Abstract: e19173 Background: Unreported symptoms during cancer treatment can lead to poorer patient care and quality of life. eHealth technologies enable effective means to track patients’ health in real time to provide assistance in meeting patients’ needs and facilitating symptom management. Methods: Gynecologic (endometrial and ovarian) and breast oncology patients were enrolled in a quality improvement program post-surgically to respond to 12-monthly, text-based symptom surveys assessing fatigue, sleep quality, pain, and depression (PHQ-9). At baseline, 6 and 12 months, patients also completed the PROMIS-10 to assess their physical and mental health functioning. All patient responses were captured in REDCap and monitored by program staff, with patients’ oncologists receiving monthly feedback for patient follow-up. Patient navigators were also engaged for patients needing assistance with non-medical concerns. We provide the interim results of this program on PROMIS-10 scores from baseline to 6 months. Results: 198 breast and 120 gynecologic oncology patients (ovarian [n = 70] and endometrial [n = 50] ) were enrolled. Multiple regression examined the impact of demographic (age, race, education), clinical (stage, chemotherapy, radiation), and monitoring program variables (# of monthly surveys completed, navigation services [yes/no]) on PROMIS-10 physical and mental health subscale scores at 6 months, adjusting for baseline PROMIS scores. For the breast patients, the only significant predictor of worse PROMIS physical health scores was a cancer stage of 4 vs 1 (p = 0.049), whereas a higher number of symptom surveys completed was associated with worse mental health functioning (p = 0.033). For the gynecologic oncology patients, worse PROMIS physical health scores were only associated with higher age (p = 0.037), but higher PROMIS mental health was also associated with higher age (p = 0.029) and borderline significantly associated with not using navigation services (p = 0.07). Conclusions: These results indicate that greater adherence in completing monthly symptom surveys and using navigation services were more likely to be associated with patients reporting lower mental health. PROMIS physical health scores, however, were not significantly associated with adherence to monthly surveys or navigation services. These interim results suggest that monitoring programs, such as this, may assist in identifying and treating patients with lower mental health functioning during treatment.

Abstract: 2051 Background: Cognitive problems after cancer therapy can decrease QOL. This phase III randomized trial tested the effect of donepezil (5-10 mg daily for 24 weeks) on cognition and QOL in brain cancer patients. Methods: Between 2/2008-12/2011, 198 (99 placebo; 99 donepezil) adult primary and metastatic brain tumor survivors 〉 6 months post radiation ( 〉 30 Gy) were recruited at 24 sites affiliated with the Wake Forest CCOP Research Base, 3 CTSU sites, and M.D. Anderson. Outcomes were assessed at baseline, 12 and 24 weeks. Regression analyses examined the association of demographics, fatigue (FACIT-Fatigue), and a cognitive performance composite score (CC) (comprised of the Controlled Oral Word Association Test, Hopkins Verbal Learning Test-Revised, Digit Span Test, Trail Making Test A & B, Rey-Osterreith Complex Figure-modified, Grooved Pegboard) on QOL, measured by the FACT-Brain (FACT-Br) total score. Results: Participants had a median age of 55, were predominantly female (54%) and non-Hispanic White (91%), with a median time from diagnosis of 38 months. Study completion was 74%. At 12 and 24 weeks, treatment had no significant effect on QOL, unadjusted and adjusted for race/ethnicity, age, sex, fatigue, baseline FACT-Br, and baseline CC. However, for those below the median on the baseline FACT-Br subscale (i.e., greater cognitive symptoms), donepezil was associated with higher (better) post-tx FACT-Br total scores (p =0.004), unadjusted for covariates. After adjustment for covariates, donepezil was borderline significantly associated with higher post-tx QOL (p=0.052). Improvement in QOL was associated with being female (p=0.017) and less baseline fatigue (p=0.005). For participants with baseline FACT-Br subscale scores above the median, only lower baseline FACT-Br total scores (p=0.015) were significantly related to greater improvements in FACT-Br. Donepezil treatment was not significant (p=0.48). Conclusions: The impact of donepezil on QOL was greater in survivors with more cognitive symptoms at baseline, although the results were borderline significant. Fatigue continued to be a major factor in lower QOL. Other interventions to better manage survivors’ symptoms are needed. Clinical trial information: NCT00369785.

