Treatment patterns and outcomes in patients with nonmetastatic castration-resistant prostate cancer in the United States.

Aim: Androgen receptor pathway inhibitors (ARPIs) prolong metastasis-free survival and overall survival in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). This study aimed to evaluate real-world treatment patterns, utilization and survival outcomes in patients with nmCRPC.Patients & methods: This retrospective cohort study used Optum database electronic health records of patients with nmCRPC from 1 January 2007 to 31 December 2020 in the US.Results: Of 1955 patients, >80% received androgen-deprivation therapy (ADT) alone or ADT + first-generation nonsteroidal antiandrogen (NSAA) as first-line treatment, while only 8.24% received ADT + ARPI. ADT + ARPI remained underutilized even among those with high-risk nmCRPC. Further, ADT + NSAA had no survival benefit compared with ADT alone.Conclusion: Practice-improvement strategies are needed for treatment intensification with ARPIs for patients with nmCRPC.

Prostate cancer cells often use hormones called androgens to grow and survive. Hormone therapy is a treatment that lowers the amount of these hormones in the body to slow down the cancer's growth. It includes androgen-deprivation therapy (ADT), which can either be used alone or along with nonsteroidal antiandrogens (NSAAs) or with androgen receptor pathway inhibitors (ARPIs). Nonmetastatic castration-resistant prostate cancer (nmCRPC) is defined as prostate cancer that has not spread to other parts of the body but exhibits rising levels of serum prostate-specific antigen despite surgery or ADT to reduce androgens. Research shows that ARPIs can improve survival in patients with nmCRPC, but more data on its use are needed. This study looked at the electronic health records of patients with nmCRPC to review the treatment they had received and their survival. Between 2008 and 2020, most patients received ADT alone or with NSAA. Even though the number of patients receiving ADT with ARPI increased during this period, it remained underused, even in patients with a high risk of cancer spreading to other body parts. Post-2018, even after 2 years of these drugs being available, only about one in five patients received ADT with ARPI. Also, people who received ADT with NSAA did not have a longer survival than patients treated with ADT alone. The study indicates that ARPIs, which could improve survival of patients with nmCRPC, are not being utilized optimally. Strategies that promote early use of ARPIs are needed to improve survival of patients with nmCRPC.

The Role of Physician Specialty in the Underutilization of Standard-of-Care Treatment Intensification in Patients With Metastatic Castration-sensitive Prostate Cancer.

PURPOSE: We evaluate utilization of treatment intensification of androgen deprivation therapy with androgen receptor pathway inhibitor/docetaxel for metastatic castration-sensitive prostate cancer patients across physician specialties. MATERIALS AND METHODS: This retrospective study identified patients with metastatic castration-sensitive prostate cancer in the Optum Research Database between 2014 and 2019. Adult men with ≥1 claim for metastatic disease within 90 days before or any time after the first prostate cancer claim who received androgen deprivation therapy were included. Physician specialty, determined from medical/pharmacy claims during each line of therapy, was categorized as urologist only, oncologist only, both (urologists and oncologists), or other (other specialties). Treatment intensification and patient characteristics were analyzed descriptively. RESULTS: Of 4,675 patients, 16% were treated by urologists only, 20% by oncologists only, 63% by both, and 1.1% by others. The most frequent first line of therapy was androgen deprivation therapy ± first-generation nonsteroidal antiandrogens (>50%). Androgen deprivation therapy + docetaxel use declined over time, while androgen deprivation therapy + androgen receptor pathway inhibitor use increased. Patients seen by oncologists or both were younger, had fewer comorbidities, and were likelier to receive treatment intensification compared to those treated by urologists. By 2019, however, treatment intensification remained <40% from oncologists only or both, and <15% from urologists only. In the second and third lines of therapy, androgen deprivation therapy + androgen receptor pathway inhibitor was the most prescribed regimen across specialties (>50%). CONCLUSIONS: Treatment intensification was underused in first lines of therapy across urology and oncology specialties despite evidence of improved survival. In subsequent lines, androgen deprivation therapy + androgen receptor pathway inhibitor was prescribed more frequently across specialties. These results underscore the need for earlier treatment intensification by urologists and oncologists.

