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Objectives Caregivers of adult phase 1 oncology trial patients experience high levels of distress and face barriers to in-person supportive care. The Phase 1 Caregiver LifeLine (P1CaLL) pilot study assessed the feasibility, acceptability, and general impact of an individual telephone-based cognitive behavioral stress-management (CBSM) intervention for caregivers of phase I oncology trial patients. Methods The pilot study involved 4 weekly adapted CBSM sessions followed by participant randomization to 4 weekly cognitive behavioral therapy sessions or metta-meditation sessions. A mixed-methods design used quantitative data from 23 caregivers and qualitative data from 5 caregivers to examine the feasibility and acceptability outcomes. Feasibility was determined using recruitment, retention, and assessment completion rates. Acceptability was assessed with self-reported satisfaction with program content and participation barriers. Baseline to post-intervention changes in caregiver distress and other psychosocial outcomes were assessed for the 8-session intervention. Results The enrollment rate was 45.3%, which demonstrated limited feasibility based on an a priori criterion enrollment rate of 50%. Participants completed an average of 4.9 sessions, with 9/25 (36%) completing all sessions and an 84% assessment completion rate. Intervention acceptability was high, and participants found the sessions helpful in managing stress related to the phase 1 oncology trial patient experience. Participants showed reductions in worry and isolation and stress. Significance of results The P1CaLL study demonstrated adequate acceptability and limited feasibility and provided data on the general impact of the intervention on caregiver distress and other psychosocial outcomes. Caregivers of phase 1 oncology trial patients would benefit from supportive care services; a telephone-based intervention may have more utilization and thus make a larger impact.

Purpose: Immune checkpoint inhibitor and vascular endothelial growth factor receptor inhibitor combinations are effective treatments for patients with metastatic renal cell carcinoma (mRCC). This phase 1/2 clinical trial evaluated the safety and efficacy of pembrolizumab and cabozantinib in mRCC patients. Methods: Eligible patients had mRCC clear cell or non-clear cell histology, adequate organ function, ECOG 0-1, and no prior exposure to pembrolizumab or cabozantinib. The primary endpoint was objective response rate (ORR) at the recommended phase 2 dose (RP2D). Secondary endpoints included safety, disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Results: Forty-five patients were enrolled. 40 patients were treated at the RP2D of pembrolizumab 200 mg IV Q3W and cabozantinib 60 mg PO QD, 38 of which were evaluable for response. The ORR was 65.8% (95% CI, 49.9%-78.8%) for all evaluable patients [78.6% as 1L therapy, 58.3% as 2L therapy]. The DCR was 97.4% (95% CI, 86.5%-99.9%). Median DoR was 8.3 months (IQR 4.6-15.1). At a median follow-up of 23.54 months, the mPFS was 10.45 months (95% CI, 6.25-14.63) and mOS was 30.81 months (95% CI, 24.2-NR). The most common G1/G2 treatment-related adverse events (TRAE) were diarrhea, anorexia, dysgeusia, weight loss, and nausea. The most common G3/G4 TRAEs were hypertension, hypophosphatemia, ALT elevation, diarrhea, and fatigue. There was one G5 TRAE of reversible posterior encephalopathy syndrome related to cabozantinib. Conclusions: Pembrolizumab and cabozantinib treatment in mRCC patients demonstrated encouraging preliminary efficacy and a manageable toxicity profile comparable to other available CPI-TKI combinations.

In Colorado, medical aid in dying (MAiD) is legal, allowing a terminally ill person to request a prescription and self-administer a medication to end their life. Such requests are granted under certain circumstances, including a malignant neoplasm diagnosis, with a goal of peaceful death. This study examined differences in attitudes and actual participation in MAiD between oncologists and non-oncologists, using data from a recent survey of physicians regarding MAiD.

The majority of men with prostate cancer are diagnosed when they are older than 65 years; however, clinical trial participants are disproportionately younger and more fit than the real-world population treated in typical clinical practices. It is, therefore, unknown whether the optimal approach to prostate cancer treatment is the same for older men as it is for younger and/or more fit men. Short screening tools can be used to efficiently assess frailty, functional status, life expectancy, and treatment toxicity risk. These risk assessment tools allow for targeted interventions to increase a patient's reserve and improve treatment tolerance, potentially allowing more men to experience the benefit of the significant recent treatment advances in prostate cancer. Treatment plans should also take into consideration each patient's individual goals and values considered within their overall health and social context to reduce barriers to care. In this review, we will discuss evidence-based risk assessment and decision tools for older men with prostate cancer, highlight intervention strategies to improve treatment tolerance, and contextualize these tools within the current treatment landscape for prostate cancer.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known.In this phase 3, randomized, open-label trial, we randomly assigned adults with previously untreated clear-cell, advanced renal-cell carcinoma to receive either nivolumab (240 mg every 2 weeks) plus cabozantinib (40 mg once daily) or sunitinib (50 mg once daily for 4 weeks of each 6-week cycle). The primary end point was progression-free survival, as determined by blinded independent central review. Secondary end points included overall survival, objective response as determined by independent review, and safety. Health-related quality of life was an exploratory end point.Overall, 651 patients were assigned to receive nivolumab plus cabozantinib (323 patients) or sunitinib (328 patients). At a median follow-up of 18.1 months for overall survival, the median progression-free survival was 16.6 months (95% confidence interval [CI], 12.5 to 24.9) with nivolumab plus cabozantinib and 8.3 months (95% CI, 7.0 to 9.7) with sunitinib (hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.64; P0.001). The probability of overall survival at 12 months was 85.7% (95% CI, 81.3 to 89.1) with nivolumab plus cabozantinib and 75.6% (95% CI, 70.5 to 80.0) with sunitinib (hazard ratio for death, 0.60; 98.89% CI, 0.40 to 0.89; P = 0.001). An objective response occurred in 55.7% of the patients receiving nivolumab plus cabozantinib and in 27.1% of those receiving sunitinib (P0.001). Efficacy benefits with nivolumab plus cabozantinib were consistent across subgroups. Adverse events of any cause of grade 3 or higher occurred in 75.3% of the 320 patients receiving nivolumab plus cabozantinib and in 70.6% of the 320 patients receiving sunitinib. Overall, 19.7% of the patients in the combination group discontinued at least one of the trial drugs owing to adverse events, and 5.6% discontinued both. Patients reported better health-related quality of life with nivolumab plus cabozantinib than with sunitinib.Nivolumab plus cabozantinib had significant benefits over sunitinib with respect to progression-free survival, overall survival, and likelihood of response in patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol Myers Squibb and others; CheckMate 9ER ClinicalTrials.gov number, NCT03141177.).

OBJECTIVES: Advanced bladder cancer (ABC) disproportionately affects older adults, and little is known about older patients’ priorities for care planning in advanced cancer. Patient-centered communication remains crucial to shared decision-making between patients, families, and providers. Yet, older patients with cancer may not always know how to express their preferences, and oncologists do not always review patients’ informational needs. This study aimed to understand preferences of older patients with ABC related to their communication with providers and navigation of care planning. MATERIALS AND METHODS: This qualitative descriptive study involved in-depth interviews and focus groups with older patients with ABC and their care partners, which explored their priorities for care planning and communication with providers, decision-making processes, and valued traits in ABC care. Data were analyzed using thematic analysis. RESULTS: Ten participants attended focus groups or interviews. Seven patients were male and three care partners were female. The mean age was 74. Time since ABC diagnosis ranged from three to seventeen months. Four key themes illustrate participants’ priorities in their ABC care as older adults: 1. The significance of key phrasing in communication from oncologists, 2. The need for clear expectation-setting about prognosis and treatment, 3. The role of others in patient care decisions, and 4. Valued traits in care communication. CONCLUSION: Older patients with ABC and their care partners are active participants in their care. Oncologists should prioritize setting clear expectations for treatment, involving family in care planning, and communicating honestly about expected changes to quality of life and functional status.