Abstract: 9505 Background: Armodafinil (ARM), the R-enantiomer of modafinil, is FDA approved for narcolepsy, shift work disorder, and treated sleep-apnea, and has also been shown to reduce fatigue/improve cognitive function in cancer patients. This phase II study estimated the efficacy and toxicity of ARM in primary brain tumor (PBT) patients receiving brain radiation therapy (RT) to determine whether a larger phase III study would be warranted. Methods: Eligibility criteria – adult, PBT, total RT dose 〉 45Gy, KPS 〉 60, no severe headaches, and concurrent chemotherapy allowed. Patients were assessed at baseline, end of RT, then 4 weeks after end RT with the Brief Fatigue Inventory (BFI), Epworth Sleep Scale (ESS), FACT, and FACT brain and FACIT fatigue subscales. Patients were randomized to receive ARM 150mg/day during RT and for 4 weeks after RT or placebo (PLAC). Results: 54 patients enrolled between 9/10-12/12; 26 to ARM, 28 to placebo PLAC. Median age 59; 59% female; 95% White; 41% KPS 90-100, 59% KPS 60-80; 74% malignant glioma, 26% low-grade glioma/benign histology. 83% patients had concurrent chemotherapy. For all randomized patients, there were no statistically significant differences in outcome between ARM and PLAC groups at end-RT vs. baseline or 4 weeks post RT vs. baseline. For patients who had more baseline fatigue (fatigue subscale score 〈 median), ARM-treated patients had significantly/suggestively better outcomes at end-RT vs. baseline compared to PLAC-treated patients: less fatigue (BFI p=0.056, fatigue subscale p=0.0295), less sleepiness (ESS p=0.1034), and better QOL (FACT p=0.0001). Incidence of grade 2/3 toxicities was the same between the two treatment groups: 7% anxiety, 7% nausea, 18% headaches, and 20% insomnia. There were no grade 4 or 5 toxicities. Conclusions: In irradiated PBT patients, fatigue, sleepiness, and reduced QOL occurring at the end of brain RT was less with ARM in those patients who were more fatigued at baseline. Toxicity was minimal. These data support conducting a larger phase III study. Analysis of cognitive function data is ongoing. Support - NIH/NCI grant 2U10 CA 81851 and Teva Pharmaceuticals. Clinical trial information: 95709.

Abstract: 68 Background: Accrual of racial and ethnic minority patients (pts) to clinical trials has been an ongoing challenge in research. Barriers exist at many levels of engagement including trial availability, screening biases, strict enrollment criteria, and structural racism. Lack of trial diversity has led to less generalizable medical evidence, suboptimal data for toxicity and efficacy of cancer treatments, poorer outcomes and continued mistrust by communities of color in research processes that exclude or marginalize them. Site factors and study design strategies associated with successful recruitment of diverse study populations are understudied. Methods: Alliance A191901 is an RCT testing combinations of text and telephone support to promote endocrine therapy adherence among breast cancer survivors. It oversamples Black participants and those 〈 50 years at thresholds of 30% each. Administrative enrollment data was used to track and describe monthly accrual trajectory by race among the initial 50% of participants (n = 590) and to examine associations between % Black participants accrued and accruing site characteristics, including site type, geographic region, % Black population in the site’s zip code and volume of pts by race accrued to recent (2018-2019) Alliance trials, using χ 2 tests. We also examined patterns of Black participant accrual before and after closure of the A191901 study to non-Black participants. Results: At 50% accrual, 124 sites had enrolled at least 1 participant. Among 590 participants, 9.7% were Black and 22.5% were 〈 50 years. Neither site type nor volume was associated with % Black participants recruited. Sites in the South recruited higher proportions of Blacks (19.0% vs 5.6% for Midwest, the lowest region, p 〈 0.001). Neighborhood racial composition was positively associated with accrual of Black participants (17.2% at sites from highest Black composition vs. 2.3% in lowest, p 〈 0.001). Recruitment trajectories of Black participants consistently lagged those of non-Black participants in the first half of the study; however, Black participants recruited per month numerically increased after the study reached target accrual of non-Blacks and closed to non-Black participants. Conclusions: Sites in neighborhoods and geographic regions with larger Black populations recruited higher proportions of Black participants, but site type and volume were not associated with recruitment of Black participants. Closure of non-Black study strata based on predetermined accrual targets may positively impact recruitment trajectories of Black participants, but further study is needed. Site selection based on neighborhood composition and geography may be an appropriate tool for increasing trial diversity. Support: UG1CA189823. Clinical trial information: NCT04379570.

