Dueck, A. C.

Abstract Frailty influences treatment outcomes in older patients with multiple myeloma (MM), yet existing frailty tools capture limited geriatric domains and are incompletely studied in the context of contemporary therapies. We prospectively evaluated patient-reported comprehensive geriatric assessment (CGA) domains and their associations with treatment toxicity and patient-reported outcomes (PRO) in older adults with MM. Patients aged ≥60 years with newly diagnosed or relapsed/refractory MM initiating a new therapy completed electronic CGA and PRO questionnaires at baseline and 4 months. Outcomes included clinician- and patient-reported treatment toxicity, treatment adaptations, health care use, and health-related quality of life (HRQOL). A cumulative deficit frailty index (FI) was derived from CGA and HRQOL domains. Among 90 patients (mean age, 72 years), geriatric impairments were common, particularly physical function domains. High-grade nonhematologic toxicities were significantly associated with older age, comorbidities, patient-reported functional limitations, and anxiety. Toxicity rates on the PRO version of the Common Terminology Criteria for Adverse Events (CTCAE) were higher than on CTCAE, highlighting a discordance between physician- and patient-reported treatment toxicity. Frailty was present in 22% and associated with worse baseline HRQOL and increased high-grade nonhematologic toxicity but not treatment adaptations or health care use. Average CGA and HRQOL scores remained stable over 4 months, although individual trajectories varied. Patient-reported geriatric impairments are prevalent in older adults with MM and strongly associated with nonhematologic toxicities even in the contemporary treatment era. Physician-reported CTCAE may not fully reflect patients' symptom burden. Heterogeneity in individual geriatric trajectories during treatment emphasize the need for longitudinal assessment. This study was registered at www.clinicaltrials.gov as NCT05918185.

Background/Objectives: The PRO-CTCAE Average Composite Score (ACS), calculated as the mean of PRO-CTCAE composite scores, summarizes overall symptom and side effect burden. This study evaluated the test–retest reliability, responsiveness to change, known-groups validity, and sensitivity to group differences in the ACS. Methods: Analyses used the original PRO-CTCAE validation dataset, including lung (n = 174), breast (n = 222), and head and neck (n = 139) cancer cohorts, and data from the COMET-2 randomized phase III trial comparing cabozantinib (n = 53) and mitoxantrone–prednisone (n = 54) in men with previously treated prostate cancer. Test–retest reliability was assessed using intraclass correlation coefficients (ICCs) from two-way mixed-effects models for agreement. Responsiveness was evaluated by relating ACS change scores (Visit 1 minus follow-up Visit 2) to patient-reported global ratings of change (GRC; worsened, unchanged, or improved) using standardized response means (SRMs) and Jonckheere–Terpstra trend tests. Known-groups validity was examined by comparing mean ACS values between ECOG performance status groups (0–1 vs. 2–4). Sensitivity to treatment group differences was assessed using model-based area-under-the-curve (AUC) comparisons of longitudinal ACS trajectories. Results: Test–retest reliability was acceptable, with ICCs among GRC-defined stable patients of 0.80 (95% CI: 0.70–0.87) in lung cancer, 0.84 (95% CI: 0.77–0.89) in breast cancer, and 0.77 (95% CI: 0.63–0.86) in head and neck cancer; ICCs based on assessments completed one day apart ranged from 0.88 to 0.90. The ACS demonstrated responsiveness, with SRMs of 0.30/0.15/−0.37 (lung), 0.29/0.14/−0.40 (breast), and −0.01/−0.20/−0.56 (head/neck) for improved/no-change/worsened groups, respectively, and significant monotonic trends across GRC categories (all p < 0.01). Known-groups validity was supported by conceptually expected differences in ACS values across distinct levels of self-reported patient-reported physical functioning and ECOG performance status categories. Mean ACS values were lower among patients with good versus limited physical functioning (0.71 vs. 1.23 in lung cancer, 0.52 vs. 1.19 in breast cancer, and 0.69 vs. 1.29 in head and neck cancer) and among patients with ECOG PS 0–1 versus 2–4 (0.93 vs. 1.31, 0.74 vs. 1.22, and 0.90 vs. 1.06, respectively). In COMET-2, higher symptom burden was detected in the cabozantinib arm compared with the mitoxantrone–prednisone arm (AUC difference = 1.5, 95% CI: 0.2–2.8, p = 0.02). Conclusions: The ACS demonstrated acceptable test–retest reliability, responsiveness, and known-groups validity across multiple cancer populations. These findings support its use as a complementary summary measure of overall symptomatic adverse event burden alongside individual symptom-level analyses.

