. Although PRO total scores provided general information, review at the individual item level provided critical information about potential sources of anxiety that can guide cardiologists during discussions with patients.

Quality of patient-reported outcome reporting according to the CONSORT statement in randomized controlled trials with glioblastoma patients.

Randomized controlled trials (RCTs) represent the best evidence in oncology research. Glioblastoma is the most frequent and deadly primary brain tumor, affecting health-related quality of life. An important end point is patient-reported outcomes (PROs). There are no data regarding how well publications of glioblastoma RCTs report PROs. A specific PRO extension of the Consolidated Standards of Reporting Trials (CONSORT) statement was created to improve the quality of reporting. The aim of this study was to evaluate adherence to the CONSORT-PRO statement in reporting RCTs addressing the treatment of patients with glioblastoma. PRO analysis methodology was explored and criteria associated with higher quality of reporting were investigated. From PubMed/MEDLINE and the Cochrane Library databases, all phase 2 and 3 RCTs related to glioblastoma published between 1995 and 2018 were reviewed according to the CONSORT-PRO statements. An overall quality score on a 0 to 100 scale was defined based on these criteria and factors associated with this score were identified. Forty-four RCTs were identified as relevant according to predefined criteria. The median overall quality score was 26. No difference was observed regarding reporting quality over the years. CONSORT-PRO items concerning data collection and analysis were poorly reported. Thirty-four trials (77%) used longitudinal data. The most frequent statistical method for PROs analysis was the mean change from baseline (63%). Factors associated with improved overall quality score were the presence of a secondary publication dedicated to PROs results, the statement of any targeted dimensions, and when trials reported results using multiple methods. Despite the importance of measuring PROs in patients with glioblastoma, employment of the CONSORT-PRO statement is poor in RCTs.

QOLP-02. PATIENT-REPORTED OUTCOMES FOLLOWING PERTUZUMAB PLUS HIGH-DOSE TRASTUZUMAB IN PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER (MBC) AND CENTRAL NERVOUS SYSTEM (CNS) PROGRESSION POST-RADIOTHERAPY

Abstract Effective therapies are needed for the treatment of patients with HER2-positive MBC who develop brain metastases. In the open-label, phase II PATRICIA study (NCT02536339), 40 patients with HER2-positive MBC with CNS metastases and CNS progression post-radiotherapy (median age 48 years [range, 34–69]; prior CNS treatment [whole brain radiotherapy 71%, stereotactic radiosurgery 59%, both 31%]) were enrolled to receive pertuzumab plus high-dose trastuzumab (6-mg/kg weekly) until CNS or systemic disease progression or unacceptable toxicity. Following a median (range) treatment duration of 4.5 (0.3–37.3) months, the CNS-confirmed objective response rate per Response Assessment in Neuro-Oncology Brain Metastases criteria (primary endpoint) was 11% (95% confidence interval: 3.03, 25.42), and the clinical benefit rate at 4 months was 68%, indicating sustained clinical stability. Patient-reported outcomes (PROs) were evaluated using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT), which includes sub-scales for symptom severity (average of 13 core symptom and 9 brain-tumor specific items) and symptom interference (average of 6 interference-with-life items representing overall symptom distress). Among 36 patients included in the PRO analyses, mean (standard deviation [SD]) symptom severity scores at baseline and weeks 12 and 28 were 1.65 (1.62), 2.24 (2.14), and 1.94 (2.55), respectively. Mean (SD) symptom interference scores at baseline and weeks 12 and 28 were 2.51 (2.63), 2.81 (3.39), and 1.76 (2.43), respectively. Mean (SD) changes in symptom severity and interferences scores from baseline to week 12 were 0.34 (1.54) and 0.33 (3.08), respectively. On average, patients who did not achieve stable disease or better in the CNS following treatment had worsened symptom severity and symptom interference scores over 12 weeks, while those with stable disease or better in the CNS exhibited stable or improving scores. Pertuzumab plus high-dose trastuzumab provided clinical benefit to the majority (68%) of patients in PATRICIA, without a decrement in quality of life.