Patient Preferences for Attributes of Androgen Deprivation Therapies in Prostate Cancer: A Discrete Choice Experiment with Latent Class Analysis.

INTRODUCTION: Medical androgen deprivation therapy (ADT) options have expanded for patients with advanced prostate cancer (PC). Historically, ADT was primarily available in long-acting injectable formulations. In 2020, the first oral formulation was US Food and Drug Administration-approved for adults with advanced PC. This study's aim was to assess patient preferences for attributes of medical ADT, including mode of administration, side effects, impact on sexual interest, and out-of-pocket (OOP) costs, and to segment respondents into distinct groups based on their treatment choice patterns. METHODS: A cross-sectional survey was conducted among US residents aged > 40 years with PC, employing a discrete choice experiment to assess preferences for ADT attributes. For each choice task, respondents were asked to select the hypothetical treatment profile that they preferred out of two presented. Latent class analysis (LCA) was conducted to estimate attribute-level preference weights and calculate attribute relative importance for groups of respondents with similar treatment preferences. RESULTS: A total of 304 respondents completed the survey (mean age 64.4 years). LCA identified four preference groups, named according to the attribute each group considered most important: Sexual interest, Cost-sensitive, Favors daily pill, and Favors injection. Most respondents in the Sexual interest group were < 65 years, while the Cost-sensitive group was mostly ≥ 65 years. Favors daily pill had the highest proportion of ADT-naïve individuals. On average, respondents in these groups preferred an oral medication. Favors injection, which had the highest proportion of ADT-experienced individuals, preferred infrequent intramuscular injections, lower chance of post-ADT testosterone recovery, and lower OOP cost. CONCLUSION: Respondents differed in their preferences regarding ADT attributes, highlighting the need for patient involvement in their treatment decisions. Effective communication between healthcare providers and patients about the benefits and risks of available therapies should be encouraged to ensure that patients receive the PC treatment that best meets their needs.

Prostate cancers often depend on the male sex hormone, testosterone, to grow. Androgen deprivation therapy (ADT) is used to lower testosterone levels in patients with advanced prostate cancer. ADT options available to patients have different characteristics, including how they are taken (injection or pill), side effects, impact on sexual interest, and costs. Researchers wanted to understand which ADT characteristics were most important to groups of patients with similar preferences. To do this, they gave 304 patients a series of two hypothetical (meaning not real) examples of ADT options with different characteristics and asked them to choose the option that they preferred most. Researchers found that patients could be separated into four different groups based on their preferences for ADT characteristics. One group preferred an ADT that had the least impact on their interest in sex. These patients were mainly younger than 65 years old. A second group preferred a lower cost ADT. These patients were mainly 65 years or older. A third group preferred a pill that could be taken once a day by mouth. Most of these patients did not take ADT in the past. A fourth group preferred an ADT that was given in a physician's office as an injection every 6 months. These patients mainly had taken ADT in the past. This study shows that patients have different preferences for ADT treatment characteristics. It is important for doctors to discuss the different ADT options with patients to find the treatment that best meets their needs.

Fatigue Management in Advanced Prostate Cancer: Real-World Insights From Qualitative Interviews With Patients.