Abstract: Background: Quality of life (QOL) in breast cancer patients (pts) can be greatly impacted by initial treatment and ongoing therapy, particularly if side effects and symptoms are not well tolerated. The PALLAS trial investigated whether the addition of 2 years of palbociclib (palbo) to adjuvant endocrine therapy (ET) improved invasive disease-free survival (iDFS) over adjuvant ET alone. We report on the main patient-reported outcome (PRO) quality of life (QOL) and symptom severity results of this trial by treatment arm. Methods: PALLAS is an ongoing multicenter, open label phase 3 trial that enrolled hormone receptor positive, HER2-negative, stage II-III breast cancer patients at 406 cancer centers across 21 countries. Patients were randomly assigned (1:1) to either 2 years of palbo (125mg/day, 3 weeks on 1 week off) plus ongoing provider or patient-choice adjuvant ET (palbo+ET) versus ongoing ET alone. The primary study endpoint was iDFS. Treatment with palbo in all pts stopped at the time of the second interim analysis (5/2020) due to futility; all pts then moved to follow up. The PRO analyses were triggered for completion after awareness of the pre-specified 469 iDFS cases in November 2020. Eight PRO endpoints were measured serially (i.e., day 1 of each monthly cycle for the first 3 months, then every 3 months for the first 2 years, and once at year 3). The endpoints were the EORTC QLQ-C30 global health status/QOL score, the Brief Fatigue Inventory score, the modified Brief Pain Inventory severity and pain interference scores, the EORTC QLQ-BR23 alopecia score, and the Breast Cancer Prevention Trial hot flash symptoms, vaginal problems, and musculoskeletal pain scores. Linear mixed models compared the average difference between arms across time points during the initial 2-year treatment period adjusting for cycle 1 day 1 (C1D1) PRO scores, demographic and clinical variables. The average differences between arms (palbo+ET vs ET alone) and the two-sided (1-[0.05/8]) x 100% confidence intervals, adjusted for multiple comparisons, were calculated. Analysis of covariance compared the average between-arm differences by endpoint at 3 years. Results: The PRO intention to collect population included 4688 (81%) of the overall trial pts, and was clinically and demographically representative of the remaining 1073 pts. Each analysis population, with measures at C1D1 and at least 1 post-C1D1 assessment for each PRO endpoint, comprised ≥ 89% of the 4688 pts and the proportions were similar between arms. After adjustment for baseline covariates, on average, no clinically important differences between arms were observed for any of the eight endpoints over the 2 year treatment period (Table 1). All effect sizes were below the pre-specified 0.2 threshold. These PRO results were similar at the 3 year time point. Conclusions: No clinically significant differences in either patient-reported QOL or symptom severity were found, on average, between participants in the two PALLAS treatment arms while either taking palbo+ET or ET alone, or after study-wide termination of palbo. In general, the addition of palbociclib in the adjuvant breast cancer setting did not contribute to increased symptom burden