TPS2103 Background: Treatment for newly diagnosed IDH-mutant astrocytoma, WHO grade 3, is based on the results of the CATNON study, demonstrating benefit of radiotherapy followed by 12 months of adjuvant temozolomide. While temozolomide and radiotherapy significantly improved survival, the prognosis for these patients remains limited and more effective therapies are required. This trial will evaluate the benefit of the addition of the IDH1 and IDH-2 inhibitor vorasidenib to adjuvant temozolomide versus placebo following standard radiotherapy to evaluate possible improvement in outcomes. Methods: Alliance A072301 (NCT07215910) is a multicenter, double-blinded phase 3 randomized study to determine if the addition of vorasidenib to adjuvant temozolomide significantly improves progression-free survival (PFS), based on blinded central review in patients with newly diagnosed, IDH-mutant astrocytoma, WHO grade 3. Key inclusion criteria include age ≥ 12 years old, histological confirmation of astrocytoma (absence of 1p/19q codeletion), WHO grade 3, presence of any IDH mutation, plan for radiation and chemotherapy and surgery within 6 months. The presence of CDKN2A/B homozygous deletion, spinal or leptomeningeal disease, as well as prior chemotherapy, cranial irradiation or IDH inhibitor therapy, is exclusionary. 408 patients will be randomized 1:1 to receive vorasidenib 40 mg or placebo daily with 12 cycles of temozolomide following radiotherapy and then continued as monotherapy until disease progression or unacceptable toxicity. Stratification factors include age (< 40 years old vs ≥ 40 years old) and residual disease (< 2 cm vs ≥ 2 cm). Tumor assessments with MRI will be every three months for the first two years, every four months for the next two years and then every six months thereafter as per blinded independent central review using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. Key secondary endpoints include PFS by local review, time to next treatment, safety and tolerability, quality of life measures. Exploratory measures will include seizure frequency. The trial will have 85% power to detect a hazard ratio of 0.625 with one-sided type I error rate of 0.025. Enrollment for the trial commenced February 2026. Support: U10CA180821, U10CA180882, U24CA196171. https://acknowledgments.alliancefound.org.