BACKGROUND: Patients with advanced prostate cancer (PC) commonly experience fatigue related to the disease itself and its treatment, which affects their quality of life. There are limited real-world data available on patients' experiences of fatigue while receiving PC treatment and its management. PATIENTS AND METHODS: This was a cross-sectional, noninterventional qualitative study involving individual concept-elicitation interviews with patients in the United States. Patients with advanced PC aged ≥18 years who had experienced fatigue and were on androgen-deprivation therapy in combination with second-generation androgen receptor pathway inhibitors were interviewed and their experiences quantified. RESULTS: Of the 143 patients screened, 13 qualified and 11 completed the interview. Most patients used the term "fatigue" (n = 8) to describe their experiences of tiredness, exhaustion, lack of energy, and weakness. Most patients (n = 8) did not receive any form of educational support from their healthcare providers (HCPs), but some expressed an interest in receiving this support (pamphlets, n = 4; discussion with HCPs, n = 4; online resources, n = 3). Most patients (n = 9) self-discovered fatigue-management strategies over the course of their disease and treatment. Patients found that rigorous exercise (n = 5), regular naps (n = 2), increased rest (n = 3), and a healthy diet (n = 3) were the most effective approaches for managing their fatigue. CONCLUSION: Tools are needed to support HCPs with counseling patients with PC for effective management of disease- and treatment-related fatigue.

Real-world overall survival with abiraterone acetate versus enzalutamide in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer.

BACKGROUND: There are no large head-to-head phase 3 clinical trials comparing overall survival (OS) for abiraterone and enzalutamide. This study used Medicare claims data to compare OS in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) who initiated abiraterone or enzalutamide. METHODS: This retrospective analysis of the Medicare database (2009-2020) included adult men with ≥1 claim for prostate cancer, metastatic diagnosis, and no prior chemotherapy or novel hormone therapy who initiated first-line (1L) abiraterone or enzalutamide in the index period (September 10, 2014 to May 31, 2017). Cox proportional-hazards models with inverse probability treatment-weighting (IPTW) were used to compare OS between abiraterone- and enzalutamide-treated patients, adjusting for baseline characteristics. Subgroup analyses by baseline characteristics were also conducted. RESULTS: Overall, 5506 patients who received 1L abiraterone (n = 2911) or enzalutamide (n = 2595) were included. Median follow-up was comparable in both cohorts (abiraterone, 19.1 months; enzalutamide, 20.3 months). IPTW-adjusted median OS (95% CI) was 20.6 months (19.7‒21.4) for abiraterone and 22.5 months (21.2‒23.8) for enzalutamide, with an IPTW-adjusted hazard ratio (95% CI) of 1.10 (1.04-1.16). Median OS was significantly shorter for abiraterone versus enzalutamide in patients ≥75 years old; White patients; patients with baseline diabetes, cardiovascular disease, both diabetes and cardiovascular disease, and renal disease; and across all socioeconomic strata. CONCLUSIONS: In the Medicare chemotherapy-naïve mCRPC population, 1L abiraterone was associated with worse OS versus enzalutamide in the overall population and among subgroups with older age and comorbidities, supporting findings from previous real-world studies and demonstrating a disparity in outcomes.

Real-world outcomes following biochemical recurrence after definitive therapy with a short prostate-specific antigen doubling time: potential role of early secondary treatment.

BACKGROUND: The natural history of biochemical recurrence (BCR) managed with delayed hormonal therapy is well documented by data from Johns Hopkins. However, as many patients receive treatment prior to metastasis, we evaluated the natural history and role of prostate-specific antigen doubling time (PSADT) in a more contemporary cohort of BCR patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC). METHODS: Patients in the Veterans Health Administration (VHA; 01/01/06 to 06/22/20) with nmCSPC and BCR were divided into rapid ( ≤9 months) and less rapid ( >9 to ≤15 months) PSADT cohorts. Patients with PSADT >15 months were excluded as outcomes, even with delayed treatment, are excellent. Outcomes included time to first antineoplastic therapy after BCR, metastasis, metastasis-free survival (MFS), and overall survival (OS). Cox models adjusted for baseline demographics and clinical characteristics. RESULTS: Overall, 781 patients with BCR were identified (502 rapid; 279 less rapid PSADT). Rapid PSADT was associated with shorter time to first systemic antineoplastic therapy (median 11.4 vs. 28.3 months, adjusted hazard ratio [95% confidence interval] 2.17 [1.83-2.57]), metastasis (102.4 months vs. not reached, 1.79 [1.33-2.40]), MFS (76.1 vs. 106.3 months, 1.73 [1.33-2.24]), and OS (120.5 vs. 140.5 months, 1.76 [1.22-2.54]) versus less rapid PSADT. CONCLUSION: Most patients with rapid PSADT underwent secondary treatment within 1 year after BCR. More contemporary patients treated with early secondary treatment had better outcomes than historical data from patients who had delayed treatment. Whether these results reflect the benefits of early secondary treatment or overall improvements in prostate cancer outcomes over time requires further study.