within this survivorship population. Further analyses will examine the relationship between PROs and treatment discontinuation by arm and study time point. Support: AFT, Pfizer, https://acknowledgments.alliancefound.org Table 1.Results of the Patient-Reported QOL and Symptom Severity Analyses Between the Two Treatment Arms During the First 2 Years of PALLASPRO Endpoint *Palbo + ET Adjusted average score (95% CI)ET alone Adjusted average score (95% CI)Average Difference + (Palbo + ET vs ET alone)[99.38% CI] Clinically ++ Important DifferenceEORTC QLQ-C30 Global Health Status/QOL71.7 (71.2, 72.2)74.0 (73.5, 74.5)-2.3 (-3.3, -1.4)**NoBrief Fatigue Inventory Score2.3 (2.2, 2.3)2.1 (2.0, 2.1)0.2 (0.1, 0.3)NoModified Brief Pain Inventory - Severity Score2.3 (2.2, 2.3)2.4 (2.4, 2.5)-0.2 (-0.3, -0.1)NoModified Brief Pain Inventory - Interference Score1.7 (1.6, 1.7)1.7 (1.6, 1.7)0.0 (-0.1, 0.1)NoEORTC QLQ-BR23 Alopecia1.4 (1.4, 1.4)1.3 (1.3, 1.3)0.1 (0.1, 0.1)NoBreast Cancer Prevention Trial - Hot Flash Symptoms1.2 (1.2, 1.3)1.2 (1.2, 1.3)0.0 (-0.1, 0.1)NoBreast Cancer Prevention Trial - Vaginal Problems0.8 (0.8, 0.8)0.8 (0.7, 0.8)0.0 (0.0, 0.1)NoBreast Cancer Prevention Trial - Musculoskeletal Pain1.2 (1.2, 1.2)1.3 (1.3, 1.3)-0.1 (-0.2, 0.0)No* For the EORTC QLQ-C30 Global Health Status/QOL subscale, higher scores indicate better QOL. For all other PRO endpoints, higher scores indicate worse symptom levels. ** The lower bound of the one-sided CI (adjusted for multiple comparisons) was -3.3. Because the lower limit is greater than the pre-specified non-inferiority margin of -3.44, non-inferiority of palbo+ET relative to ET-alone was concluded. The non-inferiority margin corresponds to a 0.2 SD in the EORTC QLQ-C30 global health/QOL score. +The average difference was adjusted for the following baseline covariates: Cycle 1 day 1 score, region (if applicable), age category, first adjuvant ET, race, ethnicity, N-stage, T-stage, histological grade, PgR, prior chemotherapy, ECOG Performance Status. ++Based on each instrument’s published clinically relevant cut-offs, if available. After calculating Cohen’s d treatment effect sizes, (i.e. by dividing the average difference by the ET-alone arm standard deviation from cycle 1 day 1), all effect sizes were below the pre-specified 0.2 threshold, and would not be considered clinically important. Citation Format: Michelle Joy Naughton, David Zahrieh, Michael Gnant, Nicholas Zdenkowski, Julie Lemieux, Jun J Mao, Vesna Bjelic-Radisic, Eileen Shinn, Marija Balic, Christoph Thomssen, Jane Neisel, Manuel Ruiz-Echarri, Sibylle Loibl, Claudine Isaacs, David Cameron, Fernando Manuel Henao Carrasco, Matthew Goetz, Viktor Wette, Gustavo Werutsky, Hope Rugo, Marcus Vetter, Ling-Ming Tseng, Kathy Miller, Florian Fitzal, Juan Miguel Gil Gil, Haeseong Park, Barbro Linderholm, Emilio Bajetta, Zoneddy Dayao, Aleix Prat, Karin Ehrhardt, Otto Metzger, Amal Arahmani, Ernest Law, Ann Partridge, Lisa Carey, Alex Zoroufy, Amylou Dueck, Dominik Hlauschek, Angela DeMichele, Erica Mayer. Quality of life and symptom severity in the PALLAS randomized trial of palbociclib with adjuvant endocrine therapy in early breast cancer (AFT-05) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-01.

