Functional Assessment Of Cancer Therapy-Prostate Research Articles

Patient-reported Quality of Life and Survival Outcomes in Prostate Cancer: Analysis of the ECOG-ACRIN E3805 Chemohormonal Androgen Ablation Randomized Trial (CHAARTED)

BackgroundChemohormonal therapy with androgen deprivation therapy and docetaxel (ADT + D) improves overall survival (OS) and quality of life (QOL) at 12 mo versus androgen deprivation therapy (ADT) alone in men with metastatic hormone-sensitive prostate cancer (mHSPC). However, the prognostic role of QOL is unknown in this population. ObjectiveTo study the relationship between QOL, disease characteristics, and OS in men with mHSPC. Design, setting, and participantsIn this exploratory post hoc analysis, 790 patients with mHSPC completed the QOL instruments Functional Assessment of Cancer Therapy—Prostate (FACT-P), Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT-F), and Brief Pain Inventory (BPI). Outcome measurements and statistical analysisLog-rank test and Cox proportional hazard models tested the association between QOL and OS by clinical and disease characteristics. Results and limitationsBaseline higher FACT-P trended toward improved survival after accounting for clinical variables (hazard ratio [HR] 0.80 [0.62, 1.04], p = 0.09), while higher 3-mo FACT-P was independently associated with better survival (HR 0.76 [0.58, 1.0], p = 0.05). Patients with the poorest QOL (bottom quartile) at baseline and 3 mo had longer survival if they received ADT + D rather than ADT alone (median OS 45.2 vs 34.4 mo, HR 0.75 [0.53, 1.05], p = 0.09, and 48.3 vs 29.3 mo, HR 0.69 [0.48, 0.99], p = 0.05 respectively). In contrast, patients with the best QOL (top quartile) at baseline and 3 mo had comparable survival irrespective of whether or not docetaxel was added (median OS 72.1 vs 51.7 mo, HR 0.92 [0.63, 1.36], p = 0.69, and 69.9 vs 68.9 mo, HR 1.11 [0.73, 1.67], p = 0.63, respectively). Survival was linked with baseline FACIT-F (HR 0.76 [0.57, 1.0], p = 0.05), but not BPI (HR 0.98 [0.75, 1.28], p = 0.90). ConclusionsThree-month QOL had a stronger independent association with survival. The most symptomatic patients had longer survival with the addition of docetaxel; conversely, the least symptomatic patients did not appear to benefit. Consideration of QOL may enhance decision-making and patient selection when choosing chemohormonal treatment in mHSPC. Patient summaryQuality of life independently forecasted the survival of men with metastatic hormone-sensitive prostate cancer in the CHAARTED study. Close tracking of quality of life could help patients and clinicians make decisions about the appropriate treatment in this setting.

Patient-reported outcomes (PRO) in patients (pts) with BRCA1/2-altered metastatic castration-resistant prostate cancer (mCRPC) receiving niraparib (NIRA) with abiraterone acetate and prednisone (AAP): Results from MAGNITUDE study.

105 Background: MAGNITUDE, an international phase 3 randomized double-blind study, demonstrated that mCRPC pts with BRCA1/2 alterations receiving NIRA + AAP had significantly improved radiographic progression-free survival, and clinically relevant prolongations in time to symptomatic progression and time to cytotoxic chemotherapy compared with placebo (PBO) + AAP. Here, we report PRO results (pain, health-related quality of life [HRQoL], and side effect bother) in the BRCA1/2 subset of mCRPC pts in the final analysis of MAGNITUDE. Methods: Pts were screened prospectively for homologous recombination repair (HRR) gene alterations. Eligible pts had ECOG status ≤1 and a Brief Pain Inventory–Short Form (BPI-SF) worst pain score ≤3 (scale of 0-10), and were randomized 1:1 to NIRA + AAP or PBO + AAP orally daily in 28-day cycles. PRO assessments on day 1 of specified cycles included BPI-SF and Functional Assessment of Cancer Therapy–Prostate (FACT-P). Time to deterioration (TTD) in pain (BPI-SF worst, average, and pain interference, and FACT-P pain-related scale [PRS]) were compared between treatment arms using proportional hazards regression models. Changes from baseline in HRQoL (FACT-P total, scale of 0-156) were compared using repeated measures analysis, and side-effect bother was assessed in both arms as a single item from FACT-P (GP5). Results: PRO compliance for FACT-P and BPI-SF was >85% in 225 pts with BRCA1/2-altered mCRPC. At baseline, mean BPI-SF pain scores was 1.09 (SD, 1.57) in NIRA + AAP and 1.35 (SD, 1.98) in PBO + AAP. Mean FACT-P Total in NIRA + AAP and PBO + AAP was 116.33 (SD, 18.42) and 114.8 (SD, 18.9), respectively. Median TTD in BPI-SF worst pain, pain interference, average pain, and FACT-P PRS were numerically longer for NIRA + AAP vs. PBO + AAP (Table). Repeated measures results showed HRQoL was maintained on treatment for the BRCA subgroup with no clinically meaningful differences in the FACT-P total score over time or between treatment arms. Analysis of FACT-P item GP5 in the BRCA subset showed side effect bother was rated “not at all” or “a little bit” by 87% of NIRA + AAP and 92% of PBO + AAP subjects across treatment cycles. Conclusions: In pts with BRCA1/2-altered mCRPC, NIRA + AAP maintained HRQoL. Pts experienced minimal bother from side effects associated with treatment. These data further support the benefit-risk profile of NIRA + AAP for the treatment of mCRPC pts with BRCA1/2 alterations. Clinical trial information: NCT03748641 . [Table: see text]

Post Hoc Analysis of Rapid and Deep Prostate-specific Antigen Decline and Patient-reported Health-related Quality of Life in SPARTAN and TITAN Patients with Advanced Prostate Cancer