Risk of cardiovascular events following intermittent and continuous androgen deprivation therapy in patients with nonmetastatic prostate cancer.

BACKGROUND: Intermittent androgen deprivation therapy (iADT) alleviates some side effects of continuous (c) ADT in patients with prostate cancer (PC), but its relative impact on ADT-associated comorbidities is uncertain. We assessed real-world use of iADT and cADT and associated risk of cardiovascular and endocrine/metabolic events in patients with nonmetastatic (nm) PC. METHODS: This retrospective longitudinal cohort study included patients with nmPC initiating systemic ADT with gonadotropin-releasing hormone agonists (goserelin, histrelin, leuprolide, and triptorelin) or antagonists (degarelix) in the US Surveillance, Epidemiology and End Results-Medicare database (2010-2017), who had ≥ 36 months of continuous insurance coverage, unless death occurred, and did not receive chemotherapy or next-generation hormonal therapies during follow-up (through 2019). Risk of major adverse cardiovascular events (MACE [myocardial infarction, stroke, cardiomyopathy/heart failure, pulmonary embolism, ischemic heart disease, all-cause mortality]) and endocrine/metabolic events (diabetes, hypercholesterolemia, bone fractures, and osteoporosis) were examined between cohorts. Inverse probability of treatment-weighted Cox regression models estimated adjusted hazard ratios (HRs) of the outcomes. RESULTS: Of 10,655 eligible patients, 2,095 (19.7%) received iADT and 8,560 (80.3%) cADT. Median follow-up was 43.9 and 48.4 months and median ADT duration (excluding iADT gaps) was 22.0 and 13.5 months for the iADT and cADT cohorts, respectively. Patients receiving cADT had a lower risk of MACE vs. iADT (HR 0.90; 95% confidence interval [CI] 0.83-0.96). No difference in risk of endocrine/metabolic events was observed (HR 0.97; 95% CI 0.92-1.03). Subgroup analysis found that the difference in MACE was maintained in patients with a history of cardiovascular disease (HR 0.90; 95% CI 0.83-0.98) and eliminated in patients without (HR 0.94; 95% CI 0.82-1.08). CONCLUSIONS: Patients with nmPC who received cADT had a lower risk of MACE and similar risk of endocrine/metabolic events vs. those who received iADT. Further research assessing both regimens is needed to inform treatment decisions.

Assessing racial differences in time to subsequent treatment following androgen deprivation therapy among Veterans with prostate cancer.

