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Transgender individuals represent 0.55% of the US population, equivalent to 1.4 million transgender adults. In transgender women, feminisation can include a number of medical and surgical interventions. The main goal is to deprive the phenotypically masculine body of androgens and simultaneously provide oestrogen therapy for feminisation. In gender-confirming surgery (GCS) for transgender females, the prostate is usually not removed. Due to limitations of existing cohort studies, the true incidence of prostate cancer in transgender females is unknown but is thought to be less than the incidence among cis-gender males. It is unclear how prostate cancer develops in androgen-deprived conditions in these patients. Six out of eleven case reports in the literature presented with metastatic disease. It is thought that androgen receptor-mediated mechanisms or tumour-promoting effects of oestrogen may be responsible. Due to the low incidence of prostate cancer identified in transgender women, there is little evidence to drive specific screening recommendations in this patient subpopulation. The treatment of early and locally advanced prostate cancer in these patients warrants an individualised thoughtful approach with input from patients' reconstructive surgeons. Both surgical and radiation treatment for prostate cancer in these patients can profoundly impact the patient's quality of life. In this review, we discuss the evidence surrounding screening and treatment of prostate cancer in transgender women and consider the current gaps in our knowledge in providing evidence-based guidance at the molecular, genomic and epidemiological level, for clinical decision-making in the management of these patients.

PURPOSE Data quality and standardization remain a challenge when analyzing real-world clinical data. We built a clinical research database, using machine learning and natural learning processing, and investigated factors influencing testosterone recovery (T-recovery) in patients with localized prostate cancer (LPC) after initial androgen deprivation therapy (ADT). METHODS Medication and treatment-associated dates missing in structured tables were extracted from patient notes using ConceptMapper, an automated data extraction tool, standardized and curated in Sema4 clinical research database. ADT usage duration was evaluated, and T-recovery in patients with LPC was analyzed by the Kaplan-Meier method and multivariable Cox proportional hazards models. We assessed the prognostic value of post-ADT T-recovery with prostate-specific antigen progression-free survival and failure-free survival. RESULTS In total, 4,125 of 30,832 (13.4%) patients with prostate cancer had medication exclusively from notes with high precision and recall, F1 score ≥ 0.95. Association of dates with medication usage had a F1 score of 0.76. ADT duration estimation had higher accuracy combining information from notes to tables from electronic medical record (70% v 45%). Baseline testosterone was the strongest predictor of T-recovery in these patients. Patients with a baseline testosterone ≥ 300 ng/dL recovered in 9.79 versus 38 months for patients with baseline testosterone < 300 ng/dL ( P < .0001). Shorter prostate-specific antigen progression-free interval was observed for patients with T-recovery (≥ 300 ng/dL) at 6 months after ADT cessation compared with patients without T-recovery (< 300 ng/dL; 13.7 v 25.1 months; P = .055). CONCLUSION We augmented structured electronic medical record data with data extracted from notes and improved the accuracy of medication information for patients. ADT exposure and T-recovery in patients with LPC produced results consistent with the literature and clinical experience and illustrates the power of applying machine learning methods to enhance the quality of real-world evidence in answering clinically relevant questions.

Prostate-specific antigen (PSA) is a valuable prognostic and predictive biomarker in prostate cancer; however, the significance of PSA at or near the time of death is not well understood. This study aimed to characterize the significance of PSA at death in patients with metastatic castration-resistant prostate cancer (mCRPC).The Mount Sinai Genitourinary Cancer Biorepository, an institutional review board-approved, single-institution database containing all consented genitourinary cancer patients seen between 2010 and 2018, was used to identify and stratify patients into the following cohorts based on their PSA at or near death:100 ng/mL, 100-1000 ng/mL, and1000 ng/mL. Analyses were performed to assess clinical characteristics of disease, treatment response, and outcomes.We identified 1097 patients with prostate cancer, and 101 were confirmed to be deceased following a diagnosis of mCRPC. In patients with mCRPC, cohorts of higher PSA level at death were associated with lower Gleason score at diagnosis and a trend toward longer time to mCRPC and longer time from diagnosis to death, despite a higher burden of disease at death. Conversely, subgroup analysis of PSA10 ng/mL at death was associated with lower rates of imaging within 6 months of death, lower treatment rate, and worse clinical outcomes.Cohorts of different PSA levels at death in mCRPC patients showed distinct patterns of disease characteristics and clinical outcomes, likely due to the underlying molecular phenotype differences. Imaging for the patient population with very low PSA levels may be underutilized and should be considered more routinely.