12010 Background: BWEL (Alliance A011401; NCT02750826) is a Phase III trial that randomizes patients (pts) with stage II-III breast cancer and body mass index (BMI) ≥27 kg/m 2 1:1 to a 24-month (mo) lifestyle-based WLI + health education (HE) or HE alone. Here we report prespecified secondary outcomes of the impact of the WLI on patient-reported QOL and symptoms. Methods: The first 540 BWEL pts (randomized between 9/2016 and 7/2017) were included in this substudy that collected PROMIS 29 Profile 2.0 and Global Health scores at enrollment, 6 and 24 mos. Adjusting for baseline scores, mean physical function (predefined substudy primary outcome), global physical and mental health, fatigue and other scores were compared at 6 and 24 mos using analysis of covariance (ANCOVA). P-values <0.05 were considered significant. Positive differences in positive attributes (e.g., physical function) and negative differences in negative attributes (e.g., anxiety) represented better outcomes in the WLI arm. Results: At baseline, median BMI was 32.9 kg/m 2 (26.5 – 69.1), median age was 53 (25 - 78) years; 83.9% of pts were non-Hispanic White, 10.7% were Black and 5.9% were Hispanic. At 6 mos, the WLI (vs HE) arm had significantly better physical function (ANCOVA-based mean difference between arms 1.9 [95% CI 0.8, 3.0]; p<0.001), global physical health (2.0 [95% CI 0.9, 3.0]; p<0.001), global mental health (1.30 [95% CI 0.2, 2.4], p=0.03), social roles and activities (2.3 [95% CI 1.1, 3.6]; p<0.001), and fatigue (-1.7 [95% CI -3.1, -0.4], p=0.01) (Table). Improvements were generally maintained at 24 mos. Similar findings were seen in analyses using longitudinal mixed modeling. Conclusions: The BWEL WLI demonstrated QOL benefits for patients with breast cancer, resulting in significantly better physical function, global physical and mental health, and symptoms. Future analyses will evaluate which populations experienced the most benefit, as well as the relationships among QOL, symptoms, and weight loss. Support: U10CA180821, U10CA180882, UG1CA189823; U10CA180820; U10CA180868; U10CA180863, CCS 707213; U10CA180888; UG1CA189858; https://acknowledgments.alliancefound.org. Clinical trial information: NCT02750826 . Analysis of covariance-adjusted least squares means values at 6-mos adjusted for baseline scores. QOL/Symptom Attributes HE WLI Between arm difference (95% CI)* P value Physical Function 47.1 49.0 1.9 (0.8, 3.0) <0.001 Global Physical Health 46.2 48.1 2.0 (0.9, 3.0) <0.001 Global Mental Health 48.6 49.9 1.3 (0.2, 2.4) 0.03 Social Roles and Activities 52.7 55.0 2.3 (1.1, 3.6) <0.001 Anxiety 50.2 50.0 -0.2 (-1.6, 1.2) 0.77 Depression 47.5 47.5 -0.0 (11.2, 1.2) 0.96 Fatigue 50.6 48.9 -1.7 (-3.1, -0.4) 0.01 Sleep Disturbance 51.0 51.1 0.1 (-0.6, 0.8) 0.80 Pain Interference 51.3 50.3 -1.0 (-2.4, 0.4) 0.15 *Positive differences in positive attributes and negative differences in negative attributes favor WLI arm.

PURPOSE Remote symptom monitoring using patient-reported outcomes (PROs) has been shown to improve symptom control and physical function among patients with advanced cancer. However, it is unclear whether these benefits are similar across demographic groups. This exploratory analysis of the PRO-TECT trial examined whether the effects of electronic symptom monitoring varied by race, age, sex, and educational attainment. METHODS PRO-TECT was a cluster randomized trial conducted across 52 US community oncology practices comparing weekly electronic symptom monitoring with usual care (UC). Adult patients with metastatic solid tumors receiving systemic therapy were enrolled (N = 1,191). Participants in the PRO arm completed weekly symptom surveys including the PRO-CTCAE, triggering alerts to the care team for severe or worsening symptoms. Patients chose whether to complete weekly PROs online or via telephone-based interactive voice response not requiring Internet access. Outcomes were measured using the European Organisation for Research and Treatment of Cancer QLQ-C30 symptom control and physical function scales. Subgroup analyses were performed by race (Black v White), age (<65 v ≥65 years), sex (male v female), and educational attainment (≤high school v >high school). RESULTS From baseline to 3 months, PRO participants showed greater improvements in symptom control (+2.37 v −0.20, P = .002) and physical function (+1.54 v −0.93, P = .02) versus UC. Benefits were most pronounced among younger, female, Black, and less educated participants. Black participants in the PRO arm were more likely to report that symptom reporting made them feel more in control of their care compared with White participants. CONCLUSION Electronic symptom monitoring improved quality-of-life outcomes overall, including among groups who have historically experienced higher symptom burden or barriers to communication. Remote PRO systems may represent an equitable strategy to enhance cancer care delivery.