Background For metastatic and certain advanced prostate cancer (PC), guidelines support intensified androgen deprivation therapy (ADT) as first-line (1L) systemic treatment for improved outcomes. However, some patients receive ADT alone, leading to tumor progression requiring 2nd line therapy. Despite significant racial disparities in PC outcomes, there are no population-level studies assessing racial differences in time to subsequent treatment after 1L ADT. Methods We performed a retrospective population-level analysis to assess the association between race and time to subsequent treatment after ADT in the Veterans Affairs Health Care System. Primary outcome was time from ADT monotherapy to subsequent treatment, defined as receipt of androgen receptor pathway inhibitor (ARPI), non-steroidal first-generation anti-androgen (NSAA), chemotherapy, or other treatments. We used Cox models and Kaplan-Meier (KM) analyses to estimate subsequent treatment rates by Non-Hispanic White [NHW], Non-Hispanic Black [NHB], Hispanic and Other patients adjusted for baseline covariates. Results From 2001-2021, 141,495 PC patients received ADT alone. During median (IQR) follow-up of 51.1 (22.8, 97.2) months, 28,144 patients (20%) had subsequent treatment: 11,319 (40%) ARPIs, 12,990 (46%) NSAAs, 3,402 (12%) chemotherapy and 433 (2%) other 2nd line therapies. NHB had significantly lower subsequent treatment rates (HR = 0.82, 95%CI = 0.80-0.85) compared to NHW. Both Hispanic (HR = 0.93, 95%CI = 0.88-0.98) and Other men (HR = 0.91, 95%CI = 0.84-0.98), also had lower subsequent treatment rates. Conclusions All races examined had significantly lower rates of subsequent treatment after 1L ADT relative to NHW. Further investigation is needed to determine if these lower rates of subsequent treatment reflect lower rate of progression or undertreatment of progressing patients.

Implications of Delayed Testosterone Recovery in Patients with Prostate Cancer.

To assess the clinical impact of delayed testosterone recovery (TR) following the discontinuation of medical androgen deprivation therapy (ADT), a retrospective, longitudinal analysis was conducted in adult males with prostate cancer using the Optum® de-identified Electronic Health Record data set and Optum® Enriched Oncology Data (2010-2021). Of 3875 patients who initiated and discontinued ADT, 1553 received one or more testosterone-level tests within the 12 mo following discontinuation and were included in this study. These 1553 patients were categorized into two cohorts: 25% as TR (testosterone levels >280 ng/dl at any test within 12 mo following ADT discontinuation) and 75% as non-TR. At baseline, non-TR patients were older, had lower testosterone levels, and were more likely to have diabetes, hyperlipidemia, and hypertension, but less likely to have sexual dysfunction. After adjustment for baseline characteristics, the TR cohort had a lower risk of new-onset diabetes (hazard ratio [HR] 0.47; 95% confidence interval [CI] 0.27-0.79), trended toward a lower risk of new-onset depression (HR 0.58; 95% CI 0.33-1.02), and had a higher likelihood of seeking treatment for sexual dysfunction (HR 1.33; 95% CI 0.99-1.78) versus the non-TR cohort. These findings support monitoring testosterone levels after ADT discontinuation to manage potential long-term comorbidities in patients with prostate cancer. Patient summary: This real-world analysis of males with prostate cancer who were treated with medical androgen deprivation therapy (ADT) found that most patients did not have their testosterone level checked in the 12 mo after stopping ADT. Of those who did, 75% did not achieve normal testosterone levels (>280 ng/dl), and these patients were more likely to experience new-onset diabetes than those who achieved normal testosterone levels. These results suggest that to ensure effective clinical decision-making, physicians should check patients' testosterone levels after stopping ADT.

Emerging racial disparities among Medicare beneficiaries and Veterans with metastatic castration-sensitive prostate cancer.

BACKGROUND: Previous studies have shown that Black men receive worse prostate cancer care than White men. This has not been explored in metastatic castration-sensitive prostate cancer (mCSPC) in the current treatment era. METHODS: We evaluated treatment intensification (TI) and overall survival (OS) in Medicare (2015-2018) and Veterans Health Administration (VHA; 2015-2019) patients with mCSPC, classifying first-line mCSPC treatment as androgen deprivation therapy (ADT) + novel hormonal therapy; ADT + docetaxel; ADT + first-generation nonsteroidal antiandrogen; or ADT alone. RESULTS: We analyzed 2226 Black and 16,071 White Medicare, and 1020 Black and 2364 White VHA patients. TI was significantly lower for Black vs White Medicare patients overall (adjusted odds ratio [OR] 0.68; 95% confidence interval [CI] 0.58-0.81) and without Medicaid (adjusted OR 0.70; 95% CI 0.57-0.87). Medicaid patients had less TI irrespective of race. OS was worse for Black vs White Medicare patients overall (adjusted hazard ratio [HR] 1.20; 95% CI 1.09-1.31) and without Medicaid (adjusted HR 1.13; 95% CI 1.01-1.27). OS was worse in Medicaid vs without Medicaid, with no significant OS difference between races. TI was significantly lower for Black vs White VHA patients (adjusted OR 0.75; 95% CI 0.61-0.92), with no significant OS difference between races. CONCLUSIONS: Guideline-recommended TI was low for all patients with mCSPC, with less TI in Black patients in both Medicare and the VHA. Black race was associated with worse OS in Medicare but not the VHA. Medicaid patients had less TI and worse OS than those without Medicaid, suggesting poverty and race are associated with care and outcomes.