Effect of Pembrolizumab Monotherapy Versus Brentuximab Vedotin (BV) on Symptoms Associated with Health-Related Quality of Life (HRQoL) in Relapsed/Refractory (R/R) Classical Hodgkin Lymphoma (cHL) in the Randomized, Phase 3, Keynote-204 Study

Effect of Pembrolizumab Monotherapy Versus Brentuximab Vedotin (BV) on Symptoms Associated with Health-Related Quality of Life (HRQoL) in Relapsed/Refractory (R/R) Classical Hodgkin Lymphoma (cHL) in the Randomized, Phase 3, Keynote-204 Study

Safety, Efficacy, and Patient-Reported Outcomes of Venetoclax in Combination with Azacitidine for the Treatment of Patients with Higher-Risk Myelodysplastic Syndrome: A Phase 1b Study

Safety, Efficacy, and Patient-Reported Outcomes of Venetoclax in Combination with Azacitidine for the Treatment of Patients with Higher-Risk Myelodysplastic Syndrome: A Phase 1b Study

Characterization of Patient-Reported Outcomes in Multiple Myeloma Registrational Trials Submitted to the U.S. FDA

Introduction Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells. The US Food and Drug Administration (FDA) has approved numerous therapies for the treatment of MM over the past 13 years. During the same time period, there have been advances in characterizing the patient experience in oncology clinical trials, primarily using patient-reported outcomes (PRO). Although there have been advances in MM and collection of patient experience in clinical trials, this review aims to provide details on the heterogeneity of PRO measures and data analyses used in MM registrational trials. Methods We reviewed FDA databases for NDA/BLA submissions supporting therapies to treat patients with MM between 2007 and 2020. Pivotal trial protocols, clinical study reports, and FDA clinical/ statistical reviews supporting each application were reviewed for descriptions of included PROs. We focused on PRO measures, collection methods, baseline definition, assessment frequency, compliance, definition of thresholds for clinically meaningfulness, and statistical methods for analysis of PRO. Results We examined the results from 25 clinical trials that led to 20 new indications. PRO data were included in 17 of the 25 trials (68%). Of the 17 trials with PRO data, three were single arm trials, and the remainder were randomized trials. All trials were open label except for one blinded randomized trial. Seven trials collected data electronically, five in paper format, and five trials did not specify the collection format. The majority of trials had at least two PRO measures (82%) with two trials (12%) utilizing four measures. Among trials included for analysis, nine unique PRO measures were used, most commonly the EORTC QLQ-30 (87%), EQ-5D (65%), both cancer agnostic and QLQ-MY20 (47%), specifically for MM patients. We found differences in terms of definition of baseline. One trial defined measurements taken only at screening as the baseline assessment, while the remainder defined baseline as any measurement taken on or before day 1 cycle 1. Assessment frequency was highly variable (e.g. every cycle, every other cycle, every three months) and was largely dependent on cycle length (ranged from 21 to 42 days). We also noted that assessment may have been after a period of drug washout (e.g. the anti-MM regimen was administered on days 1-21 of a 28 day cycle; PRO assessment occurred on day 1 of the next cycle, thus following a 7-day washout). Definition of compliance of the PRO measures varied across the trials ranging from "completing all items" (6%), "completing 50% of the items" (12%), and "completing enough items to calculate the score in any domain" or some variant (82%). There was variability in the definition and justification of clinically meaningful thresholds across trials despite use of the same instrument and similar MM populations. Differences in statistical methods used for analyses of the PRO endpoints were also noted when analyzing data from the same measure across trials. For example, one of the two trials using the BPI-SF analyzed pain severity and intensity as composite endpoints (change from baseline analysis using a mixed model with treatment arm, time point, and baseline score as covariates). The other trial using the BPI-SF used pain response which was defined as a 30% reduction from baseline in worst pain score over the last 24 hours without an increase in analgesic use at 2 consecutive evaluations as an endpoint, and used the stratified Cochran-Mantel-Haenszel test to report treatment differences. Conclusions We encountered substantial heterogeneity in terms of PRO collection methods, measures, definitions and analyses in recent MM registrational trials. These differences may hinder the utility of this data for healthcare policy as well as clinician and patient decision making. FDA has proposed a core outcome set to be included in cancer clinical trials which includes assessment of patient-reported adverse events, disease symptoms, physical function, role function, and overall side effect bother. Use of this core outcome set in future MM registration trials is one step towards consistency in PRO collection and analysis. Further work needs to be done to determine the best approach for statistical and analytical methodologies. Table Disclosures No relevant conflicts of interest to declare.