BackgroundAdding apalutamide to androgen-deprivation therapy (ADT) resulted in a rapid (at 3- and 6-mo treatment) and deep prostate-specific antigen (PSA) decline (to ≤0.2 ng/ml or ≥90% from baseline), improved overall survival, reduced risk of disease progression, and prolonged health-related quality of life (HRQoL) in nonmetastatic castration-resistant prostate cancer (nmCRPC) in SPARTAN and metastatic castration-sensitive PC (mCSPC) in TITAN. ObjectiveTo evaluate the association of a rapid, deep PSA decline at 3 and 6 mo achieved with the addition of apalutamide to ADT with patient-reported outcomes (PROs) in SPARTAN and TITAN. Design, setting, and participantsA post hoc analysis of SPARTAN and TITAN PRO data was performed. InterventionApalutamide versus placebo plus concurrent ADT. Outcome measurements and statistical analysisPROs were assessed using Functional Assessment of Cancer Therapy-Prostate (FACT-P; SPARTAN and TITAN), Brief Pain Inventory—Short Form (BPI-SF; TITAN), and Brief Fatigue Inventory (BFI; TITAN) at baseline, prespecified cycles during treatment, and after progression for ≤1 yr. The association between a deep PSA decline at landmark 3 or 6 mo of apalutamide and the time to worsening of PROs was assessed using the Kaplan-Meier methodology and Cox proportional-hazard modeling. Results and limitationsAmong 806 SPARTAN and 525 TITAN apalutamide-treated patients, the median treatment duration was 32.9 and 39.3 mo, respectively. Patients achieving a deep PSA decline at 3 mo had longer time to worsening in FACT-P total, FACT-P physical well-being, BPI-SF worst pain intensity, or BFI worst fatigue intensity. The 6-mo PSA decline results were similar. Limitations of patient characteristics in clinical studies should be considered. ConclusionsAttaining a deep and rapid PSA decline at 3 mo with apalutamide plus ADT was associated with longer preservation of overall HRQoL and physical well-being in nmCRPC and mCSPC. Patient summaryQuality of life is maintained in individuals with advanced prostate cancer who achieve a deep prostate-specific antigen decline at 3 mo of apalutamide plus drugs that lower male sex hormones.

Patient reported quality of life (QOL) and survival outcomes: Analysis of ECOG-ACRIN E3805 chemohormonal androgen ablation randomized trial (CHAARTED) in prostate cancer (PCa).

5014 Background: Chemohormonal therapy with androgen deprivation therapy and docetaxel (ADT+D) improves overall survival (OS) and quality of life (QOL) at 12 months compared to ADT alone in metastatic hormone sensitive prostate cancer (mHSPC). However, the prognostic relationship between QOL, disease characteristics, and OS has not been described in this population. Methods: In this post-hoc exploratory analysis of the CHAARTED trial, the QOL instrument Functional Assessment of Cancer Therapy-Prostate (FACT-P) was completed by patients treated with ADT and ADT+D. Log-rank test and Cox proportional hazards models were used to test the association between QOL and OS by clinical and disease characteristics. Results: 790 men were included in the study (ADT+D, n = 397; ADT, n = 393). Baseline higher QOL by FACT-P (n = 790) was associated with better OS in univariate regression (HR 0.70 [0.55,0.90], p = 0.005), however the association was not significant in multivariate analysis (HR 0.80 [0.62-1.04], p = 0.09). There was a trend towards improved survival for patients with the lowest baseline QOL (lowest quartile) treated with ADT+D compared to ADT (HR 0.75 [0.53, 1.05], p = 0.09). In contrast, patients with the highest baseline QOL (highest quartile, 63% high volume disease) had similar survival regardless of treatment arm (HR 0.92 [0.63-1.36], p=0.69). Higher 3-month QOL by FACT-P (n = 654) was associated with survival in the multivariate analysis independently of treatment arm (HR 0.76 [0.58, 1.0], p = 0.05). Patients with the highest 3-month QOL had comparable survival regardless of treatment arm (HR 1.11 [0.73, 1.67], p = 0.63), while patients with the lowest 3-month QOL experienced a survival benefit with ADT+D compared to ADT (HR 0.69 [0.48, 0.99], p = 0.047). Conclusions: In this analysis, 3-month QOL by FACT-P was significantly associated with survival for patients with mHSPC. Patients with the poorest QOL ("most symptomatic”) appeared to experience survival benefit from ADT+D regardless of disease volume. Conversely, patients reporting the highest QOL (“least symptomatic”) did not seem to benefit from ADT+D despite a predominance of patients with high volume disease in that cohort. These findings suggest that consideration of QOL may enhance decision making and patient selection when considering chemohormonal treatment for mHSPC. [Table: see text]

Randomized placebo-controlled trial of intravenous vitamin C plus docetaxel in metastatic prostate cancer.

e17050 Background: Some phase I/II trials showed that combining high dose IV vitamin C with chemotherapies decreased toxicities and improved QoL in advanced cancers, while others failed to show benefits. While grade ¾ AEs are not typically a co-primary endpoint, they are a measure of cumulative toxicity. We investigated whether high-dose IV vitamin C could improve prostate-specific antigen (PSA) response rate and mitigate docetaxel toxicities in patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving docetaxel. Methods: Patients were randomized (2:1) to receive docetaxel (75mg/m2 IV every 3 weeks) plus IV vitamin C (1g/kg) or placebo twice a week. The primary endpoints were PSA50 response by24 weeks and adverse events (AEs) of fatigue, nausea, bone pain, and anorexia. Secondary endpoints included overall survival (OS) and QoL measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Results: 50 patients were randomized, 47 received therapy (treatment N = 32, control N = 15), 3 untreated (withdrawal, elevated creatine, low hemoglobin). The median age was 74 years (range 45-85) and ECOG 1. The median PSA was 108.3 ng/mL (range: 0.3, 2102.3). The median number of chemotherapy cycles was 6 (IQR 3-8). The study was suspended after the pre-specified interim analysis for primary endpoints showed futility. The PSA50 response was 41% for treatment and 33% for control (P = 0.44). Grade 1-2 and grade 3-4 prespecified AEs occurred in 69% and 6% of treatment group patients versus 60% and 0% of control group patients (one-sided Cochran Armitage test, P =0.90). Diarrhea (72% vs 19%) and anemia (47% vs 25%) and neutropenia (22% vs 19%) are more frequent in the Vit C group. Compared with the control group, treatment group patients showed a trend towards shorter median OS. FACT-P was not significantly different at any timepoints. Conclusions: Initial concurrent high-dose IV vitamin C with docetaxel did not improve PSA response, toxicity, or clinical outcomes. MCRPC patients receiving docetaxel should be advised against seeking concurrent high-dose IV vitamin C. Clinical trial information: NCT02516670 .