Prostate-specific antigen response and clinical progression-free survival in Black and White men with chemotherapy-naïve metastatic castration-resistant prostate cancer treated with enzalutamide in a real-world setting.

BACKGROUND: In the United States, Black men have a higher incidence of prostate cancer (PC)-related mortality than men of other races. Several real-world studies in advanced PC suggest, however, that Black men respond better to novel hormonal therapies than White men. Data on treatment responses to enzalutamide by race are limited. We assessed real-world prostate-specific antigen (PSA) response and clinical progression-free survival (cPFS) of Black vs. White men with chemotherapy-naïve PC treated with enzalutamide. METHODS: This retrospective cohort study included patients with PC who initiated enzalutamide treatment from 2014 to 2018 in the IntrinsiQ Specialty Solutions™ database, a collection of electronic medical records from community urology practices. Index date was the date of the first prescription for enzalutamide, used as a proxy for metastatic castration-resistant PC (mCRPC). Patients who had undergone chemotherapy and/or abiraterone therapy were excluded. Kaplan-Meier and Cox models adjusted for baseline characteristics were used to estimate PSA response and cPFS by race. RESULTS: The study included 214 Black and 1332 White men with chemotherapy-naïve PC presumed to have mCRPC based on the enzalutamide indication during the study period. Black men were younger and had higher baseline median PSA levels than White men. Enzalutamide therapy duration, follow-up time, and number of post-index PSA tests were similar between races. In multivariable analyses, the risk of patients achieving a ≥ 50% PSA decline was similar, whereas a numerically higher trend of ≥90% PSA decline was observed in Black men (HR 1.23; 95% CI 0.93-1.62 [P = 0.14]). In the multivariable analysis, Black men had significantly better cPFS (HR 0.82; 95% CI 0.68-0.98 [P = 0.03]). CONCLUSIONS: Black and White men with presumed chemotherapy-naïve mCRPC had similar PSA responses when treated with enzalutamide, but Black men had better cPFS than White men. Further research is warranted to validate these findings.

Treatment patterns and survival in metastatic castration-sensitive prostate cancer in the US Veterans Health Administration.

BACKGROUND: Limited real-world data exist on treatment patterns and outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: A retrospective cohort study was conducted, using the Veterans Health Administration claims database (April 2013-March 2018). Among 369,734 prostate cancer patients, we selected all men who developed metastases within 90 days before or after medical/surgical castration and who received androgen deprivation therapy (ADT). Patients were categorized into four cohorts: ADT-only (± <90-day nonsteroidal anti-androgen [NSAA] use), ADT + NSAA, ADT + docetaxel, and ADT + abiraterone. Main outcomes were treatment patterns, time-to-progression to metastatic castration-resistant disease, and overall survival. Multivariable analysis and sensitivity analysis were conducted. RESULTS: Of 1395 patients, 874 (63%) received ADT-only, 338 (24%) received ADT + NSAA, 108 (8%) received ADT + docetaxel, and 75 (5%) received ADT + abiraterone. Proportions on ADT-only and ADT + NSAA declined (from 66% to 60% and from 31% to 17%, respectively) over the study period, while proportions prescribed ADT + docetaxel or abiraterone increased from 3% to 9% and from 1% to 15%, respectively. Patients treated with ADT + NSAA had similar risks of castration-resistant disease (hazard ratio [HR] 1.05; 95% confidence interval [CI]: 0.87, 1.26) and overall mortality (HR 1.22; 95% CI: 0.97, 1.54) as ADT-only. CONCLUSIONS: Most patients with mCSPC initiating ADT received ADT-only or ADT + NSAA, despite the emergence of docetaxel and novel hormonal therapies. Even in the most recent period (2017 to early 2018), only 24% of men received intensified therapy with agents known to prolong survival versus ADT-only. These data in real-world clinical practice suggest substantial room for improved outcomes in patients with mCSPC.