PURPOSE There is growing scientific interest in incorporating patient-reported outcomes (PROs) in early phase dose-finding oncology trials (DFOTs) to assess tolerability, inform dose selection, and guide later stage trial design. However, research indicates that PRO objectives in DFOTs are often unclear. The Incorporating Patient-Reported Outcomes in Dose-Finding Trials-Research Objectives Recommendations (OPTIMISE-ROR) project was established to support trialists to effectively incorporate PROs into DFOTs. METHODS Using the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework, guideline development included the following: (1) a methodological review of published DFOTs incorporating PROs; (2) candidate item generation, refined through expert consultation; (3) a two-round international multistakeholder Delphi survey (N = 109 in Round 1 [October 2024]; N = 96 in Round 2 [December 2024]); and (4) an independently chaired virtual consensus meeting (N = 31; January 2025) where multidisciplinary, international experts reviewed and voted to finalize items for inclusion. RESULTS Consensus was reached on six recommendations emphasizing three core PRO tolerability concepts: overall side effect impact, symptomatic adverse events, and overall health-related quality of life. The integration of PROs to inform final dose recommendations in dose escalation and optimization trials should be considered, regardless of trial design. The recommendations highlight the importance of PRO data analysis over time and across dose levels, defining PRO research objectives as descriptive or statistically powered, and assessing PRO-related end points to guide end point selection for subsequent studies. CONCLUSION This foundational guidance outlines key PRO research objectives in DFOTs. By facilitating the systematic integration of PROs, this guidance supports the utilization of patient-centered evidence for the tolerability and efficacy assessment of therapies to inform dose escalation, optimization, and regulatory evaluation—ultimately contributing to the development of safer, more effective therapies.

Background: The PRO-CTCAE provides patient-reported data on symptomatic AEs. A summary metric—the ACS—reflecting total AE burden can be calculated by averaging AE-level composite scores at a given timepoint for each participant. This study investigated the psychometric properties and interpretability of this PRO-CTCAE ACS in patients with breast, lung, or head/neck cancers. Methods: We conducted a secondary analysis of a PRO-CTCAE validation dataset comprising 940 adults undergoing chemotherapy or radiation therapy (clinicaltrials.gov: NCT02158637). We focused on empirically recommended symptom terms for three cancer sites. Analyses included Spearman’s correlations, coefficient alpha, and eigenvalues from the correlation matrices, confirmatory factor analysis (CFA), and principal component analysis (PCA). Latent profile analysis (LPA) was used to assess ACS interpretability in the lung cohort. Results: Mean composite score inter-correlations were moderate (0.30–0.35), and coefficient alphas were high (0.81–0.91). Eigenvalue ratios and CFA supported retention of a single factor/component, with suitable model fit indices. ACS correlated highly with factor scores and the first principal component from the PCA. Reduced sets of terms produced reliable scores that closely approximated the full set scores and aligned with external criteria. LPA in the lung subgroup identified four latent classes; ACS differentiated high vs. low symptom burden groups but did not distinguish the two groups expressing distinct symptom profiles. Conclusion: The ACS demonstrated structural validity through adequately fitting linear factor models and effectively summarized symptomatic AE burden. However, similar ACS values may mask clinically distinct symptomatic AE profiles, underscoring the value of both summary metrics and profile-based approaches.

Abstract The Patient‐Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO‐CTCAE) was developed by the US National Cancer Institute to allow patients to directly report their side effects, enhancing the accuracy and patient‐centeredness of cancer clinical trial adverse event reporting. Clinician‐based reporting often misses the full range of patient symptoms, resulting in underreporting of side effects. The selection of adverse events for patient reporting must be defined in advance and consistently applied across all study arms. Investigators can use core symptom sets, including diarrhea, fatigue, and nausea, alongside tailored items specific to the treatments being studied. PRO‐CTCAE has demonstrated similar scores across electronic, paper‐based, and automated telephone administration methods. PRO‐CTCAE administration typically occurs before start of treatment and regularly throughout treatment, with the administration frequency tailored to the expected trajectory of side effects. Ensuring high survey completion rates is essential for PRO‐CTCAE success. Standard reporting can include tabular reporting of the proportion of patients with any (score ≥1) and high (score ≥3) levels of symptoms at the individual item level. A baseline‐adjustment approach should be applied to account for symptoms before start of treatment to isolate treatment‐emergent adverse events. The distribution of PRO‐CTCAE scores at each time point can be visualized using stacked bar charts. PRO‐CTCAE integration into cancer clinical trials is crucial for capturing a comprehensive range of treatment‐related symptomatic adverse events and improving the evaluation of therapy tolerability. Ongoing research continues to refine its implementation, supported by regulatory guidance.