Health-related quality of life (HRQoL) and pain outcomes for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) who received abiraterone (abi) and olaparib (ola) versus (vs) abi and placebo (pbo) in the phase III PROpel trial.

5012 Background: PROpel (NCT03732820) met its primary endpoint and showed significantly prolonged investigator-assessed rPFS with abi + ola vs abi + pbo at primary analysis (data cut-off [DCO]: 7/30/21; median 24.8 vs 16.6 months (m); hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.54–0.81; P<0.001). HRQoL (based on The Functional Assessment of Cancer Therapy-Prostate [FACT-P] total score) was not different when ola was combined with standard-of-care abi. We present data at the final prespecified overall survival (OS) DCO (10/12/22). Methods: PROpel is a randomised, double-blind trial in 1L mCRPC. Time to pain progression (TTPP) was based on the Brief Pain Inventory-Short Form (BPI-SF) Item 3 ‘worst pain in 24 hours’ and opiate analgesic use (analgesic quantification algorithm) score. Time to first symptomatic skeletal related event (SSRE) was time to use of therapy to prevent/relieve skeletal symptoms, new bone fractures, spinal compression or surgery on bone metastases. HRQoL was assessed by change from baseline (BL) in FACT-P total and subscale scores, BPI-SF pain severity, pain interference and worst pain score between arms using a mixed model for repeated measures. Results: At median follow-up of 33.6 m with abi + ola and 32.1 m with abi + pbo, 17.0% pts (68/399) in the abi + ola arm and 15.1% pts (60/397) in the abi + pbo arm had pain progression (PP) events. The % of pts who had not experienced PP with abi + ola vs abi + pbo was 76.9% vs 77.2% at 24 m and 70.7% vs 71.0% at 36 m. No meaningful difference in TTPP was observed (16% maturity, HR 1.06, 95% CI 0.75–1.50, P=0.75 [nominal], median not reached [NR] either arm). The % of pts who had not had a SSRE with abi + ola vs abi + pbo was 86.1% vs 82.2% at 24 m and 80.8 vs 78.5% at 36 m. No meaningful difference in time to SSRE was observed (12% maturity, HR 0.82, 95% CI 0.55–1.22, P=0.32 [nominal], median NR vs NR). Least-squares mean changes from BL between arms in BPI-SF pain severity (difference, −0.06; 95% CI −0.23–0.12), pain interference (difference, −0.12; 95% CI −0.31–0.06), worst pain score (difference, −0.12; 95% CI −0.35–0.11) and FACT-P total score (difference, −0.54; 95% CI –3.00–1.92) suggest no clinically meaningful difference in HRQoL with abi + ola vs abi + pbo. Least-squares mean change from BL values for FACT-P subscale scores were consistent with FACT-P total score result. Conclusions: PROpel demonstrated a significant delay in rPFS for pts receiving abi + ola vs abi + pbo. Most pts in the trial did not experience a PP event. Abi + ola showed no difference in HRQoL (assessed by FACT-P total and subscale scores, BPI-SF domain and worst pain scores) vs abi + pbo, suggesting pts can derive clinical benefit from abi + ola while maintaining a similar HRQoL compared with a current standard-of-care treatment. Clinical trial information: NCT03732820 .

Effect of Serelys Homme on the Incidence and Severity of Vasomotor Symptoms and Quality-of-Life Impairments in Patients Receiving Hormone Therapy and Radiation for Localized Prostate Cancer: Results of the ESCULAPE Phase 2 Prospective Study

Androgen deprivation therapy (ADT) may cause vasomotor symptoms (VMS) including hot flushes and sweats, which affect quality of life (QoL). Serelys Homme is a nonhormonal and a natural origin product that could affect VMS in men undergoing ADT. We evaluated effectiveness and tolerance of Serelys Homme administration on VMS and QoL of patients undergoing combined ADT and radiation therapy for prostate cancer. Between April 2017 and July 2019, 103 patients were screened, and 53 patients refused to participate in the study. Serelys Homme therapy consisted of a daily administration of 2 tablets for 6 months. Patients were evaluated with 4 questionnaires including the adapted Modified Rankin Scale (adapted-MRS), European Quality of Life 5 Dimensions 3 Level Version (EQ 5D3L), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and Hot Flash Related Daily Interference Scale (HFRDIS) at day 0, day 90 (D90), and day 180 (D180). Statistical evaluation was performed using the Wilcoxon rank sign test. A 2-sided P < .05 was considered statistically significant. Among the 50 patients, 4 withdrew after inclusion. All patients (n=46) received either postoperative or definitive radiation therapy combined with a short (n=15) or long course (n=31) of ADT. Serelys Homme administration significantly decreased the rate of patients who had ≥7 VMS and 3 to 6 VMS per day. The number of patients presenting with moderate or severe VMS was decreased at D90 (P=.005) and at D180 (P=.005). In addition, VMS duration was reduced at D90 (P=.002) and D180 (P < .001). Finally, at D90 and D180, 11.1% and 16.0% of patients, respectively, with initial severe or moderate VMS had a complete response without further symptoms. Among QoL parameters, fatigue decreased significantly. Effectiveness evaluated by doctors was rated as moderate or good to excellent VMS control in 20% and 60% of the patients, respectively. No side effects were recorded in the whole population. This study demonstrated effectiveness and excellent tolerance of Serelys Homme. We observed a significant reduction of the frequency, duration, and intensity of hot flushes and sweats induced by ADT. Serelys Homme increased QoL scores. These encouraging results open the prospect to further studies and Serelys Homme use in patients undergoing ADT for prostate cancer.