How Oncologists Perceive the Availability and Quality of Information Generated From Patient-Reported Outcomes (PROs).

BACKGROUND: Despite increased incorporation of patient-reported outcome (PRO) measures into clinical trials, information generated from PROs remains largely absent from drug labeling and electronic health records, giving rise to concerns that such information is not adequately informing clinical practice. OBJECTIVE: To evaluate oncologists' perceptions concerning the availability and quality of information generated from PRO measures. Additionally, to identify whether an association exists between perceptions of availability and attitudes concerning quality. METHOD: An online, 11-item questionnaire was developed to capture clinician perspectives on the availability and use of PRO data to inform practice. The survey also asked respondents to rate information on the basis of 4 quality metrics: "usefulness," "interpretability," "accessibility," and "scientific rigor." RESULTS: Responses were received from 298 of 1301 invitations sent (22.9% response rate). Perceptions regarding the availability of PRO information differed widely among respondents and did not appear to be linked to practice setting. Ratings of PRO quality were generally consistent, with average ratings for the 4 quality metrics between "satisfactory" and "good." A relationship was observed between ratings of PRO data quality and perceptions of the availability. CONCLUSION: Oncologists' attitudes toward the quality of information generated from PRO measures are favorable but not enthusiastic. These attitudes may improve as the availability of PRO data increases, given the association we observed between oncologists' ratings of the quality of PRO information and their perceptions of its availability.

Health-related quality of life in patients with fully resected BRAFV600 mutation-positive melanoma receiving adjuvant vemurafenib.

AIM OF STUDY: The aim of the study was to assess the impact of treatment with adjuvant vemurafenib monotherapy on health-related quality of life (HRQOL) in patients with resected stage IIC-IIIC melanoma. METHODS: The phase 3 BRIM8 study (NCT01667419) randomised patients with BRAFV600 mutation-positive resected stage IIC-IIIC melanoma to 960 mg of vemurafenib twice daily or matching placebo for 52 weeks (13 × 28-day cycles). Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) version 3 at baseline, cycle 1 (days 1, 15 and 22), cycle 2 (days 1 and 15), day 1 of every subsequent 4-week cycle, the end-of-treatment visit and each visit during the follow-up period. RESULTS: Completion rates for the EORTC QLQ-C30 questionnaire were high (>80%). There was a mean decline in the global health status (GHS)/quality of life (QOL) score of 17.4 (±22.9) and 17.3 (±24.1) points at days 15 and 22 of cycle 1, respectively, among vemurafenib-treated patients who recovered to approximately 10 points below baseline for the remainder of the treatment period. A similar trend was observed in all functional scales except for cognitive function (<10-point change from baseline at all visits) and in the symptom scores for appetite loss, fatigue and pain. As observed for the GHS/QOL score, all scores rapidly returned to baseline after completion of planned vemurafenib treatment or treatment discontinuation. CONCLUSIONS: The schedule of HRQOL assessments allowed for an accurate and complete evaluation of the impact of acute treatment-related symptoms. Vemurafenib-treated patients experience clinically meaningful moderate worsening in some treatment- or disease-related symptoms and GHS/QOL that resolve over time.