Advance diagnostic and treatment modalities have improved outcomes for renal cell carcinoma (RCC) patients, but the prognosis for those with metastatic disease (mRCC) remains poor. As given metastatic distribution is critical in guiding treatment decisions for mRCC patients, we evaluated evolving metastatic patterns to assess if our current practice standards effectively address patient needs. A systematic literature review was performed to identify all publicly available prospective clinical trials in metastatic renal cell carcinoma (mRCC) from 1990 to 2018. A total of 16,899 mRCC patients from 127 qualified phase I–III clinical trials with metastatic site documentations were included for analysis for incidence of metastases to lung, liver, bone, and lymph nodes (LNs) over time. Studies were categorized into three treatment eras based on the timing of regulatory approval: Cytokine Era (1990-2004), vascular endothelial growth factor/tyrosine kinase inhibitor (TKI) Era (2005-2016), and immune checkpoint inhibitor/TKI Era (ICI-TKI, 2017-2018) and also classified as first-line only (FLO) or second-line and beyond (SLB). Overall, an increase in the incidence of bone and LNs metastases in FLO and SLB, and lung metastases in FLO, was seen over the three treatment eras. Generally, the burden of disease is higher in SLB when compared with FLO. Importantly, in the ICI-TKI era, the incidences of bone metastasis are 28% in FLO and 29% in SLB settings. The disease burden in patients with mRCC has increased steadily over the past three decades. Given the unexpectedly high rate of bone metastasis, routine dedicated bone imaging should be considered in all patients with mRCC.

BackgroundUntil recently there were no genome-directed therapies (GDTs) requiring next-generation sequencing (NGS) in prostate cancer. We examined whether the US approval of poly-(ADP-ribose) polymerase (PARP) inhibitors in May 2020 influenced the actionability and utilization of NGS in patients with prostate cancer.MethodsThis was a single-center, retrospective study including men with prostate cancer who received NGS testing from a single lab between 7/11/2018-7/6/2021. Clinical and testing data were derived from the electronic medical record.ResultsThere were 346 patients with prostate cancer and qualifying NGS testing during the study period. Overall, 55 patients (15.9%) had qualifying homologous recombination repair (HRR) alterations for PARP inhibitor treatment. A greater proportion of alterations were actionable post-approval compared to pre-approval (22.7% vs 0%, Chi-squared pConclusionIn this single-center cohort, the approval of PARP inhibitors for later-line treatment of metastatic prostate cancer increased the actionability of NGS findings but did not lead to earlier use of NGS testing.

Background In the phase III SPARC trial, satraplatin, an oral platinum analogue, demonstrated anticancer activity in men with metastatic castration-resistant prostate cancer (mCRPC). Repeat biopsies are uncommon in mCRPC, limiting the feasibility of tissue–based biomarkers. This phase II study sought to evaluate the feasibility and utility of blood–based biomarkers to identify platinum–sensitive mCRPC. Methods Patients with mCRPC who had progressed on docetaxel were enrolled at a single center from 2011 to 2013. Subjects received satraplatin 80 mg/m2 by mouth daily on days 1-5 and prednisone 5 mg PO twice daily, on a 35-day cycle. Serial peripheral blood samples were collected for biomarker assessment. Results Thirteen docetaxel-refractory mCRPC patients were enrolled, with a median age of 69 years (range 54-77 years) and median PSA of 71.7 ng/mL (range 0.04-3057). Four of 13 patients (31%) responded to satraplatin (defined as a PSA decline of ≥30%). Responders demonstrated improved time to disease progression (206 vs. 35 days, HR 0.26, 95% CI, 0.02-0.24, P = .003). A 6-gene peripheral blood RNA signature and serum tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were assessed as biomarkers, but neither was significantly associated with response to satraplatin. Conclusion In this small series, one-third of mCRPC patients responded to platinum–based chemotherapy. Peripheral blood biomarker measurement is feasible in mCRPC, though the biomarkers we investigated were not associated with platinum response. Other biomarkers, such as DNA damage repair mutations, should be evaluated.