Background: Following a prostate cancer (PC) diagnosis, treatment-related symptoms may result in diminished quality of life (QoL). Improved diet and increased exercise may improve QoL in men with PC. Methods: We conducted a 4-arm pilot randomized trial to assess feasibility and acceptability of a 3-month web-based diet and exercise intervention, among men (>18 years of age) with PC (reported elsewhere). The purpose of this study is to describe the change in QoL measured by surveys (eg, QLQ-C30, PROMIS Fatigue) at enrollment and following the intervention. Men were randomized 1:1:1:1 to increasing levels of web-based behavioral support: Level 1: website; Level 2: Level 1 plus personalized diet and exercise prescription; Level 3: Levels 1-2 plus Fitbit and text messages; Level 4: Levels 1-3 plus 2 30-minute coaching calls. T-tests were used to compare pre-post change in mean QoL scores between each Level and Level 1. Results: Two hundred and two men consented and were randomized (n = 49, 51, 50, 52 for Levels 1-4, respectively). Men were predominantly white (93%), with a median age of 70 years (Intra-quartile Range [IQR]: 65,75) and 3 years (IQR: 1,9) post primary treatment for mostly localized disease (74% with T1-2). There were no meaningful changes in QoL, but there were notable trends. Level 3 participants had small improvements in QLQ-C30 Global Health (5.46; 95% CI: −0.02, 10.95) compared to Level 1. In contrast, Level 2 participants trended toward decreasing Global QoL (−2.31, 95% CI: −8.05, 3.42), which may reflect declines in function (eg, Cognitive: −6.94, 95% CI: −13.76, −0.13) and higher symptom burden (eg, Diarrhea: 4.63, 95% CI: −1.48, 10.74). Conclusions: This short, web-based intervention did not appear to have an impact on PC survivors’ QoL. Most men were several years past treatment for localized disease; the potential for this approach to reduce symptoms and improve QoL in men who have worse health may still be warranted.

188 Background: Metastatic castration-resistant prostate cancer (mCRPC) becomes resistant to anti-androgen therapies due to a variety of adaptive mechanisms. Intramuscular bipolar androgen therapy (BAT) which alternates between high and low testosterone (T) levels is therapeutically active in mCRPC and confers sensitivity to second-generation androgen receptor antagonists such as enzalutamide (ENZA). We hypothesized that transdermal T with sustained supraphysiologic T levels would lead to high response rates to ENZA in mCRPC. We also hypothesized Square-wave transdermal T therapy would be a safe alternative to BAT due to the ability to quickly withdraw therapy in the setting of symptoms. Methods: This was an open-label, single-site, phase 2 feasibility trial in men with asymptomatic mCRPC who had not previously received ENZA. Transdermal T was administered at a dose of 100 mg/day for a minimum of 12 weeks and until disease progression. Therapy was then switched to ENZA 160 mg/day until next disease progression. Patients who initially responded to T could receive a second course of transdermal T followed by ENZA, remaining on study until progression on both T and ENZA, or for the 12-month study duration, whichever was sooner. ADT was continued throughout. The primary endpoint of the study was feasibility. T dose was adjusted to achieve T levels between 900-1500 ng/dL. Secondary end points included PSA50 response rate (50% decline in PSA) and safety. Results: Fifteen patients were enrolled. Ten (66.7%) had Gleason >8 disease. Thirteen (86.7%) patients had bone metastases. Median baseline PSA was 11.73 ng/mL. Primary endpoint of feasibility based on patient recruitment and retention was met. The median testosterone level on T was 901.3 ng/dL (Range: 645.2 to 1171.1). Median time on therapy was 15.9 weeks on T and 25.9 weeks on ENZA. PSA50 was 13.3% on initial T therapy and 66.7% after switching to ENZA. Three (20%) patients did not initiate ENZA after T progression. Two desired to avoid androgen-related side effects and 1 initiated chemotherapy. No Grade 3 or higher adverse events (AEs) occurred on T and the most common AEs were weight gain, rash, and nipple sensitivity. Conclusions: Square-wave transdermal T alternating with ENZA is feasible and achieves adequate T levels in the treatment of asymptomatic mCRPC. Given the acceptable safety profile and quick reversibility, transdermal T warrants further exploration, and we have expanded enrollment to include higher risk patient populations. Clinical trial information: NCT03734653 .

Physicians who participate in medical-aid-in-dying (MAID) cannot be easily identified and studied due to cost and anonymity barriers. We developed and empirically tested a novel methodology to identify and survey physicians highly likely to participate in MAID activities. We used a state-level comprehensive administrative claims database to identify a cohort of patients with diagnoses and hospice enrollment similar to those known to have filled a prescription for MAID from 2017–2018. We then identified physicians who provided routine outpatient care to these patients using National Provider Identifier numbers. We surveyed these physicians in 3 waves (n = 583 total surveys), ranking physicians in order of their likelihood of being asked about MAID for each wave based on characteristics including specialty and the number of unique patients they had provided care to. We re-ranked physicians in waves 2 and 3 based on responses from prior waves. Physicians were surveyed only once and there was no follow-up to preserve anonymity. Surveys assessed the proportion of respondents who participated in MAID activities (discussions, referrals, and/or prescriptions). We identified 6369 physicians that provided care to 2960 patients. In survey waves one, two, and three respectively, response rates (55%, 52%, and 55%; p = 0.98) and the proportion of respondents that participated in MAID activities (58%, 56%, and 42%; p = 0.05) were similar. Small adjustments made to physician ranking criteria in waves two and three did not increase the proportion of physicians that participated in MAID activities. We used a novel methodology using administrative data to identify and survey physicians at high likelihood of participating in MAID activities. We achieved good overall response rates (52%), and a high proportion of respondents that participated in MAID activities (52%), demonstrating that it is possible to overcome cost and anonymity barriers to conducting quantitative research on MAID. This methodology could be used in larger scale studies of MAID or other bioethical issues with “hidden” physician populations.

Prostate cancer is the second most common cancer in men in the USA and several studies suggest more aggressive disease in older patients. However, screening remains controversial, especially in the older patient population. Aggressive prostate cancers are more common in older men. Screening trial results are conflicting but data suggest an improvement in prostate cancer mortality and increased detection of metastatic disease with screening. When PSA is utilized with multiparametric MRI and biomarker assays, patients at significant risk of clinically meaningful prostate cancer can be appropriately selected for biopsy. A thoughtful and individualized approach is central when considering prostate cancer screening in older men. This approach includes life expectancy estimation, use of appropriate geriatric assessment tools, use of multiparametric MRI and biomarkers in addition to PSA, and most importantly shared decision-making with patients.

Adult Wilms tumor (WT) is a well-known, albeit rare entity and has historically been associated with worse overall clinical outcomes when compared to younger patients. Because WT is uncommon in adult patients, it is often misdiagnosed and treated off standardized pediatric protocols. WT associated with pregnancy is even more rare, and there is not a standardized approach to this small subset of patients. We present a case of an adult WT discovered and managed during the perinatal period and review prior published cases.