PATIENT-REPORTED OUTCOME AFTER ILEAL NEOBLADDER

(Objectives) Investigation of patient-reported outcome (PRO) after ileal neobladder for bladder cancer. (Patients and methods) Forty patients who underwent radical cystectomy and ileal neobladder between July 2007 and December 2017 were asked to complete a questionnaire. PRO was evaluated using the Medical Outcomes Study Short Form-8 (SF-8) for general health-related quality of life (QOL) and the Bladder Cancer Index and the Japanese version of the Functional Assessment of Cancer Therapy-Bladder for disease specific QOL. Patients were divided into two groups according to the postoperative period (early and late), and the differences in questionnaire results between the groups were evaluated. (Results) All scores on the SF-8 were over 50 points, exceeding the Japanese national standard of 50 points for all items. The physical and mental summary scores were also favorable. For disease-specific QOL, only daytime incontinence was significantly higher in the late group, with daytime incontinence two or more times per week at 42.1%, compared to 20.0% in the early group (P=0.0403). A comparison of daytime urinary incontinence in four groups during the postoperative period showed that urinary incontinence was least frequent among patients between 64 and 101 months after surgery; patients in this group were also the youngest in age at the time of surgery. (Conclusions) Cross-sectional analysis of PRO revealed that patients with ileal neobladder had good general health-related QOL after surgery, but urinary incontinence was a significant problem.

Abstract CT071: Talazoparib (TALA) in germline BRCA1/2 (gBRCA1/2)-mutated human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC): Final overall survival (OS) results from randomized Phase 3 EMBRACA trial

Abstract Background: TALA significantly prolonged progression-free survival vs physician's choice of chemotherapy (PCT) (hazard ratio [HR] 0.54 [95% CI 0.41-0.71]; P &amp;lt; 0.001) and improved patient-reported outcomes (PRO) in patients (pts) with HER2- ABC (locally advanced/metastatic) with a gBRCA1/2 mutation. We report results of the final OS analysis (secondary endpoint). Methods: Pts randomized 2:1 to TALA or PCT. OS HR was based on stratified Cox regression model (treatment as covariate); P value on stratified log-rank test. Results: 431 pts were randomized (287 TALA/144 PCT), 412 treated (286 TALA/126 PCT). By Sept 30, 2019, 216 deaths (75.3%) occurred for TALA and 108 deaths (75.0%) PCT; median follow-up 44.9 and 36.8 months, respectively. HR for OS was 0.85 (95% CI 0.67-1.07; P = 0.17); survival probability was higher for pts receiving TALA at 24, 36, and 48 months (Table 1). OS results were consistent across subgroups, eg by prior platinum or hormone receptor status. Most pts received post-study therapies; 32.6% of pts in the PCT arm received a PARP inhibitor post-study (4.5% for TALA arm). Grade 3-4 AEs occurred in 69.6% (TALA) and 64.3% (PCT) pts; AEs leading to permanent treatment discontinuation (excluding progressive disease) occurred in 5.9% and 8.7% of pts. Extended follow-up showed statistically significant overall improvements and delays in time to definitive clinically meaningful deterioration in both global health status/QoL and breast symptoms scales favoring TALA vs PCT (P &amp;lt; 0.01 for all), consistent with initial PRO analyses. Table 1.OS and post-study therapy (intent-to-treat)Talazopariboral 1 mg QDN = 287PCTaN = 144Deaths (%)216 (75.3)108 (75.0)HR (95% CI)0.85 (0.67-1.07); P = 0.17Median, mo. (95% CI)b19.3 (16.6-22.5)19.5 (17.4-22.4)Survival probability (95% CI) at Monthc120.71 (0.66-0.76)0.74 (0.66-0.81)240.42 (0.36-0.47)0.38 (0.30-0.47)360.27 (0.22-0.33)0.21 (0.14-0.29)480.19 (0.14-0.25)0.07 (0.02-0.15)Post-study antineoplastic therapy, n (%)233 (81.2)110 (76.4)PARP inhibitor, n (%)13 (4.5)47 (32.6)Platinum-based therapy, n (%)133 (46.3)60 (41.7)CI, confidence interval; HR, hazard ratio; KM, Kaplan-Meier; mo., months; OS, overall survival; PARP, poly(ADP-ribose) polymerase; QD, once daily.aPCT, physician's choice of chemotherapy (capecitabine, eribulin, gemcitabine, vinorelbine).bDuration of OS based on KM estimates.cProbability estimated from the KM curve and CI calculated with product-limit method. Conclusions: In gBRCA1/2-mutated HER2- ABC, TALA did not significantly improve OS over PCT (HR 0.85; 95% CI 0.67-1.07; P = 0.17); analysis not adjusted for subsequent therapies. TALA was generally well-tolerated with no new safety signals. PRO continued to favor TALA. Funding: Pfizer (Medivation) Citation Format: Jennifer K. Litton, Sara A. Hurvitz, Lida A. Mina, Hope S. Rugo, Kyung-Hun Lee, Anthony Gonçalves, Sami Diab, Natasha Woodward, Annabel Goodwin, Rinat Yerushalmi, Henri Roché, Young-Hyuck Im, Wolfgang Eiermann, Ruben G. Quek, Tiziana Usari, Silvana Lanzalone, Akos Czibere, Joanne L. Blum, Miguel Martin, Johannes Ettl. Talazoparib (TALA) in germline BRCA1/2 (gBRCA1/2)-mutated human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC): Final overall survival (OS) results from randomized Phase 3 EMBRACA trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT071.