Background The most common site of disease in metastatic castration‐resistant prostate cancer (mCRPC) is the bone. The ALSYMPCA study demonstrated that radium‐223 significantly improved overall survival (OS) in mCRPC patients with symptomatic bone metastases and without visceral metastases. However, administration requires a multidisciplinary approach and an infrastructure that supports coordination of care, which may differ by practice site. We aimed to evaluate practice patterns and treatment outcomes in patients with mCRPC treated at a community practice (CP) compared with those treated at an academic center (AC). Methods This retrospective review included 200 adult mCRPC patients receiving radium‐223 between January 2014 and June 2017. The primary endpoint, OS, was estimated from the date of radium‐223 initiation. Secondary outcomes included a comparison of baseline characteristics, reasons for initiation and discontinuation of radium‐223, and treatment sequencing. A subset analysis of OS based on the number of radium‐223 doses and on sequencing of radium‐223 either before or after chemotherapy was also conducted. Results Most patients were treated at a CP (57%). Patients treated at CP sites were significantly older (74.9 vs. 71.9 years; p = .031) and had more comorbidities (Klabunde score 1.1 vs. 0.7; p = .020) than those in an AC but initiated treatment within a shorter period of time from diagnosis of mCRPC (1.3 vs. 1.9 years; p

Purpose: Stress-induced adrenergic signaling can suppress the immune system. In animal models, pharmacological beta-blockade stimulates CD8+ T-cell activity and improves clinical activity of immune checkpoint blockade (ICB) in inhibiting tumor growth. Herein, we investigated the effect of BB on clinical outcomes of patients receiving ICB in advanced solid tumors.Methods:We retrospectively evaluated patients with solid tumors treated with ICB at our institution from January 1, 2011 to April 28, 2017. The primary clinical outcome was disease control. Secondary clinical outcomes were overall survival (OS), and duration of therapy (DoT). The primary predictor was use of BB. Association between disease control status and BB use was assessed in univariable and multivariable logistic regression. OS was calculated using hazard ratios of BB-recipient patients versus BB non-recipient patients via Cox proportional hazards regression models. All tests were two-sided at a significance level of 0.05. ResultsOf 339 identified patients receiving ICB, 109 (32%) also received BB. In covariate-adjusted analysis, odds of disease control were significantly higher among BB recipients compared to BB-non-recipients (2.79; [1.54-5.03]; p=0.001). While we did not observe significant association of OS with the use of BB overall, significant association with better OS was observed for the urothelial carcinoma cohort (HR: 0.24; [0.09, 0.62]; P=0.0031). Conclusions:Concurrent use of BB may enhance the clinical activity of ICB and influence overall survival, particularly in patients with urothelial carcinoma. Our findings warrant further investigation to understand the interaction of beta adrenergic signaling and antitumor immune activity and explore a combination strategy.

Background Systemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow-growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature. Methods This was a prospective observational study of patients with mRCC across 46 US community and academic centers. The objective was to describe baseline characteristics and demographics of patients with mRCC initially managed by AS, reasons for AS, and patient outcomes. Descriptive statistics were used to characterize demographics, baseline characteristics, and patient-related outcomes. Wilcoxon 2-sample rank-sum tests and χ2 tests were used to assess differences between ST and AS cohorts in continuous and categorical variables, respectively. Kaplan-Meier survival curves were used to assess survival. Results Of 504 patients, mRCC was initially managed by AS (n = 143) or ST (n = 305); 56 patients were excluded from the analysis. Disease was present in 69% of patients who received AS, whereas the remaining 31% had no evidence of disease. At data cutoff, 72 of 143 patients (50%) in the AS cohort had not received ST. The median overall survival was not reached (95% CI, 122 months to not estimable) in patients who received AS versus 30 months (95% CI, 25-44 months) in those who received ST. Quality of life at baseline was significantly better in patients who were managed with AS versus ST. Conclusions AS occurs frequently (32%) in real-world clinical practice and appears to be a safe and appropriate alternative to immediate ST in selected patients.