5087 Background: Clinical trials can provide access to novel systemic agents and possible improved survival for men diagnosed with regional and metastatic prostate cancer. Although clinical trials should be accessible to all patient populations, racial disparities to enrollment of clinical trials and its outcomes remain an important unknown outcome. Herein, we sought to elucidate the racial disparities in clinical trial enrollment and survival amongst advanced prostate cancer patients from a large community-based medical oncology consortium. Methods: Using CancerLinQ, we identified all patients who were diagnosed with regional (N1+) and/or metastatic (M1) prostate cancer from 2011 – 2021. Enrollment into a clinical trial and overall survival constituted the primary outcomes in this study. Multivariable logistic regression and Cox proportional hazard regression were used to identify covariates associated with each outcome. Results: Amongst the 160,888 patients with regional/metastatic prostate cancer, only 1.5% patients were enrolled in a clinical trial (n = 2,368). On multivariable analysis, patients with worse ECOG performance status were associated with lowers odds of clinical trial enrollment (p < 0.001). Relative to white patients, African-American men (AAM) also had lower odds of clinical trial enrollment (OR: 0.67; p < 0.001). For the entire cohort, clinical trial enrollment correlated with higher survival (HR: 1.19; p < 001) and lower survival for AAM men (HR: 0.85; p < 0.001) compared to white men after adjusting for other covariates. In the subgroup analysis of patients enrolled in clinical trials, AAM demonstrated similar survival to white patients (HR: 0.96, p = 0.95). Conclusions: Although African-American men with regional/metastatic prostate cancer face barriers to clinical trial enrollment, racial disparities in survival appear to resolve for patients who enroll in clinical trials. Increased attention is needed to address barriers to communication and access to clinical trials.

e16557 Background: Fosciclopirox (F) is being developed for the treatment of non-muscle invasive (NMIBC) and muscle invasive (MIBC) bladder cancer. F is a prodrug which is rapidly and completely metabolized in blood to its active metabolite, ciclopirox (CPX). In preclinical models of bladder cancer, CPX acts in part as a γ-secretase inhibitor by binding to γ-secretase complex proteins Presenilin 1 and Nicastrin, resulting in Notch and Wnt inhibition. The F Recommended Phase 2 Dose (RP2D), 900 mg/m2 administered IV over 20 minutes, was identified in the Phase 1 dose escalation trial (NCT03348514) in advanced solid tumor patients. Methods: The F RP2D was investigated in two early phase NMIBC and MIBC clinical proof of concept trials. In NCT04608045, neoadjuvant F was administered as monotherapy in cisplatin-ineligible (C-I) MIBC patients and in combination with gemcitabine + cisplatin in chemotherapy-eligible (C-E) MIBC patients. Clinical stage was assessed in pre-treatment (TURBT/CT) and post-treatment pathological state determined at radical cystectomy, (RC). The steady-state plasma and urine pharmacokinetics of F were also characterized. In NCT04525131, F was administered once daily for five days prior to TURBT. Pre- and post-treatment (at TURBT) bladder tumor samples underwent single cell sequencing to identify treatment effects on gene expression. Plasma, urine, and bladder tumor concentrations of F and its metabolites were determined in samples collected at TURBT. Results: Five C-E and 4 C-I MIBC patients received neoadjuvant F prior to RC. Twelve NMIBC patients received F prior to TURBT. There were no treatment-related serious adverse events observed in either study. Each patient experienced at least one treatment-emergent adverse event (TEAE), none of which resulted in study discontinuation. The most common TEAEs were nausea, fatigue, and constipation. Pathologic downstaging (< ypT2) of bladder tumors was observed in 3 C-E MIBC patients with 2 CRs (ypT0). Two of 4 C-I patients had evident clinical response by CT scan with only microscopic residual ypT2 disease. Treatment-related changes in expression of Notch 1, Notch 2, Hes 1, Hey-1, c-Myc, ß-catenin and survivin were observed in the majority of NMIBC patients. F disappeared from plasma within 2 hours of administration. The mean CPX elimination half-life of CPX, apparent systemic clearance, and volume of distribution values were 8.8 hours, 46 L/hr and 549 L, respectively. Mean plasma, tumor and urine concentrations of CPX at TURBT were approximately 27, 9 and 100 µM, respectively. Conclusions: To date, fosciclopirox is well tolerated and achieves sufficient systemic, tumor, and urine CPX exposure at the RP2D. Evidence of target inhibition was demonstrated in NMIBC tumors and preliminary signs of clinical activity observed in MIBC patients. Safety and efficacy trials are planned to confirm and expand findings in NMIBC and MIBC patients. Clinical trial information: NCT04608045; NCT04525131.

e16509 Background: Immune-mediated adverse events (irAEs) can be seen in patients (pts) receiving checkpoint inhibitors (CPI). It is unknown whether the immune response to vaccines against Sars-CoV-2 interacts with the immune activation from CPI therapy. In this retrospective study, we examined the incidence of severe irAEs in pts with renal cell carcinoma (RCC) who received vaccines against Sars-CoV-2 during the course of their CPI therapy. Methods: Following IRB approval, RCC pts who received any CPI treatment since FDA authorization of the first COVID-19 vaccine in March 2021 were identified via institutional electronic health record. Pts who received one or more doses of an authorized vaccine within 60 days of CPI treatment were included. The primary endpoint was to evaluate the incidence of severe irAE (defined as one or more of the following: grade 3 AE or above, multi-system involvement, need for hospitalization). Secondary endpoints included time between CPI and vaccination, need for immunosuppressive therapy, and rate of discontinuation. Data was analyzed using descriptive statistics. Results: Sixty-five pts were included in our analysis with a median age of 66 years (IQR: 58.0, 73.0); 80% pts were male. At the time of vaccination, 26 pts (40.0%) received CPI monotherapy, 12 pts (18.4%) received combination (combo) CPI therapy, and 27 pts (41.6%) received combo therapy with a tyrosine kinase inhibitor (TKI) and CPI. The type of vaccine received was Pfizer Bio-N-Tech in 30 pts (46.2%), Moderna in 33 pts (50.7%), and Johnson and Johnson in 2 pts (3.1%). Six pts received only one vaccination (9.2%), 18 pts received two vaccinations (27.7%), and 40 pts received 3 or more vaccinations (61.5%). Eleven pts (16.9%) experienced severe irAEs following vaccination. Rates of severe irAEs was 3.8% (1/26) with CPI monotherapy, 25% (3/12) with combo CPI, and 25.9% (7/27) with combo CPI and TKI. Severe irAEs occurred after the first vaccine dose in 4 pts (36.4%), second dose in 3 pts (27.3%), and third dose in 4 pts (36.4%) pts. The median time between CPI treatment and vaccination in this group was 11.0 days (IQR: 7.5-15.5). Hospitalization was required for 6 patients (54.5%). Ten pts (90.9%) required immunosuppressive therapy with a median steroid duration of 85.5 days (IQR 36.8, 176.0). Six pts (54.5%) discontinued CPI therapy following severe irAEs. Conclusions: In this retrospective study, the observed rate of severe irAEs in RCC patients who received CPI and COVID-19 vaccine concomitantly was similar to historical controls, suggesting that there is no definite increase in the incidence of severe irAEs in pts undergoing CPI therapy and receiving COVID-19 vaccination. Future confirmatory studies are warranted. Supported by the Health Data Compass Data Warehouse project (healthdatacompass.org)

Prostate cancer is the second most common cancer in men in the USA and several studies suggest more aggressive disease in older patients. However, screening remains controversial, especially in the older patient population.Aggressive prostate cancers are more common in older men. Screening trial results are conflicting but data suggest an improvement in prostate cancer mortality and increased detection of metastatic disease with screening. When PSA is utilized with multiparametric MRI and biomarker assays, patients at significant risk of clinically meaningful prostate cancer can be appropriately selected for biopsy. A thoughtful and individualized approach is central when considering prostate cancer screening in older men. This approach includes life expectancy estimation, use of appropriate geriatric assessment tools, use of multiparametric MRI and biomarkers in addition to PSA, and most importantly shared decision-making with patients.

With growing support of perioperative chemotherapy for upper tract urothelial carcinoma (UTUC), current biopsy methods are challenging, and little is known as to the degree to which patients would appropriately receive neoadjuvant chemotherapy (NAC) from biopsy alone. Herein, we sought to assess the rates of appropriate clinical use of NAC and identify clinicopathologic factors associated with aggressive UTUC amongst patients undergoing radical nephroureterectomy (RNU) for clinically localized disease.From 2004 to 2013, we identified all treatment naïve patients diagnosed with clinically localized, high grade UTUC (cTa-4Nx) who underwent RNU from the National Cancer Database (NCDB). Pathologic criteria for NAC (pT2-4N0,x; pTanyN1) from RNU represented the primary outcome. Bivariate and multivariable analyses were utilized to identify covariates associated with primary outcome to determine appropriate use of NAC.During the study interval, 5,362 patients were diagnosed with clinically localized UTUC and underwent RNU. Overall, 49.1% of patients presented with an unknown primary tumor stage (Tx) and 24.5% had invasive UTUC from biopsy. On multivariable analysis, upper tract tumor size was associated with invasive UTUC eligible for NAC (all P0.05). Amongst patients with cTx UTUC from biopsy, half of patients had pathologic noninvasive UTUC (pTa,is,1) from RNU and would be overtreated with NAC.Significant uncertainty persists in assigning primary upper tract tumor depth and represents a key barrier to widespread implementation of NAC for patients with high grade UTUC. Further research is needed to more accurately determine clinical criteria to identify patients for NAC.