Trends in PRO reporting in clinical trials leading to GU cancer drug approvals from 2007 to 2018.

641 Background: Having standardized and high quality reporting of patient reported outcomes (PRO), especially in clinical trials that establish standards of care in oncology is important for patient centered care. This study assessed the status of reporting and quality of analysis of PROs in FDA approved drugs for genitourinary malignancies. Methods: We conducted a systematic review of the FDA archives to identify urological cancer drugs approved between 2007-2018. We retrieved the clinical trials that led to these drug approvals from ClinicalTrials.gov and PubMed. We systematically screened for PROs and reviewed their analytic tools and interpretation methods reported in their published manuscripts and study protocols. A clinical trial was considered to include PROs if they were reported in either the primary or a subsequent manuscript. Results: We identified 22 clinical trials leading to FDA approval of urological cancer drugs between 2007-2018. Only 63% of trials had published PROs. PROs were reported in the primary clinical trial manuscripts for two drugs (9%), and in a secondary PRO manuscript for 12 drugs (54%). The median time between the primary and secondary papers was 12 months (IQR:7.5-26 months). Among the 14 published PRO papers, the hypothesis was broad in 79%, and not reported in 21%. PROs were never included as a primary endpoint of a study. Instead, PROs were reported as secondary endpoints in 5 (36%) and as exploratory endpoints in 7 (50%) studies, while two papers (14%) did not mention PRO reporting in their endpoints. The most common PRO instruments were EQ-5D (64%) and FACT-P (50%). In 92% of PRO papers, statistical analyses were conducted to account for missing data. Control for type I error was needed but not done in 57% of the trials. Conclusions: Delays in publication of PROs occur regularly in trials leading to drug approval in GU malignancies. Our study highlights the need to enhance standardization of the analysis and interpretation of PROs to maximize the value of this data for drug development and approval.

Abstract P5-12-09: Patient-reported outcomes (PROs) during one year of adjuvant enzalutamide for the treatment of early stage androgen receptor positive (AR+) triple negative breast cancer