Docetaxel is widely used in metastatic castration-resistant prostate cancer (mCRPC), however its optimal use remains unclear in the current treatment landscape. Biomarkers to predict Docetaxel toxicity may help optimize treatment selection. We aimed to create a predictive model for toxicity-related Docetaxel discontinuation (TRDD). Through Project Data Sphere, we accessed individual patient data from the control arms of three frontline mCRPC trials: ASCENT2, VENICE, and MAINSAIL. The inclusion criteria for these trials were all similar and included patients with chemotherapy-naive mCRPC. The primary outcome was occurrence of TRDD. A competing risks regression (CRR) was used to predict TRDD, after accounting for the occurrence of competing events (death or progression). The output of the model was used as the dependent variable on a classification and regression tree (CART) to identify risk groups for TRDD. Overall, 1568 patients were considered. Pooled CI of TRDD was 19% after accounting for competing events (death: 474; progression: 59) within 12 months of starting treatment. To build a risk calculator we relied on a CRR that ultimately included age, ECOG performance status, AST, bilirubin, use of analgesics, and presence of diabetes and chronic kidney disease. The CART analysis identified three risk groups that were named: low (model-derived TRDD risk ≤24%), intermediate (25–64%), and high (≥65%) risk group. In each risk group, probability of TRDD during treatment was 14%, 58%, and 79%, and median OS was 24 months, 20 months, and 13 months, respectively (p

Objectives Immune checkpoint inhibitors (ICIs) are being increasingly used across cancer types. Emergency room (ER) and inpatient (IP) care, common in patients with cancer, remain poorly defined in this specific population, and risk factors for such care are unknown. Methods We retrospectively reviewed charts for patients with solid tumors who received >1 ICI dose at 1 of 2 sites from January 1, 2011 to April 28, 2017. Demographics, medical history, cancer diagnosis/therapy/toxicity details, and outcomes were recorded. Descriptive data detailing ER/IP care at the 2 associated hospitals during ICI therapy (from first dose to 3 mo after last dose) were collected. The Fisher exact test and multivariate regression analysis was used to study differences between patients with versus without ER/IP care during ICI treatment. Results Among 345 patients studied, 50% had at least 1 ER visit during ICI treatment and 43% had at least 1 IP admission. Six percent of ER/IP visits eventually required intensive care. A total of 12% of ER/IP visits were associated with suspected or confirmed immune-related adverse events. Predictors of ER care were African-American race (odds ratio [OR]: 3.83, P=0.001), Hispanic ethnicity (OR: 3.12, P=0.007), and coronary artery disease (OR: 2.43, P=0.006). Predictors of IP care were African-American race (OR: 2.38, P=0.024), Hispanic ethnicity (OR: 2.29, P=0.045), chronic kidney disease (OR: 3.89, P=0.006), angiotensin converting enzyme inhibitor/angiotensin receptor blocker medication use (OR: 0.44, P=0.009), and liver metastasis (OR: 2.32, P=0.003). Conclusions Understanding demographic and clinical risk factors for ER/IP care among patients on ICIs can help highlight disparities, prospectively identify high-risk patients, and inform preventive programs aimed at reducing such care.

Background Early cancer detection could identify tumors at a time when outcomes are superior and treatment is less morbid. This prospective case-control sub-study (from NCT02889978 and NCT03085888) assessed the performance of targeted methylation analysis of circulating cell-free DNA (cfDNA) to detect and localize multiple cancer types across all stages at high specificity. Participants and methods The 6689 participants [2482 cancer (>50 cancer types), 4207 non-cancer] were divided into training and validation sets. Plasma cfDNA underwent bisulfite sequencing targeting a panel of >100 000 informative methylation regions. A classifier was developed and validated for cancer detection and tissue of origin (TOO) localization. Results Performance was consistent in training and validation sets. In validation, specificity was 99.3% [95% confidence interval (CI): 98.3% to 99.8%; 0.7% false-positive rate (FPR)]. Stage I–III sensitivity was 67.3% (CI: 60.7% to 73.3%) in a pre-specified set of 12 cancer types (anus, bladder, colon/rectum, esophagus, head and neck, liver/bile-duct, lung, lymphoma, ovary, pancreas, plasma cell neoplasm, stomach), which account for ∼63% of US cancer deaths annually, and was 43.9% (CI: 39.4% to 48.5%) in all cancer types. Detection increased with increasing stage: in the pre-specified cancer types sensitivity was 39% (CI: 27% to 52%) in stage I, 69% (CI: 56% to 80%) in stage II, 83% (CI: 75% to 90%) in stage III, and 92% (CI: 86% to 96%) in stage IV. In all cancer types sensitivity was 18% (CI: 13% to 25%) in stage I, 43% (CI: 35% to 51%) in stage II, 81% (CI: 73% to 87%) in stage III, and 93% (CI: 87% to 96%) in stage IV. TOO was predicted in 96% of samples with cancer-like signal; of those, the TOO localization was accurate in 93%. Conclusions cfDNA sequencing leveraging informative methylation patterns detected more than 50 cancer types across stages. Considering the potential value of early detection in deadly malignancies, further evaluation of this test is justified in prospective population-level studies.