Background Diet and exercise may be associated with quality of life and survival in men with prostate cancer. Objective This study aimed to determine the feasibility and acceptability of a remotely delivered web-based behavioral intervention among men with prostate cancer. Methods We conducted a multi-site 4-arm pilot randomized controlled trial of a 3-month intervention (TrueNTH Community of Wellness). Eligibility included self-reported prostate cancer diagnosis, having a personal device that connected to the internet, age ≥18 years, and ability to read English and receive text messages and emails. Men receiving chemotherapy or radiation, or those who reported contraindications to exercise, could participate with physician clearance. Participants were randomized (1:1:1:1) to additive intervention levels: website; website and personalized diet and exercise prescription; website, personalized prescription, Fitbit, and text messages; and website, personalized prescription, Fitbit, text messages, and 2 30-minute phone calls—one with an exercise trainer and one with a registered dietician. Primary outcomes were feasibility (accrual and attrition) and acceptability (survey data and website use). We described self-reported diet and exercise behavior at the time of enrollment, 3 months, and 6 months as secondary outcomes. Results In total, 202 men consented and were randomized between August 2017 and September 2018 (level 1: 49, level 2: 51, level 3: 50, level 4: 52). A total of 160 men completed the onboarding process and were exposed to their randomly assigned intervention (38, 38, 42, and 42 in levels 1, 2, 3, and 4, respectively). The follow-up rate was 82.7% (167/202) at 3 months and 77.2% (156/202) at 6 months. Participants had a median age of 70 years and were primarily White and college educated. Website visit frequency over the 3-month intervention period increased across levels (median: 2, 9, 11, and 16 visits for levels 1, 2, 3, and 4, respectively). Most were satisfied or very satisfied with the intervention (20/39, 51%; 27/42, 64%; 23/44, 52%; and 27/42, 64% for levels 1, 2, 3, and 4, respectively). The percentage of men who reported being very satisfied was highest among level 4 participants (10/42, 24% vs 4/39, 10%; 5/42, 12%; and 5/44, 11% for levels 1, 2, and 3, respectively). Dissatisfaction was highest in level 1 (5/39, 13% vs 1/42, 2%; 3/44, 7%; and 2/42, 5% for levels 2, 3, and 4, respectively). We observed small improvements in diet and physical activity at 3 months among men in level 4 versus those in level 1. Conclusions A web-based, remotely delivered, tailored behavioral intervention for men with prostate cancer is feasible. Future studies are warranted to increase the effect of the intervention on patient behavior while maintaining sustainability and scalability as well as to design and implement interventions for more diverse populations. Trial Registration ClinicalTrials.gov NCT03406013; http://clinicaltrials.gov/ct2/show/NCT03406013

Importance Central Nervous System (CNS) metastasis from prostate cancer (PCA) is a rare event, but one with significant prognostic impact for those affected. There are limited data on its impact in contemporary cohorts treated with modern agents. Design A retrospective institutional review was performed to characterize the occurrence/outcome of PCA CNS metastasis on all cases of PCA from 2011-2017. A manual chart review was performed to confirm PCA CNS metastases in all cases identified through a diagnostic code screening of the health data. Results 6,596 cases of PCA were identified, with 29 (20 dural and 9 intraparenchymal) confirmed cases of CNS metastases from prostate cancer. The median survival from the time of diagnosis of CNS metastasis was 2.6 (95%CI: 2.04 – 10.78) months and 5.41 (95% CI: 3.03 – not reached) months for dural and parenchymal metastases respectively. Among those who developed CNS metastases, approximately 79% of patients had prior exposure to abiraterone and/or enzalutamide, of whom 50% had ≥6 months of exposure. Four of the 5841 (0.07%) patients developed CNS metastases prior to the initiation of therapy or on androgen deprivation therapy (ADT) alone. In contrast, 24 of the 279 (8.6%) patients with 2 or more lines of medical therapy developed CNS metastases. Conclusions and Relevance: Our analysis highlights the continued poor prognosis of parenchymal and dural CNS metastases from PCA. CNS metastases in prostate cancer remain a rare event with a 0.4% incidence in this series, but this incidence is considerably increased in patients who receive medical therapy beyond first line ADT.

BACKGROUND Diet and exercise may be associated with quality of life and survival in men with prostate cancer. OBJECTIVE This study aimed to determine the feasibility and acceptability of a remotely delivered web-based behavioral intervention among men with prostate cancer. METHODS We conducted a multi-site 4-arm pilot randomized controlled trial of a 3-month intervention (TrueNTH Community of Wellness). Eligibility included self-reported prostate cancer diagnosis, having a personal device that connected to the internet, age ≥18 years, and ability to read English and receive text messages and emails. Men receiving chemotherapy or radiation, or those who reported contraindications to exercise, could participate with physician clearance. Participants were randomized (1:1:1:1) to additive intervention levels: website; website and personalized diet and exercise prescription; website, personalized prescription, Fitbit, and text messages; and website, personalized prescription, Fitbit, text messages, and 2 30-minute phone calls—one with an exercise trainer and one with a registered dietician. Primary outcomes were feasibility (accrual and attrition) and acceptability (survey data and website use). We described self-reported diet and exercise behavior at the time of enrollment, 3 months, and 6 months as secondary outcomes. RESULTS In total, 202 men consented and were randomized between August 2017 and September 2018 (level 1: 49, level 2: 51, level 3: 50, level 4: 52). A total of 160 men completed the onboarding process and were exposed to their randomly assigned intervention (38, 38, 42, and 42 in levels 1, 2, 3, and 4, respectively). The follow-up rate was 82.7% (167/202) at 3 months and 77.2% (156/202) at 6 months. Participants had a median age of 70 years and were primarily White and college educated. Website visit frequency over the 3-month intervention period increased across levels (median: 2, 9, 11, and 16 visits for levels 1, 2, 3, and 4, respectively). Most were satisfied or very satisfied with the intervention (20/39, 51%; 27/42, 64%; 23/44, 52%; and 27/42, 64% for levels 1, 2, 3, and 4, respectively). The percentage of men who reported being very satisfied was highest among level 4 participants (10/42, 24% vs 4/39, 10%; 5/42, 12%; and 5/44, 11% for levels 1, 2, and 3, respectively). Dissatisfaction was highest in level 1 (5/39, 13% vs 1/42, 2%; 3/44, 7%; and 2/42, 5% for levels 2, 3, and 4, respectively). We observed small improvements in diet and physical activity at 3 months among men in level 4 versus those in level 1. CONCLUSIONS A web-based, remotely delivered, tailored behavioral intervention for men with prostate cancer is feasible. Future studies are warranted to increase the effect of the intervention on patient behavior while maintaining sustainability and scalability as well as to design and implement interventions for more diverse populations. CLINICALTRIAL ClinicalTrials.gov NCT03406013; http://clinicaltrials.gov/ct2/show/NCT03406013