Abstract BACKGROUND: A subset of TNBC expresses a luminal signature and demonstrates AR-dependence. Enzalutamide (ENZA), an AR-antagonist, has activity with metastatic AR+ TNBC, with a clinical benefit rate of 33% (Traina et al, JCO 2018). We recently demonstrated that one year (y) of adjuvant ENZA is feasible in early stage, AR+ TNBC, with no new safety signals observed (Traina ASCO 2019). Fatigue was the most common, treatment (tx)-related, adverse event of any grade according to investigator assessment (24%). Here we report per-protocol planned secondary analyses of PROs during one year of ENZA including quality of life (QoL), fatigue, and self-reported physical activity (NCT02750358). METHODS: Eligible patients have Stage I-III, ER/PR &amp;lt;1%, HER2(-), AR ≥1% breast cancer and completed all planned standard of care surgery, chemotherapy and radiation within 6 months of study start. Tx = ENZA 160mg orally daily for 1y with the option to extend tx to 2y as per patient preference. Clinician-reported toxicities (NCI CTCAEv4) were assessed every 4 weeks for 12 weeks, then every 3 months. Total study N=50 patients. PROs were assessed every 12 weeks. We examined serial changes in overall QoL (functional assessment of cancer therapy – breast (FACT-B), fatigue (FACIT-fatigue) and exercise behavior (total exercise minutes/week over past 7 days) from pre-treatment and every 3 months thereafter until month 12. All analyses are exploratory and consist of descriptive summaries. RESULTS: Between 5/2016 and 6/2018, 50 patients were enrolled. As of 6/27/19, 34 patients completed 1y of ENZA; 15 patients are off tx: recurrence (3), toxicity (5), nonadherence (4), and consent withdrawal (3). Patients evaluable for PRO (N): baseline (50), 12 weeks (43) and 52 weeks (34). Median scores on FACT-B and fatigue scales remained stable over the course of adjuvant ENZA in the 1st year of therapy (Table). Self-reported exercise increased during this period. Table. Median scores (range) for PROs during 1 year of adjuvant ENZATime PointBaselineWeek 12Week 52FACT-G88.0 (53.5-105.0)82.0 (36.4-105.0)89.5 (58.0-105.0)Breast Cancer Subscale28.5 (15.6-39.0)29.0 (9.0-40.0)29.0 (19.0-40.0)Total118.0 (77.0-141.0)111.0 (45.4-145.0)121.0 (83.0-145.0)FACT-B trial outcome index73.0 (43.0-92.0)73.0 (25.7-96.0)76.9 (51.0-96.0)FACIT43.0 (17.0-52.0)39.0 (10.0-52.0)43.0 (11.0-52.0)Total Exercise (min/week)120 (0-1260)152 (0-3120)180 (0-2580) CONCLUSIONS: Patient reported outcomes of health related QOL remain stable when ENZA is administered for 1 year in the adjuvant setting. Self-reported time spent engaged in physical exercise increased numerically during 1y of therapy. During presentation, additional analyses will be reported including QOL at additional time points, relationship of FACT-B score with FACIT fatigue score and exercise, and QOL changes in relation to relative dose intensity of ENZA, toxicity and off study reason. Citation Format: Tiffany A Traina, Lee W Jones, Victoria Blinder, Jessica Scott, Leigh Ann Boyle, Artavazd Arumov, Tina Alano, Sujata Patil, Patricia DeFusco, Nicholas Lamparella, Mark Robson, Ayca Gucalp. Patient-reported outcomes (PROs) during one year of adjuvant enzalutamide for the treatment of early stage androgen receptor positive (AR+) triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-12-09.

Abstract P1-19-06: Patient-reported outcomes, including work productivity, from the MONALEESA-7 trial of ribociclib plus endocrine therapy in patients with HR+/HER2− advanced breast cancer

Abstract Background: MONALEESA-7 is a Phase III study (NCT02278120) and the only dedicated trial of endocrine therapy (ET) ± a cyclin-dependent kinase 4/6 inhibitor in premenopausal patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer (ABC). The study demonstrated that the addition of ribociclib (RIB) to a nonsteroidal aromatase inhibitor (NSAI) or tamoxifen (TAM) + goserelin (GOS) significantly extended both progression-free survival (PFS; hazard ratio, 0.55; Tripathy D et al. Lancet Oncol. 2018) and overall survival (OS; hazard ratio, 0.71; Im S-A et al. N Engl J Med. 2019). Health-related quality of life (HRQOL) and work productivity are other important aspects of clinical benefit, especially in the premenopausal population. We present analyses of QOL and work productivity from MONALEESA-7. Methods: Premenopausal or perimenopausal patients with HR+/HER2− ABC were treated with RIB or placebo (PBO) + GOS with either an NSAI (letrozole or anastrozole) or TAM. A secondary endpoint was evaluation of patient-reported outcomes (PROs) for HRQOL using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire core 30 (QLQ-C30). Assessments included global health status as well as social, emotional, and physical functioning. Description of Work Productivity and Activity Impairment (WPAI) was an exploratory endpoint and was measured using the WPAI Questionnaire: General Health (WPAI:GH; V2.0). Results: Time to deterioration (TTD) ≥ 10% in EORTC QLQ-C30 global health status was prolonged with RIB vs PBO (median, 35.8 vs 23.3 months; hazard ratio, 0.665 [95% CI, 0.517-0.855]). TTD ≥ 10% in emotional functioning was also prolonged with RIB vs PBO (hazard ratio, 0.636 [95% CI, 0.488-0.828]), as was TTD ≥ 10% in social functioning (hazard ratio, 0.813 [95% CI, 0.610-1.084]) and TTD ≥ 10% in physical functioning (hazard ratio, 0.715 [95% CI, 0.526-0.972]). Compliance rates with the WPAI:GH were &amp;gt; 99% at baseline and &amp;gt; 98% at the end of treatment. Neither arm had an increase from baseline to the end of treatment in mean percentage of work missed due to overall health. Change in percent activity impairment due to overall health was comparable between treatment arms, as were change in percent impairment while working due to overall health and percent overall work impairment due to overall health. The trends observed with RIB vs PBO in the EORTC QLQ-C30 and WPAI:GH in the overall population were generally similar in the NSAI cohort. Conclusions: WPAI and global health are important considerations in the premenopausal patient population. Analysis of PROs demonstrated that TTD ≥ 10% in global health status and emotional functioning were prolonged with RIB vs PBO. Social and physical functioning were maintained in both treatment arms. Results in various WPAI domains demonstrated that productivity was also maintained in both groups. These QOL and WPAI results, in addition to the significantly longer PFS and OS results with RIB vs PBO, indicate a substantial clinical benefit with RIB treatment in premenopausal patients with HR+/HER2− ABC. Citation Format: Nadia Harbeck, Sara Hurvitz, Aditya Bardia, Fabio Franke, K. Gonvind Babu, Paul Wheatley-Price, Young-Hyuck Im, Kadri Altundag, Antonia Ridolfi, David Chandiwana, Brad Lanoue, Lakshmi Menon, Debu Tripathy. Patient-reported outcomes, including work productivity, from the MONALEESA-7 trial of ribociclib plus endocrine therapy in patients with HR+/HER2− advanced breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-06.