Bacteriochlorins are crucial to photosynthesis in bacteria. Studies of air-stable, meso-substituted bacteriochlorins are rare. We herein report the synthesis, properties, and photovoltaic performance of three new air-stable, meso-substituted bacteriochlorins bearing a dioctylfluorenylethyne (denoted as LS-17), a dioctylaminophenylethynylanthrylethyne (LS-43), and a diarylaminoanthrylethyne (LS-45) as the electron-donating groups. Among these LS-bacteriochlorins, LS-17 displays sharp UV-visible absorption bands whereas LS-43 and LS-45 give rise to broadened and red-shifted absorptions. Electrochemical and DFT results suggest that the first oxidation and reduction reactions of these bacteriochlorins are consistent with the formation of the cation and anion radicals, respectively. For dye-sensitized solar cell applications, photovoltaic performance of the LS-45 cell achieves an overall efficiency of 6.04% under one-sun irradiation.

Immunotherapy has revolutionized the treatment landscape for many cancer types. The treatment for renal cell carcinoma (RCC) has especially evolved in recent years, from cytokine-based immunotherapies to immune checkpoint inhibitors. Although clinical benefit from immunotherapy is limited to a subset of patients, many combination-based approaches have led to improved outcomes. The success of such approaches is a direct result of the tumor immunology knowledge accrued regarding the RCC microenvironment, which, while highly immunogenic, demonstrates many unique characteristics. Ongoing translational work has elucidated some of the mechanisms of response, as well as primary and secondary resistance, to immunotherapy. Here, we provide a comprehensive review of the RCC immunophenotype with a specific focus on how preclinical and clinical data are shaping the future of immunotherapy.

INTRODUCTIONAND OBJECTIVE: Docetaxel is widely used in metastatic castration-resistant prostate cancer (mCRPC), however its optimal use remains unclear. Biomarkers and prediction models assessing e...

e16520 Background: Adrenergic receptors (ADR) have a well-established role in kidney physiology, suggesting a possible role of ADR signaling in renal cell carcinoma (RCC). Preclinical studies have shown a possible anti-tumor effect of both alpha-adrenergic blockers (AB) and beta-adrenergic blockers (BB) on renal cancer cells. However, the literature is conflicting regarding the effect on clinical outcomes. In addition, there is no comprehensive analysis of what role these medications have specifically in RCC patients with metastatic disease. In this single health system retrospective study, we evaluate the effect of AB or BB prescription on cancer-specific outcomes in patients with metastatic RCC. Methods: Clinical data was abstracted from the electronic health record and the institutional cancer registry at The Mount Sinai Health System to include patients with RCC diagnosed with metastatic disease ( de novo or relapsed) between 2016-2020. Follow up data was recorded until a data lock of 4/1/2021. Multivariate Cox regression was used to evaluate the association of AB and BB prescription on overall survival (OS) for the entire cohort and progression free survival (PFS) for patients who received any first line therapy. Multivariate logistic regression was used to evaluate association of these medications with overall response rate (ORR) of first line therapies with available data on initial response. Analyses were controlled for clinical risk factors including age at diagnosis, sex, race, treatment plan including immunotherapy, and medical history of benign prostatic hyperplasia, hypertension, or heart failure. Data was analyzed using R version 4.1.0. Results: 133 patients were identified for inclusion in the study. 61% of cases are de novo metastatic and 39% are relapsed from previously resected disease. 71% are clear cell histology, 3.8 % are papillary, and the rest are unspecified/other. 84 patients (63%) received at least a 1st line systemic therapy. AB or BB prescription alone is not associated with OS, PFS, or ORR. However, prescription of both AB and BB is associated with worse OS (HR 2.94 95% CI 1.13-7.68), worse PFS (HR 7.70 95% CI 1.80-33.0), and decreased odds of responding to 1st line therapy (OR 0.06 95% CI 0.00-0.55) on multivariate analysis. Conclusions: The data suggests that the concurrent use of both an AB and BB in patients with metastatic RCC leads to worse clinical outcomes. What remains unclear is if there is a negative synergistic effect of these medications on RCC pathophysiology or if the prescription of these medications is associated with another negative confounding clinical factor. Since these medications are commonly utilized for cardiovascular disease, multivariate analyses attempted to control for these comorbidities. Future studies may add to this data by cataloging the severity of heart failure and doses of AB and BB medications used in a RCC cohort.