BACKGROUND Exercise and a healthy diet can improve the quality of life and prognosis of prostate cancer survivors, but there have been limited studies on the feasibility of web-based lifestyle interventions in this population. OBJECTIVE This study aims to develop a data-driven grounded theory of web-based engagement by prostate cancer survivors based on their experience in the Community of Wellness, a 12-week randomized clinical trial designed to support healthy diet and exercise habits. METHODS TrueNTH’s Community of Wellness was a four-arm pilot study of men with prostate cancer (N=202) who received progressive levels of behavioral support (level 1: website; level 2: website with individualized diet and exercise recommendations; level 3: website with individualized diet and exercise recommendations, Fitbit, and text messages; and level 4: website with individualized diet and exercise recommendations, Fitbit and text messages, and separate phone calls with an exercise trainer and a registered dietitian). The primary aim of the study is to determine the feasibility and estimate the effects on behaviors (results reported in a separate paper). Following the 12-week intervention, we invited participants to participate in 4 focus groups, one for each intervention level. In this report, we used grounded theory analyses including open, axial, and selective coding to generate codes and themes from the focus group transcripts. Categories were refined across levels using embodied categorization and constant comparative methods. RESULTS In total, 20 men with prostate cancer participated in the focus groups: 5, 4, 5, and 6 men in levels 1, 2, 3, and 4, respectively. Participants converged on 5 common factors influencing engagement with the intervention: environment (home environment, competing priorities, and other lifestyle programs), motivation (accountability and discordance experienced within the health care system), preparedness (technology literacy, health literacy, trust, and readiness to change), program design (communication, materials, and customization), and program support (education, ally, and community). Each of these factors influenced the survivors’ long-term impressions and habits. We proposed a grounded theory associating these constructs to describe the components contributing to the intuitiveness of a web-based lifestyle intervention. CONCLUSIONS These analyses suggest that web-based lifestyle interventions are more intuitive when we optimize participants’ technology and health literacy; tailor interface design, content, and feedback; and leverage key motivators (ie, health care providers, family members, web-based coach) and environmental factors (ie, familiarity with other lifestyle programs). Together, these grounded theory–based efforts may improve engagement with web-based interventions designed to support prostate cancer survivorship.

Background Exercise and a healthy diet can improve the quality of life and prognosis of prostate cancer survivors, but there have been limited studies on the feasibility of web-based lifestyle interventions in this population. Objective This study aims to develop a data-driven grounded theory of web-based engagement by prostate cancer survivors based on their experience in the Community of Wellness, a 12-week randomized clinical trial designed to support healthy diet and exercise habits. Methods TrueNTH’s Community of Wellness was a four-arm pilot study of men with prostate cancer (N=202) who received progressive levels of behavioral support (level 1: website; level 2: website with individualized diet and exercise recommendations; level 3: website with individualized diet and exercise recommendations, Fitbit, and text messages; and level 4: website with individualized diet and exercise recommendations, Fitbit and text messages, and separate phone calls with an exercise trainer and a registered dietitian). The primary aim of the study is to determine the feasibility and estimate the effects on behaviors (results reported in a separate paper). Following the 12-week intervention, we invited participants to participate in 4 focus groups, one for each intervention level. In this report, we used grounded theory analyses including open, axial, and selective coding to generate codes and themes from the focus group transcripts. Categories were refined across levels using embodied categorization and constant comparative methods. Results In total, 20 men with prostate cancer participated in the focus groups: 5, 4, 5, and 6 men in levels 1, 2, 3, and 4, respectively. Participants converged on 5 common factors influencing engagement with the intervention: environment (home environment, competing priorities, and other lifestyle programs), motivation (accountability and discordance experienced within the health care system), preparedness (technology literacy, health literacy, trust, and readiness to change), program design (communication, materials, and customization), and program support (education, ally, and community). Each of these factors influenced the survivors’ long-term impressions and habits. We proposed a grounded theory associating these constructs to describe the components contributing to the intuitiveness of a web-based lifestyle intervention. Conclusions These analyses suggest that web-based lifestyle interventions are more intuitive when we optimize participants’ technology and health literacy; tailor interface design, content, and feedback; and leverage key motivators (ie, health care providers, family members, web-based coach) and environmental factors (ie, familiarity with other lifestyle programs). Together, these grounded theory–based efforts may improve engagement with web-based interventions designed to support prostate cancer survivorship.

350 Background: First-line nivolumab plus cabozantinib (N+C) demonstrated superiority over sunitinib (SUN) in the primary disclosure of the phase 3 CheckMate 9ER trial (NCT03141177; 10.6 months minimum follow-up; Choueiri TK et al. N Engl J Med 2021) in patients (pts) with advanced renal cell carcinoma (aRCC). Here, we report the preplanned final overall survival (OS) analysis with updated efficacy and safety in intent-to-treat (ITT) pts, and an exploratory assessment of target lesions by organ site after extended follow-up. Methods: Pts with aRCC (clear cell component) were randomized to N 240 mg every 2 weeks + C 40 mg once daily vs SUN 50 mg once daily (4 weeks of 6-week cycles). The primary endpoint was RECIST v1.1–defined progression-free survival (PFS) by blinded independent central review (BICR) in ITT pts; secondary endpoints included OS, objective response rate (ORR) by BICR, and safety. The preplanned final OS analysis was set to occur after observing 254 events. Maximal reduction of target lung, lymph node, kidney, and liver lesions were evaluated per BICR via post hoc exploratory analyses. Results: After 25.4 months minimum follow-up (median, 32.9 months) for OS in ITT pts, a total of 271 OS events occurred, and N+C continued to demonstrate OS improvement vs SUN (N = 323 vs 328; median 37.7 vs 34.3 months; HR 0.70 [95% CI 0.55–0.90]). PFS (median 16.6 vs 8.3 months; HR 0.56 [95% CI 0.46–0.68]) and ORR (55.7% [95% CI 50.1–61.2] vs 28.4% [95% CI 23.5–33.6]) benefits were maintained with N+C vs SUN, and 12.4% (N+C) vs 5.2% (SUN) of pts had a complete response. Median duration of response was 23.1 months with N+C vs 15.1 months with SUN. A higher percentage of pts experienced any reduction and ≥30% reduction from baseline with N+C vs SUN in target lesions at all organ sites assessed (Table). Among all treated pts, 97.2% (N+C; N = 320) vs 93.1% (SUN; N = 320) had a treatment-related adverse event (TRAE) of any grade (65.0% vs 54.1% had a grade ≥ 3 TRAE). Conclusions: N+C continued to provide survival improvement vs SUN among ITT pts in the final OS analysis, additionally PFS and ORR benefits with N+C were sustained with minimum 2-year follow-up. A higher proportion of pts experienced tumor shrinkage benefit with N+C vs SUN across all 4 organ sites assessed. No new safety signals emerged with extended follow-up in either arm. These results highlight N+C as a first-line treatment for pts with aRCC. Clinical trial information: NCT03141177. [Table: see text]

5 Background: Penile cancer is a rare malignancy that accounts for less than 1% of male cancers in the United States. Localized disease, particularly T1 tumors (no invasion the corpora spongiosum, corpora cavernosa or adjacent structures using the AJCC 7th edition staging system) are potentially curable with local surgery. We present the racial differences in survival outcomes for T1, penile cancer from the SEER database. Methods: From 2004 to 2016, we identified all patients with T1 (coded as T1, T1a, T1b),N0,M0 penile cancer in the SEER-18 database were included. Univariate Kaplan-Meier analysis and multivariable (adjusting for age, year of diagnosis, race, socioeconomic status, primary tumor site and type of surgery) Cox-Regression analysis were conducted to investigate prognostic variables for cancer specific survival (CCS). Results: A total of 4,406 patients were identified with penile cancer; 1,941 patients had T1 disease and were further evaluated (Table). On multivariable analysis, Black (HR: 1.72, CI 1.01- 2.94; p=0.046) and Hispanic individuals (HR: 2.15, CI 1.36- 3.40; p= 0.001) had worse CSS compared to the White men with T1 disease. Logistic regression analysis shows no difference in the application of primary surgical resection by race (p=0.065). In the univariate analysis, patients who underwent primary site surgery had better 5-year CSS (HR: 0.36, CI 0.22-0.60; p