MP29-05 TREATMENT PATTERN AND HEALTH-RELATED QUALITY OF LIFE (HRQOL) OF PATIENTS (PTS) WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC) IN THE UNITED STATES (US)

You have accessJournal of UrologyCME1 Apr 2023MP29-05 TREATMENT PATTERN AND HEALTH-RELATED QUALITY OF LIFE (HRQOL) OF PATIENTS (PTS) WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC) IN THE UNITED STATES (US) Neal Shore, Lawrence Karsh, Daniel Shevrin, James Symanowski, Daniel Lin, Jeff Turner, David Russell, Yi Song, James Spalding, Filipa Negreiro, and David Penson Neal ShoreNeal Shore More articles by this author , Lawrence KarshLawrence Karsh More articles by this author , Daniel ShevrinDaniel Shevrin More articles by this author , James SymanowskiJames Symanowski More articles by this author , Daniel LinDaniel Lin More articles by this author , Jeff TurnerJeff Turner More articles by this author , David RussellDavid Russell More articles by this author , Yi SongYi Song More articles by this author , James SpaldingJames Spalding More articles by this author , Filipa NegreiroFilipa Negreiro More articles by this author , and David PensonDavid Penson More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003257.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Therapeutic advances in the management of mCRPC have given clinicians multiple treatment options and the potential for sequencing therapeutic agents, increasing the complexity of treatment decisions. This study aims to describe the treatment patterns and HRQoL of pts with mCRPC in the US from 2015 to 2021. METHODS: This prospective, observational, multicentre study (TRUMPET) enrolled male adult pts who initiated treatment for mCRPC from 147 urology and oncology sites in the US. The data from routine clinic visits and periodic HRQoL questionnaires were collected from Mar 2015 to Apr 2021. The study outcomes assessed patterns of care and HRQoL outcomes (Functional Assessment of Cancer Therapy-Prostate [FACT-P] and Brief Pain Inventory – Short Form [BPI-SF]) associated with mCRPC management. Descriptive analyses were used to evaluate results. RESULTS: Among the enrolled patients, the full analysis set included 832 patients with M1 mCRPC; the safety analysis set included 869 patients with M1 mCRPC. The median duration from initial diagnosis to baseline visit was 4.9 years, median initial prostate-specific antigen (PSA) level at diagnosis was 16.3 ng/mL, and mean (SD) Gleason score was 8.0 (1.18). Novel hormonal therapy (NHT) (enzalutamide and/or abiraterone) and immunotherapy were the most frequent initial treatments (Table). During the follow-up period, 43.8% (n=381) discontinued from the study before the first treatment switch, while 50.1% (n=435) switched treatment, with the majority of pts switching to NHT (n=280, 32.2%). At 1 year follow-up, cumulative first switches were 128 of 158 (81%) from immunotherapy to NHT, 41 of 88 (47%) switched from NHT to a different NHT, 11 of 17 (65%) switched from first-generation anti-androgens (AA) to NHT, 19 of 26 (73%) switched from chemotherapy to NHT, and 6 of 11 (55%) switched from radionuclide therapy to NHT. HRQoL measures showed similar trends (overlapping confidence intervals) of mean change from baseline across different first-line treatment options, irrespective of the initial treatment. CONCLUSIONS: NHT was the preferred first and second-line treatment option in pts with M1 mCRPC. HRQoL was similar regardless of initial treatment. Source of Funding: This study was funded by Astellas Pharma Inc. and Pfizer Inc., the co-developers of enzalutamide. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e382 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Neal Shore More articles by this author Lawrence Karsh More articles by this author Daniel Shevrin More articles by this author James Symanowski More articles by this author Daniel Lin More articles by this author Jeff Turner More articles by this author David Russell More articles by this author Yi Song More articles by this author James Spalding More articles by this author Filipa Negreiro More articles by this author David Penson More articles by this author Expand All Advertisement PDF downloadLoading ...

Exercise interventions for adults with cancer receiving radiation therapy alone.

Exercise interventions for adults with cancer receiving radiation therapy alone.

A prospective study of the relationship between CRPC patient's quality of life after enzalutamide and serum testosterone levels measured via LC‐MS/MS

Enzalutamide (ENZ) is used in the treatment of patients with castration-resistant prostate cancer (CRPC). The quality of life (QoL) of CRPC patients during ENZ treatment is very important, but predictive markers of QoL have not been identified. We investigated the relationship between the serum testosterone (T) level before ENZ treatment and QoL changes in CRPC patients. This prospective study was conducted between 2014 and 2018 at Gunma University Hospital and related facilities. We analyzed 95 patients in whom QoL could be evaluated using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire at baseline, and after 4 and 12 weeks of ENZ treatment. Serum T levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The study population of 95 patients had a median age of 72 years and median prostate-specific antigen level of 21.6 ng/mL. The median overall survival from the commencement of ENZ treatment was 26.8 months. The median serum T level before ENZ treatment was 50.0 pg/mL. The mean total FACT-P scores at baseline, and after 4 and 12 weeks of ENZ treatment, were 95.8, 91.7, and 90.1, respectively. Differences in FACT-P scores between the high T level (High-T) group and low T level (Low-T) group (distinguished based on median split of the T level) were examined. The mean FACT-P scores were significantly higher in the High-T than Low-T group after both 4 and 12 weeks of ENZ treatment (98.5 vs. 84.6 and 96.4 vs. 82.2, respectively, both p < 0.05). The mean FACT-P score was significantly lower in the Low-T group after 12 weeks than before ENZ treatment (p < 0.05). The serum T level before treatment may be useful for predicting QoL changes after ENZ treatment in CRPC patients.