To test whether body mass index (BMI) amongst patients with metastatic castration-resistant prostate cancer (mCRPC) is associated with overall survival (OS) and cancer-specific survival.Individual patient data from 1577 men with mCRPC treated with docetaxel and prednisone from the control arms of ASCENT2, VENICE, and MAINSAIL were considered. The role of BMI on survival outcomes was investigated both as a continuous and categorical variable (≤24.9 vs. 25-29.9 vs. ≥30 km/mThe median (IQR) age for the patient population was 69 (63,74) years with a median (IQR) BMI of 28 (25-31) kg/mObese patients with mCRPC had better cancer-specific and overall survival as compared to overweight and normal weight patients. The protective effect of BMI was not related to receiving higher chemotherapy doses. Further studies aimed at elucidating the biological mechanism behind this effect are warranted.

Objective: To test whether body mass index (BMI) amongst patients with metastatic castration-resistant prostate cancer (mCRPC) is associated with overall survival (OS) and cancer-specific survival. Methods: Individual patient data from 1577 men with mCRPC treated with docetaxel and prednisone from the control arms of ASCENT2, VENICE, and MAINSAIL were considered. The role of BMI on survival outcomes was investigated both as a continuous and categorical variable (≤24.9 vs. 25–29.9 vs. ≥30 km/m2). BMI ≥ 30 kg/m2 was considered obese. Analyses were adjusted for age, PSA, ECOG performance status, number of metastases and prior treatment. The Cox semi-proportional hazard model was used to predict OS, whereas competing risks regression was used for predicting cancer-specific mortality (CSM). To exclude any possible effect attributable to higher doses of chemotherapy (titrated according to body-surface area), we checked for eventual interactions between BMI and chemotherapy dose (both as continuous-continuous and categorical-continuous interactions). Results: The median (IQR) age for the patient population was 69 (63,74) years with a median (IQR) BMI of 28 (25–31) kg/m2. Median follow-up for survivors was 12 months. Of the 1577 patients included, 655 were deceased by the end of the studies. Regarding OS, BMI emerged as a protective factor both as a continuous variable (HR: 0.96; 95% CI: 0.94, 0.99; p = 0.015) and as a categorical variable (obesity: HR: 0.71, 95% CI: 0.53, 0.96; p = 0.027, relatively to normal weight). The protective effect of high BMI on CSM was confirmed both as a continuous (SHR: 0.94; 95% CI: 0.91, 0.98; p = 0.002) and as a categorical variable (obesity SHR: 0.65; 95% CI: 0.45, 0.93; p = 0.018). No interaction was detected between the BMI categories and the docetaxel dose at any level in our analyses (all p » 0.05). Conclusions: Obese patients with mCRPC had better cancer-specific and overall survival as compared to overweight and normal weight patients. The protective effect of BMI was not related to receiving higher chemotherapy doses. Further studies aimed at elucidating the biological mechanism behind this effect are warranted.

Introduction : The Metastatic Renal Cell Carcinoma (MaRCC) Registry provides prospective data on real-world treatment patterns and outcomes in patients with metastatic renal cell carcinoma (mRCC). Methods and Materials : Patients with mRCC and no prior systemic therapy were enrolled at academic and community sites. End of study data collection was in March 2019. Outcomes included overall survival (OS). A survey of treating physicians assessed reasons for treatment initiations and discontinuations. Results : Overall, 376 patients with mRCC initiated first-line therapy; 171 (45.5%) received pazopanib, 75 (19.9%) sunitinib, and 74 (19.7%) participated in a clinical trial. Median (95% confidence interval) OS was longest in the clinical trial group (50.3 [35.8–not reached] months) versus pazopanib (39.0 [29.7–50.9] months) and sunitinib 26.2 [19.9–61.5] months). Non-clear cell RCC (21.5% of patients) was associated with worse median OS than clear cell RCC (18.0 vs 47.3 months). Differences in baseline characteristics, treatment starting dose, and relative dose exposure among treatment groups suggest selection bias. Survey results revealed a de-emphasis on quality of life, toxicity, and patient preference compared with efficacy in treatment selection. Conclusion : The MaRCC Registry gives insights into real-world first-line treatment selection, outcomes, and physician rationale regarding initial treatment selection prior to the immunotherapy era. Differences in outcomes between clinical trial and off-study patients reflect the difficulty in translating trial results to real-world patients, and emphasize the need to broaden clinical trial eligibility. Physician emphasis on efficacy over quality of life and toxicity suggests more data and education are needed regarding these endpoints. MicroAbstract : The Metastatic Renal Cell Carcinoma Registry provides prospective data on real-world treatment patterns and outcomes in patients with metastatic renal cell carcinoma (mRCC). 376 patients with mRCC and no prior systemic therapy were included in this study. This report describes initial real-world treatment patterns. Physician emphasis on efficacy over quality of life and toxicity suggests more data and education are needed.