Background Most oncology trainees are not taught about the needs of older patients, who make up the majority of patients with cancer. Training of health care providers is critical to improve the care of older adults with cancer. There is no consensus about which geriatric oncology (GO) competencies are important for medical oncology trainees. Our objective was to identify GO competencies medical oncology trainees should acquire during training. Materials and Methods A modified Delphi consensus of experts in oncology medical education and GO was conducted. Experts categorized at what training stage proposed competencies should be attained: internal medicine, oncology, or GO training. Consensus was obtained if two thirds of experts agreed on the training stage at which the competency should be attained. Results A total of 78 potential competencies were identified, of which 35 (44.9%) proposed competencies were felt to be appropriate to be acquired during oncology training. The majority of the identified competencies pertained to prescribing of systemic therapy (n = 12) and psychosocial and supportive care (n = 13). No competencies related to geriatric assessment were identified for acquisition during oncology training. Conclusion Experts in oncology education and geriatric oncology agreed upon a set of GO competencies appropriate for oncology trainees. These results provide the foundation for developing a GO curriculum for medical oncology trainees and will hopefully lead to better care of older adults with cancer. Implications for Practice The aging population will drive the projected rise in cancer incidence. Although aging patients make up the majority of patients diagnosed with cancer, oncologists rarely receive training on how to care for them. Training of health care providers is critical to improving the care of older adults with cancer. The results of this study will help form the foundation of developing a geriatric oncology curriculum for medical oncology trainees.

Urothelial carcinoma, or bladder cancer, is a malignancy that most commonly affects older patients. The median age at diagnosis is 73 years, and care of these patients requires consideration not just of the disease-related factors such as stage and histology, but also of patient-related factors. Many of these patients have concurrent medical morbidities and additional changes related to the aging process. Older patients with cancer are a unique population requiring additional considerations and assessment in treatment decision-making. It is important to look beyond chronologic age. The traditional treatment for advanced disease has relied on platinum-based chemotherapy. These multi-agent regimens require consideration of baseline organ function as well as competing conditions that may heighten toxicity. The advent of a new class of cancer therapeutics, the immune checkpoint inhibitors, has changed the care of patients with advanced disease considerably. These immunotherapeutics have been approved for treating patients with disease progression on chemotherapy, or those who are ineligible (or unfit) to receive cisplatin-based therapy. This expansion of the population of patients eligible for treatment has great applicability to the unique considerations in an older patient population. In general, these new immunotherapies are well tolerated and effective in this group of patients.

To evaluate usage trends and identify factors associated with proton beam therapy (PBT) compared to alternative forms of external beam radiation therapy (RT) (EBRT) for localized prostate cancer.The National Cancer Database was queried for men with localized (N0, M0) prostate cancer diagnosed between 2004 and 2013, treated with EBRT, with available data on EBRT modality (photon vs. PBT). Binary multiple logistic regression identified variables associated with EBRT modality.In total, 143,702 patients were evaluated with relatively few men receiving PBT (5,709 [4.0%]). Significant differences in patient and clinical characteristics were identified between those men treated with PBT compared to those treated with photon (odds ratio [OR]; 95% CI). Patients treated with PBT were generally younger (OR = 0.73; CI: 0.67-0.82), National Comprehensive Cancer Network low-risk compared to intermediate (0.71; 0.65-0.78) or high (0.44; 0.38-0.5) risk, white vs. black race (0.66; 0.58-0.77), with less comorbidity (Charlson-Deyo 0 vs. 2+; 0.70; 0.50-0.98), live in higher income counties (1.55; 1.36-1.78), and live in metropolitan areas compared to urban (0.21; 0.18-0.23) or rural (0.14; 0.10-0.19) areas. Most patients treated with PBT travelled more than 100 miles to the treatment facility. Annual PBT utilization significantly increased in both total number and percentage of EBRT over time (2.7%-5.6%; P0.001). PBT utilization increased mostly in men classified as National Comprehensive Cancer Network low-risk (4%-10.2%).PBT for men with localized prostate cancer significantly increased in the United States from 2004 to 2013. Significant demographic and prognostic differences between those men treated with photons and protons were identified.

Hospice utilization has the potential to improve quality of life for patients while also decreasing healthcare costs at end of life. Barriers to hospice utilization have been identified, but less is known about how patient, provider, and system domains influence one another. We use in-depth interviews with physicians to examine the social, cultural, and economic contexts of decision making and how physician and organizational domains influence patient decision making around hospice. We identify sources of delay in physicians advocating for hospice referrals for their late-life patients that show how patient, physician, and system factors interact. Our results reveal incentives to postpone discussion of hospice that are not fully captured in policy perspectives, clinical guidelines, or current research paradigms focused on individual domains of influence. Opportunities to address previously identified barriers to hospice will benefit from consideration of how seemingly separate domains function in an integrated social context.

Bladder cancer is an extremely common cancer that primarily affects individuals aged >65 years. In caring for patients with bladder cancer, clinicians must also consider care of older persons in general. Management of muscle-invasive bladder cancer (MIBC) involves multidisciplinary treatment planning, because curative-intent therapy includes either surgery or radiation, with consideration of the role of systemic therapy. As clinicians develop a treatment plan, considering a geriatric oncology perspective may enhance patient care and influence outcomes for this large and growing population. Similarly, treatment plan development must also consider aspects unique to an older patient population, such as altered organ function, increased comorbidity, decreased functional reserve, and perhaps altered goals of treatment. Thus a thorough evaluation inclusive of disease assessment and geriatric assessment is essential to care planning. Population-based data show that as patients with MIBC age, use of standard therapies declines. Given the complexities of coordinating a multidisciplinary care plan, as well the complexities of treating a heterogeneous and potentially vulnerable older patient population, clinicians may benefit from upfront assessments to inform and guide the process. This review highlights the unique treatment planning considerations for elderly patients diagnosed with MIBC.

Data supporting neoadjuvant chemotherapy of high grade upper tract urothelial carcinoma are scant. In this multi-institution, prospective, phase II trial we investigated pathological complete responses after neoadjuvant chemotherapy of high grade upper tract urothelial carcinoma.Patients with high grade upper tract urothelial carcinoma in whom nephroureterectomy was planned were assigned to 4 neoadjuvant chemotherapy cycles of accelerated methotrexate, vinblastine, doxorubicin and cisplatin in those with baseline creatinine clearance greater than 50 ml per minute or gemcitabine and carboplatin in those with creatinine clearance 30 to 50 ml per minute or less. The study primary end point was a pathological complete response (ypT0N0). The accrual goal was 30 patients per arm. An 18% pathological complete response was considered worth further study while a 4% pathological complete response would not have justified pursuing this regimen. With 28 eligible patients per arm success was defined as 3 or more pathological complete responses (10.7%) in a given arm. Secondary end points included safety, renal function and oncologic outcomes.A total of 30 patients enrolled in the accelerated methotrexate, vinblastine, doxorubicin and cisplatin arm from 2015 to 2017. Six patients enrolled in the gemcitabine and carboplatin arm, which closed due to poor accrual. Of the 29 patients eligible for accelerated methotrexate, vinblastine, doxorubicin and cisplatin, including 23 men and 6 women with a median age of 65 years (range 40 to 84), 80% completed all planned treatments, 3 (10.3%) achieved ypT0N0 and 1 achieved ypT0Nx for a pathological complete response in 13.8% (90% CI 4.9-28.8). In 1 patient receiving accelerated methotrexate, vinblastine, doxorubicin and cisplatin nephroureterectomy was deferred due to grade 4 sepsis. The grade 3-4 toxicity rate was 23% in the accelerated methotrexate, vinblastine, doxorubicin and cisplatin arm with no grade 5 event.Accelerated methotrexate, vinblastine, doxorubicin and cisplatin neoadjuvant chemotherapy in patients with high grade upper tract urothelial carcinoma and creatinine clearance greater than 50 ml per minute was safe and demonstrated predefined activity with a 14% pathological complete response rate. Final pathological stage ypT1 or less in more than 60% of patients is encouraging. Together the results of this prospective trial support the use of neoadjuvant chemotherapy in eligible patients with high grade upper tract urothelial carcinoma.