Quality of life outcomes for patients with metastatic castration-resistant prostate cancer and pretreatment prognostic score.

A prognostic risk score (Halabi score) in metastatic castration-resistant prostate cancer (mCRPC) accurately predicts overall survival, but its association with quality of life (QOL) has not been defined. We hypothesize that a higher pretreatment Halabi score is associated with worse QOL outcomes over time in mCRPC patients. Patient-level data from the docetaxel plus prednisone control arm of Mainsail, a Phase 3 clinical trial in mCRPC were accessed via ProjectDataSphere. Pretreatment Halabi score included disease-related factors: metastatic site, opioid use, Eastern Cooperative Oncology Group performance status (ECOG-PS), alkaline phosphatase, albumin, hemoglobin, lactic acid dehydrogenase, and PSA, with higher score indicating worse survival. Three QOL scales were created: Functional Assessment of Cancer Therapy-Prostate (FACT-P, higher score = better QOL), Brief Pain Inventory-Short Form Severity score (BPI-SFSS, higher score = higher pain severity), and BPI-SF Interference score (BPI-SFIS, higher score = greater pain interference). Mixed linear model was used to estimate the associations between Halabi score and QOL scores assessed at different time points (baseline, 2 months, and 6 months). This analysis included 412 mCRPC patients (median age = 68 years, 82% white, 5% Black, median log PSA = 4.4 ng/mL). After multivariable adjustment, Halabi score was significantly associated with QOL scores at all time points. At 6 months, multivariable adjusted FACT-P decreased by 10.0 points (worsening), BPI-SFSS increased by 0.8 points (worsening), and BPI-SFIS increased by 0.9 points (worsening) for each unit increase in Halabi risk score. In multivariable analysis of individual components, ECOG-PS, site of metastasis, and opioid use were significantly associated with worse QOL scores at baseline. Chemotherapy-naïve mCRPC patients with poorer Halabi prognostic risk scores have poorer QOL and greater pain intensity and interference at baseline and during follow-up.

A multi-center, prospective, observational study of patients with prostate cancer being treated with relugolix: OPTYX.

TPS398 Background: Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) receptor agonists or antagonists are the foundation of advanced prostate cancer (aPC) treatment. Relugolix is an oral non-peptide GnRH receptor antagonist approved in the US for the treatment of aPC. In the phase 3 HERO trial, relugolix maintained suppression of testosterone to castration levels in 96.7% of men from Day 29 to 48 weeks, with superiority to leuprolide acetate. Relugolix was well tolerated and associated with a 54% lower risk of major adverse cardiovascular events relative to leuprolide acetate (Shore N, NEJM 2020;382;23). The goal of this current study (OPTYX) is to generate real-world evidence about the safety and effectiveness of relugolix in patients with prostate cancer during routine clinical care. Methods: This prospective observational cohort study (registry) is enrolling patients who have planned initiation with relugolix within 1 month prior to the time of study enrollment. The study is designed to prospectively understand the actual experience of patients with prostate cancer treated with relugolix through data collection on patients selected for treatment, treatment patterns, adherence, patient reported quality of life (QoL) and safety data. Additionally, a better understanding of the trajectory of patients with prostate cancer following cessation of relugolix therapy will be gained by observing the clinical course of the disease, health outcomes, and health-related quality-of-life (HRQoL) in these patients. Inclusion criteria include patients &gt; 18 years old with prostate cancer and planned total treatment with relugolix of at least 4 months. Estimated enrollment is 1000 patients, and patients will be followed for up to 5 years. In addition to assessing routine clinical care and disease progression, patient reported outcomes will be assessed with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) for HRQoL and Simplified Medication Adherence Questionnaire (SMAQ) for adherence at 3 and 6 months then every 6 months. Clinical trial information: NCT05467176 .

Effect of cerebral dopamine metabolism genetic polymorphism on patient-reported quality-of-life (QOL): An analysis of the E3805 CHAARTED trial.

123 Background: QOL outcomes have been associated with specific genetic variants in neurotransmitter metabolism. One such variant associated with reduced symptoms in placebo studies is in the rs4680 SNP of Carboxy-O-Methyltransferase (COMT). This variant is associated with reduced COMT enzymatic activity, higher cerebral dopamine levels, and improved mood. The interaction between this germline variant and cancer-directed treatment on QOL is undefined. A priori, we hypothesized that the COMT rs4680 SNP would be associated with better pain and QOL patient reported outcomes (PROs), than wildtype (WT) COMT within the E3805 CHAARTED Trial. Methods: E3805 compared docetaxel + androgen deprivation therapy (ADT+D) vs ADT in patients with metastatic hormone sensitive prostate cancer (mHSPC). PROs were collected at baseline, 3, 6, 9, and 12 months. Blood samples were genotyped prior to treatment. We compared PROs between patients with COMT WT vs rs4680 SNP within treatment arms longitudinally. PROs include Brief Pain Inventory (BPI) classified as: no (0), minimal (1), or more (≥2) pain, and BPI interference (range 0-10, 0= no pain or interference), and the Functional Assessment of Cancer Therapy-Prostate (FACT-P, higher score= better QOL, clinically important difference (CID)= 6). Descriptive statistics were used to characterize QOL over time. Fisher’s exact test, Wilcoxon rank sum test and mixed effects models were used to evaluate the associations between SNP and QOL in each arm. Results: Of 790 participants, 550 with SNP data were included. In the ADT+D arm, SNPs were not associated with PROs at any time point. In contrast, in the ADT alone arm, when compared to WT, rs4680 was associated with less pain at 3 months, less interference at 3, 6 and 9 months, and better QOL at 6 months (met criteria for CID). Conclusions: The rs4680 SNP, often associated with higher cerebral dopamine levels and improved QOL, was associated with less pain and superior QOL among patients with mHSPC treated with ADT, but not chemohormonal therapy. This is the first hypothesis driven genotyping study to demonstrate that genetics are associated with QOL in patients with cancer, especially when treatment does not cause profound symptoms. Clinical trial information: NCT00309985 . [Table: see text]

Alliance A031902 (CASPAR): A randomized phase (ph) 3 trial of enzalutamide with rucaparib/placebo in first-line metastatic castration-resistant prostate cancer (mCRPC).