Introduction: Although pharmacist-driven patient education has been shown to increase adherence, reduce medication errors, and lower 30-day readmission rates, the data in the ambulatory oncology setting is limited. This pilot quality initiative study was conducted from June 1, 2018, to November 15, 2018, in the ambulatory cancer center affiliated with The Mount Sinai Hospital in New York, NY, to determine the impact of pharmacist counseling on chemotherapy regimens. Methods and Materials: English-speaking patients with gastrointestinal malignancies who were newly started on chemotherapy were selected for this study. They received a pharmacist-led education session regarding their medications, potential side effects, and how to manage them at home. After each session, they completed a 5-question survey on a 5-point Likert-scale about how they felt before and after speaking with a pharmacist. Survey results were analyzed by median scores and Wilcoxon signed-rank test. Results: Of the 96 patients who were counseled, 71 patients were included in this analysis. The median score increased from 3 to 5 for the understanding of their chemotherapy regimen and side effects (questions 1 and 2), 3 to 4.5 for knowledge about interactions with their oral chemotherapy (question 3), 4 to 5 for overall experience in the cancer center (question 5). The median score for anxiety level was unchanged at 3 (question 4). Conclusion: This survey-based study demonstrated the benefit of a pharmacist-led counseling session. An interdisciplinary approach involving the integration of oncology pharmacists in patient education can greatly impact the quality of care for oncology patients.

112 Background: Next-generation sequencing (NGS) is increasingly common in clinical practice, but its clinical utility may depend on the availability of sequencing-directed therapies (SDT). There were no FDA-approved SDTs in prostate cancer (PCa) until 2020, when PARP inhibitors olaparib and rucaparib were approved for tumors bearing alterations in certain homologous recombination repair (HRR) genes. We assessed the clinical utility of NGS in PCa before and after the approval of these agents in a single academic medical center. Methods: This was a retrospective single-center study including all PCa patients seen at Mount Sinai Hospital (New York, NY) between 2018–2021 who received NGS via the 161-gene Sema4 Signal Solid Tumor Panel. Clinical data were extracted from the Mount Sinai electronic medical record using a proprietary automated pipeline with limited manual curation (Sema4 PRODB). The primary outcome was clinical utility in metastatic PCa, defined as the proportion of metastatic PCa patients who received SDT. Secondary outcomes included time-to-next-treatment (TTNT, defined as time from SDT start to the start of next systemic therapy) and the proportion of patients with clinically actionable (as of 9/2021) alterations, defined as either Tier 1 (associated with FDA-approved treatments in prostate cancer) or Tier 2 (associated with either off-label or investigational agents). Results: The cohort consisted of 332 PCa patients; 51% (N = 170) were sequenced in 2020 or later. The median age at diagnosis was 65 (IQR 12). The most advanced stage documented was localized for 39% (N = 129) and metastatic for 61% (N = 203). Overall, 167 actionable alterations were identified in 125 patients (38% of cohort). Of the actionable alterations, 31% (N = 51) were Tier 1 and 69% (N = 116) were Tier 2. Of the 44 patients with Tier 1 alterations, 8 (18%) received SDT (all received olaparib). The proportion of metastatic patients receiving olaparib increased from 1% (2/145) before 2020 to 10% (6/58) during or after 2020 (p = 0.008). Of the 36 patients not receiving olaparib: 20 were sequenced before FDA approval and were treated with an alternative systemic therapy; 8 had localized disease and were not eligible; 8 had limited follow-up or unknown treatment status. For those who received olaparib, median TTNT was 5 months. Conclusions: In this single-center retrospective cohort, clinical utility of NGS was linked to treatment landscape. Increases in NGS test volume and olaparib use coincided with the approval of PARP inhibitors for patients with HRR-mutated prostate cancers. Notably, NGS was used to match patients to off-label/ investigational olaparib before its FDA approval.[Table: see text]