Purpose Contemporary treatment for metastatic hormone sensitive prostate cancer (mHSPC) includes androgen deprivation therapy (ADT) plus abiraterone or docetaxel. While these intensified regimens have improved efficacy, they are also associated with increased cost and toxicities. Not all men with mHSPC may be candidates for these intensified regimens, yet there are no clinical models or biomarkers used to optimize treatment selection. Herein, we hypothesized that longer time from prior definitive therapy (DT), either radical prostatectomy, definitive radiotherapy, or both, to onset of metastatic disease is associated with improved survival outcomes in men with newly diagnosed mHSPC. Methods This multicenter retrospective study included men initiating systemic therapy with ADT for new mHSPC. Kaplan-Meier and COX proportional hazard models assessed time to metastatic castration-resistant prostate cancer (mCRPC) and overall survival (OS) by receipt of prior DT. Results Of the 253 men with new mHSPC, 115 (45%) had received prior DT. In a multivariate analysis, increasing years from DT to the start of ADT was an independent predictor of time to mCRPC (per year: hazard ratio 0.91 95% confidence interval 0.84–0.99, P = 0.020) and improved OS (per year: hazard ratio 0.87, 95% confidence interval 0.74–0.99, P = 0.0025) in patients with new mHSPC, and may assist with risk stratification in these patients at time of mHSPC. Conclusion Time from DT to start of ADT is an independent predictor of time to mCRPC and OS in men with new mHSPC, and may assist with risk stratification of these patients for systemic therapy selection.

4553 Background: First-line N+C significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) vs S in aRCC patients (pts) in the phase 3 CheckMate 9ER trial, leading to FDA approval of N+C in this setting. A deeper understanding of how baseline disease characteristics may impact clinical outcomes with N+C vs S may inform clinical decision making. Methods: Pts with clear cell aRCC were randomized to N 240 mg IV Q2W + C 40 mg PO QD vs S 50 mg PO QD (4 weeks of 6-week cycles). In this post hoc exploratory analysis, PFS, OS, and ORR were evaluated across pt subgroups defined by baseline IMDC risk status, organ sites of metastases (mets), number of organs with any lesions, or target lesion size. Consistent with primary/secondary efficacy endpoints in ITT pts, PFS and ORR were evaluated per RECIST v1.1 by blinded independent central review in subgroups. Results: Median follow-up in ITT pts was 23.5 months. PFS, OS, and ORR (including complete response [CR]) outcomes are summarized in the table across subgroups: IMDC risk (favorable [FAV], intermediate [I], poor [P]); number of organs with ≥ 1 target/nontarget lesion (T/NT; 1 and ≥ 2); sum of diameters of target lesions (sDTL; < and ≥ median [72.1 mm]), and in pts with liver, bone, or lung mets. The PFS HR favored N+C vs S and median (m) PFS was longer with N+C vs S across all subgroups. The OS HR also favored N+C vs S across most subgroups. ORR ranged from 38%–66% (N+C) vs 10%–44% (S) across subgroups, and CR benefits were seen with N+C in most subgroups. Additional outcomes including landmark OS and response details in subgroups will be reported. Conclusions: Consistent with outcomes in ITT pts, efficacy benefits with N+C vs S were observed regardless of IMDC risk status, organ site of mets, or extent of tumor burden at baseline. These results support N+C as a new first-line treatment option for pts with aRCC. Clinical trial information: NCT03141177. [Table: see text]

5034 Background: Alterations in DNA damage repair (DDR) genes are common in metastatic castration-resistant prostate cancer (mCRPC), and are implicated in responses to carboplatin [carbo], PARP inhibitors and immunotherapeutics. Inhibitors of the ATR kinase, which is involved in the DDR response, have been demonstrated to have synergistic activity with platinum compounds in preclinical models. We therefore conducted a phase 2 study of the ATR inhibitor berzosertib [berzo]+carbo vs. docetaxel [doce]+carbo in mCRPC. Methods: Patients (pts) previously treated with at least one secondary hormonal therapy and taxane underwent mandatory pre-treatment biopsy and were randomized 1:1 to receive Arm A (doce 60 mg/m2 day 1 + carbo AUC 4 day 1) or Arm B (berzo 90 mg/m2 days 2,9 + carbo AUC 5 day 1) every 21 days. Pts randomized to Arm A who were not candidates for doce received carbo AUC 5 monotherapy. Stratification factors were 1) prior PARP inhibitor (yes vs. no) and 2) evaluable disease by RECIST 1.1 (yes vs. no). Pts on Arm A crossed over to Arm B (berzo+carbo) at the earlier of PSA or radiographic progression. The primary endpoint was overall response rate (ORR; PSA reduction by ≥ 50% or radiographic response by RECIST 1.1). Secondary endpoints included time to PSA progression, radiographic PFS (rPFS), PFS by PCWG3 criteria, and adverse events (AEs) in each arm. Planned enrollment was 136 pts (for 130 to be treated), with interim analysis for futility after 65 pts were treated. Results: 73 pts were randomized between 6/2019 and 7/2020; 34 pts were treated on Arm A (26 carbo+doce; 8 carbo alone) and 31 on Arm B. Median number of prior systemic therapies (excluding ADT, 5α-reductase inhibitors, 1st generation antiandrogens) was 4 (range 2-8). Median treatment duration was 3 cycles, and 4 pts in each arm discontinued for AEs. Grade 3 or higher treatment-related AEs (TrAE) were seen in 13(38%) pts in Arm A and 21(68%) in Arm B. Pts in Arm B had greater frequency of grade 3-4 thrombocytopenia (8[26%] vs. 3[9%]). 1 pt in Arm B had grade 5 sepsis attributed to study treatment. ORR was 15% in Arm A (5/34; 5/26[19%] in pts who received carbo+doce) and 0% in Arm B (0/31). 14 pts in Arm A crossed over, with no subsequent responses seen. Median rPFS was 2.1(95% CI:2.0,3.2) mo in Arm A and 2.4(1.9,4.2) mo in Arm B. At planned interim analysis, trial enrollment and crossover to Arm B were halted due to futility. Conclusions: Carbo+berzo led to fewer overall responses and a higher rate of grade 3 or higher TrAEs compared to carbo+doce. All responses seen were in pts who received carbo+doce despite requirement for prior progression on taxane, suggesting that this combination is favored over carbo+berzo or carbo monotherapy in a heavily pre-treated biomarker-unselected population. Extensive genetic and molecular studies for DDR assessment from tissue and cfDNA are in progress. Clinical trial information: NCT03517969.