TPS277 Background: Despite a growing number of treatment options for first-line mCRPC, approximately 40% of patients (pts) have radiographic progression within the first year. Co-inhibition of androgen receptor (AR) and PARP is a promising therapeutic strategy that leverages synthetic lethality induced by impaired double-strand DNA repair. Two phase III studies have shown improvement in radiographic progression-free survival (rPFS) in HRR-mutant pts with abiraterone + PARPi combinations vs abiraterone alone. However, the results in HRR-wild type pts are conflicting, with only one of the studies demonstrating a benefit with the abiraterone + PARPi combination. ENZ + RUCA has shown an acceptable safety profile &amp; no significant drug-drug interactions (S-DDI) in a phase 1b trial. This allows its evaluation in mCRPC. Methods: CASPAR (A031902) is a phase 3 study in which 984 pts will be randomized on a 1:1 basis to ENZ plus RUCA/PBO. HRR gene aberration is not required for enrollment. All pts will undergo next-generation targeted exome sequencing from archival tumor tissue (new biopsy only required if no archival tissue is available). Treatment will be continued until disease progression and crossover is not allowed. Key eligibility criteria are age ≥ 18 years, ECOG PS 0-2, biopsy-proven prostate adenocarcinoma, progressive (PSA or radiographic) disease per Prostate Cancer Working Group 3 guidelines, measurable or non-measurable disease per RECIST 1.1, no prior treatment for mCRPC (prior docetaxel, abiraterone, darolutamide, or apalutamide in non-mCRPC setting is allowed), no significant uncontrolled comorbidity, and no medications with S-DDI with ENZ/RUCA. Hierarchical co-primary endpoints are overall survival (OS) and rPFS. The OS analysis will be undertaken as a primary endpoint if the rPFS endpoint is met. For a one-sided logrank test with a type 1 error rate equal to 0.025, the study has 90% power to detect a hazard ratio (HR) of 0.71 in rPFS (median rPFS of 15 and 21 months in control and combination arms, respectively), and 80% power to detect an HR of 0.80 in OS (median OS of 32 and 40 months, respectively). Key secondary endpoints are rPFS and OS in pts with vs without pathogenic BRCA1, BRCA2, or PALB2 alterations; and differences in adverse events and quality of life (QOL) outcomes between the treatment arms. QOL assessments include Functional Assessment of Cancer Therapy–Prostate (FACT-P), Brief Pain Inventory Short Form (BPI-SF), and EQ-5D-5L. A key correlative endpoint is the sensitivity of ctDNA testing for HRR gene alterations. Enrollment began in July 2021 &amp; the study is available for participation to all US-NCTN sites. Clinical trial information: NCT04455750 .

Estetrol Prevents Hot Flushes and Improves Quality of Life in Patients with Advanced Prostate Cancer Treated with Androgen Deprivation Therapy: The PCombi Study

BackgroundAndrogen deprivation therapy (ADT) for prostate cancer (PCa) is accompanied by side effects affecting health-related quality of life (HRQL). ObjectiveTo assess the effects of the fetal estrogen estetrol (E4) on symptoms related to estrogen and androgen deficiency, and on HRQL measured using the validated Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. Design, setting, and participantsThis was a phase 2, double-blind, randomized, placebo-controlled study in patients with advanced PCa. InterventionPatients receiving ADT were randomly assigned at a 2:1 ratio to daily treatment with a high dose of E4 (HDE4; n = 41) or placebo (n = 21) for 24 wk. Outcome measurements and statistical analysisThe primary outcome was the effect of HDE4 cotreatment on hot flushes (HFs). Secondary outcomes were the Q-Man questionnaire for evaluation of the effect on estrogen and androgen deficiency symptoms, and the FACT-P questionnaire for evaluating HRQL. Results and limitationsAt 24 wk, the number of patients experiencing HFs was significantly lower in the HDE4 group than in the placebo group (14.3% vs 60.0%; p < 0.001). HDE4 treatment was associated with lower incidence of night sweats, arthralgia, and fatigue, but more nipple tenderness and gynecomastia. At 24 wk, the mean HRQL score favored HDE4 over placebo for the FACT-P total score (122.2 ± 12.3 vs 118.7 ± 19.7) and for several other FACT subscales. ConclusionsDaily HDE4 coadministration almost completely prevented HFs in patients with advanced PCa treated with ADT. HDE4 also had positive effects on HRQL and counteracted other estrogen deficiency symptoms caused by ADT. These data support the dual efficacy concept of ADT and HDE4 to improve HRQL and increase the antitumor effect of ADT. Patient summaryFor patients on androgen deprivation therapy for advanced prostate cancer, cotreatment with a high dose of estetrol almost completely prevents the occurrence of hot flushes and improves quality of life and well-being, but nipple sensitivity and an increase in breast size may occur.

Randomized, Open-Label Phase 2 Study of Apalutamide plus Androgen Deprivation Therapy versus Apalutamide Monotherapy versus Androgen Deprivation Monotherapy in Patients with Biochemically Recurrent Prostate Cancer.