The role of circulating tumor DNA (ctDNA), tumor markers (TMs), and patient-reported outcomes (PROs) in predicting treatment response in patients with metastatic gastrointestinal (GI) cancer.

833 Background: Changes in ctDNA and serum TMs (CEA and CA19-9) can serve as predictors of response to systemic therapy in GI cancer patients (pts). Similarly, PROs correlate with survival and treatment response. We present a preliminary analysis of ctDNA, TMs, and PROs in predicting treatment response. Methods: We are enrolling 200 pts in a prospective study with metastatic pancreatic (PDAC), colorectal (CRC), gastroesophageal (GE), and biliary cancers. We are collecting ctDNA, TMs (CEA for all tumor types; CA19-9 for PDAC, GE, biliary), and PROs (FACT-G for QOL [higher scores indicate better QOL]; ESAS-r and PRO-CTCAE for symptoms; and PHQ-4 [consists of GAD-2 and PHQ-2 for anxiety and depression]; higher ESAS-r, PRO-CTCAE, and PHQ-4 scores reflect greater symptom burden) at baseline and 4 weeks. ctDNA is benchmarked against somatic tissue alterations, and serially assessed by digital droplet PCR. We correlated median percent change from baseline to 4 weeks for ctDNA, TMs, and PROs with treatment response (clinical benefit [CB], progressive disease [PD]). Results: From April to August 2019, we have enrolled 38/45 (84.4%) eligible pts (median age = 64 years; 36.8% female). Among these 38 pts, tumor types are PDAC (36.8%), CRC (31.6%), GE (28.9%), and biliary (2.6%). 18/38 pts were evaluable for ctDNA. Change in ctDNA was -94.5% in pts with CB (n = 10) and -19.5% in pts with PD (n = 8; p = 0.025). No correlation was observed between CEA and treatment response (p = 0.367). Change in CA19-9 was -1.5% for pts with CB and +47% for pts with PD (p = 0.019). Changes in PRO-CTCAE (p = 0.345), GAD-2 (p = 0.697), and ESAS scores (p = 0.743) did not differ between pts with CB and PD. However, changes in PHQ-2 (CB 0% v. PD +22.5%; p &lt; 0.001), PHQ-4 (CB -8.5% v. PD +5%; p = 0.015), and FACT-G (CB +30% v. PD +5%; p = 0.049) were significant. Conclusions: Preliminary analysis suggests that ctDNA and PROs demonstrate promising utility for early prediction of treatment response, with favorable performance relative to standard TMs. Further analyses of larger pt numbers in this ongoing study may clarify the use and integration of these measures to better predict pt outcomes.