Abstract: 3611 Background: CALGB 80405, a phase III trial, was originally designed to compare toxicity and overall survival of metastatic colorectal patients treated with standard chemotherapy (choice of FOLFOX or FOLFIRI) and either: 1) Bevacizumab; 2) Cetuximab; or 3) both Bevacizumab and Cetuximab. Because Cetuximab causes a prominent acneiform skin rash, adverse effects on QOL were anticipated and assessed in a QOL companion. Methods: The QOL companion enrolled the first 518 consenting patients randomized to CALGB 80405 between 10/2005-9/2007, the majority prior to amendments that eliminated the dual biologic arm and restricted participation to patients with KRAS wttumors. QOL was assessed at baseline, 6 weeks, and 3, 6 and 9 months post-randomization, using the EORTC QLQ-30 and the Dermatology-Specific Quality of Life (DSQL) Scale. We hypothesized that patients receiving Cetuximab would have lower satisfaction with appearance, reduced social functioning and lower overall QOL at 3 months, (a primary assessment point). Results: Patients had a mean age of 59, were predominantly male (58%), performance status 0 (62%), and non-Hispanic White (85%). 83% completed a 3 month assessment. There were no differences in global health functioning (p=0.164) or other items/subscales of the EORTC at 3 months by treatment arm. However, significant differences were found across arms in skin symptoms (p 〈 .0001), limitations in social activities due to skin condition (p=0.008), and concerns about appearance (p 〈 .0001), as measured by the DSQL. Patients randomized to Bevacizumab reported fewer skin symptoms, fewer social limitations and appearance concerns than patients receiving Cetuximab alone or Cetuximab + Bevacizumab. The choice of chemotherapy (FOLFOX or FOLFIRI) had no bearing on these results. Conclusions: Global QOL, as well as physical, role, social and emotional functioning, were not significantly different across treatment arms. However, Cetuximab recipients reported greater symptoms and QOL concerns relating to their skin than those receiving Bevacizumab alone. Interventions to more adequately address skin problems from Cetuximab treatment are warranted. Participants are still being followed to determine survival differences between the biologics. Clinical trial information: NCT00265850.

Abstract: 9108 Background: Fatigue can be measured with different validated assessment instruments in symptom management trials. Methods: Between 2004-2009, the Wake Forest CCOP Research Base protocol 97202 randomized 236 women receiving adjuvant chemotherapy for newly diagnosed breast cancer to Coenzyme Q10 supplementation vs placebo. The primary endpoint was change in self-reported fatigue. Patients (pt) were assessed at baseline, 8, 16, and 24 weeks (wk) with 3 instruments: 1) Profile of Mood States – Fatigue (POMS; 7 questions; scored 0-4); 2) Functional Assessment of Cancer Treatment – Fatigue (FACIT; 13 questions; scored 0-4); and 3) Visual Analog Scale (VAS; one scale; scored 0-10). For comparison, each instrument was rescaled from 0 to 100; higher numbers indicate worse fatigue. Results: CoQ10 did not significantly affect fatigue (Lesser G et al, ASCO Proc., 2010). All 3 measures demonstrated an increase in fatigue after chemotherapy initiation at 8 & 16 wks with trend towards baseline levels at 24 wks. The fatigue measures were highly correlated: r ≥ 0.8 for all pairwise associations at all times. However, their scores varied. The Table shows mean rescaled scores for pt below/above the median fatigue level, calculated by taking mean of the three scores averaged across the four time periods. In general, POMS tended to give the lowest and VAS the highest scores, but differences between POMS and FACIT and FACIT and VAS depended on mean fatigue level. For pt experiencing lower ( 〈 median) fatigue, FACIT and VAS scores were similar, while POMS scores were significantly lower. For higher ( 〉 median) fatigue, POMS and FACIT scores were similar, while VAS was significantly higher. Conclusions: While POMS, FACIT, and VAS scores were highly correlated, their scale scores varied depending on the level of fatigue experienced by the pt. Fatigue assessment methods in clinical trials should be selected carefully as they do not always give equivalent results. Supported by NCI/DCP grant U10 CA81851. [Table: see text]