Purpose This randomized phase 2 study sought to assess the treatment effect of a finite duration of apalutamide with and without androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BCR PC). Materials and Methods. Patients with BCR PC after primary definitive therapy and prostate-specific antigen (PSA) doubling time ≤12 months were randomized to open-label apalutamide (240 mg/d) alone, apalutamide plus ADT, or ADT alone (1 : 1:1 ratio) for 12 months followed by a 12-month observation period (NCT01790126). Mean changes from baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) at 12 months (primary endpoint) and other prespecified assessments of health-related quality of life (HRQoL), PSA nadir, time to PSA progression, time to testosterone recovery, recovered testosterone >150 ng/dL without PSA progression at 24 months, and molecular markers were evaluated. Results In 90 enrolled patients (apalutamide plus ADT (n = 31), apalutamide (n = 29), ADT (n = 30)), FACT-P at 12 months was not significantly different between apalutamide, ADT and apalutamide, and ADT groups. Addition of apalutamide to ADT prolonged time to PSA progression but this change did not reach statistical significance (hazard ratio (HR): 0.56, 95% confidence interval (CI): 0.23–1.36, P=0.196); time to testosterone recovery was similar in the ADT-containing groups. In apalutamide plus ADT, apalutamide, and ADT groups, 37.9%, 37.0%, and 19.2% of patients, respectively, had testosterone >150 ng/dL at 24 months without confirmed PSA progression. Of the few biomarkers expressed in blood, EPHA3 was significantly associated with shorter time to PSA progression (P=0.02) in the overall population. Conclusions HRQoL was similar in patients treated with apalutamide alone, ADT alone, or their combination, although apalutamide plus ADT did not demonstrate statistically significant noninferiority in change from baseline in overall HRQoL. The aggregated efficacy and safety outcomes support further evaluation of apalutamide plus ADT in BCR PC.

2-weekly versus 3-weekly docetaxel for metastatic castration-resistant prostate cancer: complete quality of life results from the randomised, phase-III PROSTY trial

Introduction Treatment with 2-weekly docetaxel 50 mg/m2 was shown to improve overall survival and was better tolerated than the standard 75 mg/m2 3-weekly regimen in men with metastatic castration-resistant prostate cancer (mCRPC) in the original randomised PROSTY trial. The aim of this study was to investigate, whether quality of life (QoL) effects would differ between the 2-weekly docetaxel 50 mg/m2 regimen from the standard 3-weekly 75 mg/m2 treatment. Materials and Methods QoL data were collected with the Functional Assessment of Cancer Therapy – Prostate (FACT-P) and Functional Assessment of Cancer Therapy Advanced Prostate Symptom Index − 8 Item version (FAPSI-8). Pain was measured using the Visual Analogue Scale (VAS). A total of 743 forms from 163 patients were analysed in Arm A (2-weekly docetaxel), and 704 forms from 173 patients were analysed in Arm B (3-weekly docetaxel). The data were analysed using both the Wilcoxon signed rank test (with Holm–Bonferroni adjustment) and Mann–Whitney U models. Results No major differences were found in total QoL. Total QoL was higher at month 8 in Arm B (p = .020), but this was reversed in the following month (p = .043), and no statistically significant differences were found during other months. Compared to Arm A, participants in Arm B had longer-lasting deterioration in FAPSI-8 scores and emotional well-being subdomain at the beginning of treatment (p < .05). Various one-month differences were found in FACT-P subdomains (except for functional well-being), and these favoured participants in Arm A, except for the prostate-cancer subdomain. There were no differences in pain. Conclusion Based on our results, 2-weekly docetaxel was not inferior to 3-weekly docetaxel in terms of total health-related QoL and seemed to be superior at least in terms of the FAPSI-8 and emotional well-being subdomain in the first three to four months of treatment. More research on the topic is suggested to confirm the results.

Health-related quality of life (HRQoL) and pain in the MAGNITUDE study of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations.

5060 Background: Results from the international, randomized, double-blind, phase 3 MAGNITUDE study demonstrated that NIRA + AAP improved radiographic progression-free survival, time to cytotoxic chemotherapy, and time to symptomatic progression, with manageable toxicity in pts with mCRPC and HRR alterations (9-gene panel). Here, we report HRQoL and pain in MAGNITUDE. Methods: Eligible pts with mCRPC and HRR alterations were randomized 1:1 to NIRA + AAP or placebo (PBO) + AAP orally daily in 28-day cycles. Pts had ECOG status ≤1 and a Brief Pain Inventory–Short Form (BPI-SF) worst pain score ≤3 in prescreening. HRQoL assessments on day 1 of specified cycles included Functional Assessment of Cancer Therapy–Prostate (FACT-P) and BPI-SF. Changes from baseline were compared between treatment arms using repeated measures analysis. Proportional hazards regression models were used to compare time to deterioration (TTD) in worst pain intensity between arms. Results: Compliance for FACT-P and BPI-SF was &gt; 80%. Most pts maintained low pain levels over time. Repeated measures analyses showed no clinically meaningful differences in pain over time or between arms. Median TTD in pain intensity was not reached in either arm. At the 25th percentile, there was a trend toward longer TTD in pain intensity with NIRA + AAP vs PBO + AAP (11.1 vs 10.1 mo; HR, 0.87; 95% CI, 0.61-1.24). HRQoL was maintained with NIRA + AAP, with no clinically meaningful differences in FACT-P total score over time or between arms. There was a trend toward greater worsening in early cycles on FACT-P physical wellbeing with NIRA + AAP vs PBO + AAP, driven by events within the known safety profile of NIRA + AAP (worsening of side effect bother, lack of energy, and nausea); however, overall, most pts reported minimal side effect burden (Table). Conclusions: In MAGNITUDE, most pts maintained low pain levels and positive HRQoL over time, with no clinically meaningful differences between treatment arms, further supporting the use of NIRA + AAP in pts with mCRPC and HRR alterations. Side effect burden was perceived as low in both arms. Although more pts on NIRA+AAP reported worsening side effects, the symptoms were generally perceived as mild. Clinical trial information: NCT03748641. [Table: see text]

Alliance A031902 (CASPAR): A randomized, phase (ph) 3 trial of enzalutamide with rucaparib/placebo in first-line metastatic castration-resistant prostate cancer (mCRPC).