4544 Background: Checkpoint inhibitors (CPI) and vascular endothelial growth factor receptor inhibitors (VEGFi) are standard treatments for patients (pts) with mRCC. This phase I/II study evaluated the safety and efficacy of the novel combination of pembrolizumab (pembro) and cabozantinib (cabo). The phase I dose escalation data was presented at ASCO GU 2019. We now report the objective response rate (ORR), progression free survival (PFS), overall survival (OS), and toxicity of patients in the phase II dose expansion. Methods: Eligible pts had metastatic clear cell (ccRCC) or non-clear cell (nccRCC) histology, normal organ function, ECOG 0-1, and no prior exposure to pembro or cabo. Pts could be treatment-naïve or have received prior CPI and/or VEGFi. Pts were dosed at the recommended phase 2 dose of pembro 200 mg IV Q3W in combination with cabo 60 mg PO QD. Scans were obtained every 9 weeks. Treatment beyond progression, in the setting of continued clinical benefit, was allowed. The primary endpoint was ORR. Simon’s two-stage design was implemented to test the null hypothesis that ORR ≤ 0.20 versus the alternative that ORR ≥ 0.50. Results: Forty pts were enrolled, of which 34 pts (85%) had ccRCC and 6 pts (15%) had nccRCC. This was first-line treatment for 15 pts (38%) and second- and subsequent-line therapy for 25 pts (62%). IDMC risk category was favorable in 15%, intermediate in 72.5%, and poor in 12.5% of pts. Prior therapies included VEGFi in 17 pts (43%), CPI in 17 pts (43%), and 9 pts (23%) had both prior VEGFi and CPI in combination or sequentially. At a median follow up of 17.8 months (mo), the ORR was 60% (95% CI 0.458-1.00), clinical benefit rate (CBR) was 92.5% (95% CI 0.817-1.00), median time to response was 4.2 mo; median duration of response was 8.4 mo. Three of six nccRCC pts achieved partial response. Median PFS was 10.4 mo (95% CI 6.3 mo-NR). Median OS was not reached. Twelve patients remain on treatment. The most common grade 1 and 2 (G1/2) treatment-related AEs were diarrhea (53%), fatigue (49%), weight loss (47%), nausea (43%), and dysgeusia (43%). Twenty-five patients (47%) experienced a treatment-related G3 AE and there were no G4 related AEs. Thirteen pts experienced serious adverse events, 8 of which were related to treatment: G3 transaminitis and hypoglycemia were attributed to the combination; G3 pancreatitis, nephritis, and pneumonitis attributed to pembro; G3 pulmonary embolus, confusion due to reversible posterior leukoencephalopathy (RPLS), and stroke attributed to cabo. There was one treatment-related death in the pt with RPLS, possibly related to cabo. Conclusions: This study of the combination of pembrolizumab 200mg and cabozantinib 60mg met the primary endpoint of ORR. Benefit was seen in first- and subsequent-line therapy. The safety profile was manageable. This combination warrants further confirmation in a randomized controlled trial. Clinical trial information: NCT03149822.

Prostate cancer patients (pts) with non-metastatic prostate specific antigen (PSA) progression after local therapy and a long PSA doubling time (PSADT) usually have a period of PSA observation prior to starting on androgen deprivation therapy (ADT). We report results of an investigator-initiated, IRB-approved Phase II clinical trial (CT.gov-NCT03087903) investigating grape seed extract (GSE) in pts with PSA-only recurrence after maximum local therapy for prostate cancer. Pts with baseline PSA ≥ 0.2 ng/mL and rising PSA on 2 separate occasions and no evidence of metastases were eligible. Pts with baseline PSADT < 4 weeks (if absolute PSA > 2 ng/mL) were excluded. Pts were given 150mg of GSE orally twice daily for 12 months. GSE was administered as a formulation Leucoselect Phytosome-Indena S.p.A. (~100% proanthocyanidins, enriched in lower procyanidin oligomers complexed with soy phospholipids, about 1:2.6 w/w), with increased bioavailability. Study endpoints included PSA response (defined as an increase in PSADT by 30%) and change in PSA velocity. PSA was checked at baseline, 6 weeks and 3, 6, 9, and 12 months after starting GSE. Pts were removed from the trial with clinical/radiographic progression or if PSADT was less than 3 months. Pts completed dietary surveys and provided biologic specimens for tissue banking. The association of time and PSA level was assessed using a mixed effect modeling approach with the intention of calculating the doubling time. The natural log of PSA was taken to satisfy the linearity assumption of this method. Notably, pts on observation with a rising PSA after treatment for prostate cancer could be accrued rapidly to clinical trials; 27 pts were screened for this clinical trial at two sites (between January 2018 - August 2018) with 20 pts registered and started on treatment. Median (range) age and baseline PSA of pts enrolled were 71 (60 - 83) and 2.65 (0.44 - 17.44), respectively. Mean pretreatment PSADT was 5.4 months. GSE was well tolerated without serious adverse effects. 8 patients were withdrawn early due to PSADT progression of Citation Format: Paul Maroni, Elizabeth R. Kessler, Rodrigo Rodrigues-Pessoa, Andrew Nicklawsky, Thomas Flaig, Elaine Lam, Brandon Bernard, James Moore, Kyra Anderson, Dexiang Gao, Komal Raina, Rajesh Agarwal. A phase II trial using grape seed extract for prostate cancer patients with non-metastatic PSA progression after local therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT207.

e14007 Background: The medical oncology patient population is at high risk for adverse effects and complications related to anti-cancer treatments. The cost of oncology care is projected to reach almost $160 billion in 2020. The ongoing cost trajectory has placed a significant financial burden on patients, families, and society as a whole. The Centers for Medicare and Medicaid Service (CMS) has developed a new payment and delivery model that identifies potentially preventable conditions for ED visits/rehospitalizations among patients that are receiving anti-cancer therapies. Proposed CMS changes have created increased urgency around avoiding preventable ED visits/rehospitalizations. In response to the need for high quality, patient centered, cost effective care, we have established an APP-led acute care clinic that specializes in oncology care. Methods: The Clinical Assessment and Rapid Evaluation (CARE) Clinic offers acute care and symptom management catered to the oncology population. Patients are able to receive lab and imaging work up in addition to intervention with IV fluids, anti-emetics, opioids, electrolytes or antibiotics, as well as blood/platelets as warranted. To assess patient satisfaction, we created an anonymous four question survey delivered to CARE clinic patients over a two month period. Results: Seventy five surveys were collected. Pain and nausea were the leading reasons for encounters. 91% of patients rated their care as excellent, while 9% of patients rated their care as good. 33% of patients reported they would have been seen in the ED if the CARE Clinic was not available. Conclusions: The CARE Clinic represents a unique, one of the first of its kind, acute care and symptom management entity that utilizes an APP model to provide high quality care at a low cost. More research is needed to identify if this model can create statistically significant reduction in ED visits and rehospitalizations, however current data suggests that patients are highly satisfied with this unique method of care delivery. Sources Handley NR, Schuchter LM, Bekelman JE. Best Practices for Reducing Unplanned Acute Care for Patients With Cancer. Journal of Oncology Practice. 2018;14(5):306-313. doi:10.1200/jop.17.00081.

TPS5597 Background: Alterations in DNA damage repair genes are common in metastatic castration-resistant prostate cancer (mCRPC), and are implicated in responses to carboplatin, PARP inhibitors and immunotherapeutics. The ATR kinase is involved in the DNA damage response, and ATR inhibitors have been demonstrated in preclinical models to have synergistic activity with platinum compounds due to induction of replication stress. Methods: This is a randomized open-label Phase 2 study of the ATR inhibitor M6620 + carboplatin vs. docetaxel + carboplatin in mCRPC. Patients (pts) previously treated with at least one secondary hormonal therapy and taxane-based chemotherapy undergo mandatory pre-treatment biopsy and are randomized 1:1 to receive Arm A (docetaxel 60 mg/m2 day 1 + carboplatin AUC 4 day 1) or Arm B (M6620 90 mg/m2 days 2,9 + carboplatin AUC 5 day 1) every 21 days. Pts randomized to Arm A who are not candidates for docetaxel receive carboplatin AUC 5 monotherapy. Stratification factors are 1) prior PARP inhibitor (yes vs. no) and 2) evaluable disease by RECIST 1.1 (yes vs. no). Pts on Arm A crossover to Arm B (M6620+carboplatin) at the earlier of PSA or radiographic progression. For the primary endpoint of overall response rate (ORR; PSA reduction by ≥ 50% or radiographic response by RECIST 1.1), with 65 pts on each arm (total N = 130), there will be 80% power to distinguish ORR of 40% vs. 20% using a chi-square test (one sided α = 0.05). 136 pts will be enrolled to account for 5% dropout. Secondary endpoints include time to PSA progression, radiographic PFS, PFS by PCWG3 criteria, safety and adverse events in each arm. Biomarker studies include whole exome sequencing, RAD51 focus formation, and ATM IHC from tumor specimens. Circulating cell-free DNA from pre-treatment and progression plasma specimens will undergo ultra-low pass whole genome sequencing and deep targeted sequencing. The goal of this study is to expand therapeutic options in mCRPC through a novel approach to targeting the DNA damage response, and to identify biomarkers associating with response and resistance to both standard and trial therapy. Enrollment began June 2019 (NCI/ETCTN #10191, NCT03517969). Clinical trial information: NCT03517969 .