PURPOSE Many trials ask patients to complete patient-reported outcome measures (PROMs) via the web, excluding patients unable to use/access the Internet. The PRO-TECT trial (AFT-39, ClinicalTrials.gov identifier: NCT03249090 ) also offered a telephone interface option (interactive voice response [IVR]). We compared patients choosing IVR versus web on alert rates to nurses and clinical outcomes to determine if a telephone option can close disparities in symptom management. METHODS PRO-TECT randomized 26 community oncology practices to the PROM intervention arm where concerning symptoms generated automated alerts to nurses. IVR and web patients were compared for social determinants of health (SDOH) using analysis of variance and chi-square tests. After accounting for clustering and confounders, we used generalized estimating equations to compare alert rates, mixed models for quality of life (QOL) at 3 months, and Cox regression for emergency visits and survival at 12 months. RESULTS Among 593 patients, 215 (36%) chose IVR and 378 (64%) chose web. IVR patients were older (65.2 v 60.8 years) and were more often rural residents (32% v 23%), Black (27% v 11%), and with less education (54% v 27% ≤high school; all P < .01). Patients choosing IVR had more surveys with concerning symptoms (49% v 37%) and nurses felt clinical attention was warranted more often (4.8 surveys v 3.4 surveys; all P < .001) but ultimately experienced similar benefits as web in QOL, emergency visits, and survival. CONCLUSION One third of community patients choose a telephone option over the web for reporting PROMs during cancer care. These patients are disproportionately from SDOH backgrounds at risk of poor clinical outcomes and have higher symptom management needs but ultimately experience similar clinical benefits as patients choosing the web. PROM programs should offer web alternatives to close disparities in symptom management.

PURPOSE Monitoring with electronic patient-reported outcome (ePRO) systems can improve cancer outcomes and is increasingly recommended. Optimal implementations of ePROs in routine clinical care are not yet known. Perspectives from clinicians, clinic staff, and patients who used ePROs can provide real-world insights for optimizing the design, efficiency, and effectiveness of future implementations. METHODS Providers, clinic staff, and patients receiving treatment for metastatic cancer from community oncology practices that implemented ePROs as part of the national PRO-TECT trial (Alliance AFT-39) participated in semi-structured interviews related to ePROs. Perceptions from clinicians on perceived benefits, usefulness, acceptability, impact on quality of care, and required effort; from staff on clinical integration and effort; and from patients on ease of use, usefulness, and effort were collected. Themes, subthemes, and recommendations were identified via a standardized coding-based directed thematic analytic approach. RESULTS Ninety-eight clinic members and 67 patients participated from 25 intervention sites. Four themes were identified: (1) positive impact of ePROs on cancer care quality, communication, and relationship-building; (2) ePRO system usability; (3) challenges to ePRO integration with clinical workflow; and (4) recommendations for improving ePRO systems and implementation. Subthemes related to the impact of ePROs on cancer care included enhanced communication with care team, increased awareness of symptoms, and increased ability to self-manage symptoms. Actionable recommendations for future initiatives were to engage and train clinicians, staff, and organizational support for ePRO-related activities; tailor content of ePRO surveys to be clinically actionable; integrate ePRO alert notifications and reports with existing information systems; and optimize integration of ePROs with existing clinic workflow processes. CONCLUSION Experiences of care team members and patients were positive, with actionable recommendations identified to guide future ePRO implementations.