TPS5107 Background: Despite a growing number of treatment options for first line mCRPC, approximately 40% of patients (pts) have radiographic progression within the first year. Androgen receptor (AR) signaling inhibition increases genomic instability with double-strand DNA breaks &amp; co-inhibition of AR &amp; PARP induces synthetic lethality in multiple preclinical models. Homologous recombination repair (HRR) gene aberrations do not appear to be necessary for this synergy as demonstrated in a ph 3 clinical trial of abiraterone &amp; olaparib where this combination improved radiographic progression-free survival (rPFS) in HRR-wild-type pts compared with abiraterone alone. A ph 1b trial has since shown that enzalutamide plus rucaparib has acceptable safety profile &amp; no significant drug-drug interactions (S-DDI). Methods: CASPAR/A031902 (NCT04455750) is a ph 3 study in which 984 pts will be randomized 1:1 to enzalutamide plus rucaparib or placebo. HRR gene aberration is not required for enrollment. All pts will undergo next-generation targeted-exome sequencing from archival tumor tissue (new biopsy only required if no archival tissue available). Treatment will be continued until disease progression &amp; crossover is not allowed. Key eligibility criteria are age ≥ 18 years, ECOG PS 0-2, biopsy-proven prostate adenocarcinoma, progressive (PSA or radiographic) disease per Prostate Cancer Working Group 3 guidelines, measurable or nonmeasurable disease per RECIST 1.1, no prior treatment for mCRPC (prior docetaxel, abiraterone, darolutamide, or apalutamide in non-mCRPC setting is allowed), no significant uncontrolled comorbidity, &amp; no medications with S-DDI with enzalutamide/rucaparib. Hierarchical co-primary endpoints are rPFS &amp; overall survival (OS). The OS analysis will be undertaken as a primary endpoint if the rPFS endpoint is met. For a one-sided logrank test with a type 1 error rate equal to 0.025, the study has 90% power to detect a hazard ratio (HR) of 0.71 in rPFS (median rPFS of 15 &amp; 21 months in control &amp; combination arms, respectively) &amp; 80% power to detect an HR of 0.80 in OS (median OS of 32 &amp; 40 months, respectively). Key secondary endpoints are rPFS &amp; OS in pts with vs without pathogenic BRCA1, BRCA2, or PALB2 alterations; &amp; differences in adverse events &amp; quality of life (QOL) outcomes between the treatment arms. QOL assessments include Functional Assessment of Cancer Therapy–Prostate (FACT-P), Brief Pain Inventory Short Form (BPI-SF) &amp; EQ-5D-5L. A key correlative endpoint is the sensitivity of ctDNA-based testing for alterations in HRR genes. Enrollment to CASPAR began in July 2021 &amp; the study is available for participation to all US-NCTN sites with a projected enrollment of 3 years. Support: U10CA180821, U10CA180882, U24CA196171; U10CA180888. Clinical trial information: NCT04455750.

Pilot trial of physical and cognitive changes related to fall risk in enzalutamide patients with castration-resistant prostate cancer (CRPC).

e17018 Background: Advanced prostate cancer disproportionally affects older men (age ≥ 75 years). Despite representing only 26% of diagnoses, older men represent half of those diagnosed with metastatic disease and half of all prostate cancer deaths. Treatment options for CRPC include enzalutamide (enza), a competitive inhibitor of the androgen receptor, which shows improved overall survival and other cancer-specific responses in older men. However, enza is also reportedly associated with increased fall frequency of unclear pathophysiology. This pilot study examines strength, balance, and cognition in men before and 12 weeks after starting enza therapy for CRPC. Methods: This prospective single-arm study included men about to begin enza for CRPC, ≥ 65 years, able to ambulate independently. The following tests were administered at baseline and 12 weeks after initiation of enza: Sit-to-stand test (STS), Timed-Up-and-Go test, proprioception assessment, computerized dynamic posturography including sensory organization test (SOT), motor control test (MCT), and limits of stability; Functional Assessment of Cancer Therapy-Prostate, BPI-SF, Activities-specific Balance Confidence (ABC), Montreal Cognitive Assessment (MoCA), International Physical Activity Questionnaire (IPAQ), and the Godin leisure-time exercise questionnaire (GLTEQ). Falls were assessed with self-report fall diaries and calls from study team to participants over the course of 12 months. Results: Twenty-five participants enrolled. Median age was 75 years. There were 23 (92%) with both baseline and 12-week assessments, and 21 (84%) participants had complete falls data. From baseline to the 12-week follow up, ABC scale scores decreased (median 90.4 to 85.2), GLTEQ scale scores decreased (median 31.4 to 28.0), and time sitting per day from IPAQ increased (4 hours to 5 hours). Of those evaluable for falls, 15 (71%) did not fall during the 12 months and 6 (29%) fell at least once. The fallers and non-fallers did not differ with respect to age or MoCA scores at baseline and on re-assessment. Those who fell performed more poorly on the STS test, the ABC and the dynamic posturography evaluations. Those who fell also had a higher level of activity by GLTEQ. Conclusions: This pilot study does not clearly elucidate the pathophysiology of falls in older men with CRPC taking enza but does provide useful and important guidance for the design of future studies in this area. Baseline and 12-week testing should be repeated at the 24-week time-point to allow for sufficient exposure to enza. To avoid confounding by practice effects, physical tests, particularly dynamic posturography, should be performed at least once prior to baseline assessment. Further research is needed to understand the mechanisms underlying the increased risk of falls previously observed in older men with CPRC taking enza.