Background Cell entry of SARS-CoV-2 depends on binding of the viral spike (S) proteins to ACE2 and on S protein priming by TMPRSS2. Inhibition of TMPRSS2 may work to block or decrease the severity of SARS-CoV-2 infections. Intriguingly, TMPRSS2 is an androgen-regulated gene that is upregulated in prostate cancer where it supports tumor progression and is involved in a frequent genetic translocation with the ERG gene. First- or second-generation androgen-deprivation therapies (ADTs) decrease the levels of TMPRSS2. Here we put forward the hypothesis that ADTs may protect patients affected by prostate cancer from SARS-CoV-2 infections. Materials and methods We extracted data regarding 9280 patients (4532 males) with laboratory-confirmed SARS-CoV-2 infection from 68 hospitals in Veneto, one of the Italian regions that was most affected by the COVID-19 pandemic. The parameters used for each COVID-19 positive patient were gender, hospitalization, admission to intensive care unit (ICU), death, tumor diagnosis, prostate cancer diagnosis, and androgen-deprivation therapy (ADT). Results There were 9280 SARS-CoV-2 positive patients in the Veneto on April 1, 2020. Overall, males developed more severe complications, were more frequently hospitalized, and had a worse clinical outcome than females. Considering only the Veneto male population (2.4 Million men), 0.2% and 0.3% of non-cancer and cancer patients, respectively, tested positive for SARS-CoV-2. Comparing the total number of SARS-CoV-2 positive cases, prostate cancer patients receiving ADT had a significantly lower risk of SARS-CoV-2 infection compared to patients who did not receive ADT (OR 4.05; 95% CI 1.55-10.59). A greater difference was found comparing prostate cancer patients receiving ADT to patients with any other type of cancer (OR 5.17; 95% CI 2.02-13.40). Conclusion Our data suggest that cancer patients have an increased risk of SARS-CoV-2 infections than non-cancer patients. However, prostate cancer patients receiving ADT appear to be partially protected from SARS-CoV-2 infections., HIGHLIGHTS • SARS-CoV-2 infected men have a worse clinical outcome than women • Cancer patients have an increased risk of SARS-CoV-2 infection • Prostate cancer patients receiving androgen-deprivation therapies appear to be partially protected from the infection

Docetaxel is widely used in metastatic castration-resistant prostate cancer (mCRPC), however its optimal use remains unclear in the current treatment landscape. Biomarkers to predict Docetaxel toxicity may help optimize treatment selection. We aimed to create a predictive model for toxicity-related Docetaxel discontinuation (TRDD).Through Project Data Sphere, we accessed individual patient data from the control arms of three frontline mCRPC trials: ASCENT2, VENICE, and MAINSAIL. The inclusion criteria for these trials were all similar and included patients with chemotherapy-naïve mCRPC. The primary outcome was occurrence of TRDD. A competing risks regression (CRR) was used to predict TRDD, after accounting for the occurrence of competing events (death or progression). The output of the model was used as the dependent variable on a classification and regression tree (CART) to identify risk groups for TRDD.Overall, 1568 patients were considered. Pooled CI of TRDD was 19% after accounting for competing events (death: 474; progression: 59) within 12 months of starting treatment. To build a risk calculator we relied on a CRR that ultimately included age, ECOG performance status, AST, bilirubin, use of analgesics, and presence of diabetes and chronic kidney disease. The CART analysis identified three risk groups that were named: low (model-derived TRDD risk ≤24%), intermediate (25-64%), and high (≥65%) risk group. In each risk group, probability of TRDD during treatment was 14%, 58%, and 79%, and median OS was 24 months, 20 months, and 13 months, respectively (p 0.001).Treatment selection in mCRPC remains a challenge. Our model can help clinicians balance Docetaxel toxicity and efficacy. The three risk categories that we identified correlated with OS and this is particularly useful for an optimal shared decision-making process.

INTRODUCTION AND OBJECTIVE:Docetaxel is a widely used treatment option in metastatic castration-resistant prostate cancer (mCRPC). However, its optimal use remains unclear in the current treatment ...

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Purpose Level 1 evidence supports the use of neoadjuvant chemotherapy (NAC) for the treatment of muscle-invasive bladder cancer (MIBC), but observational data demonstrate that this approach is underused. A barrier to shared decision making is difficulty in predicting and communicating survival estimates after cystectomy with or without NAC. Methods We included patients with MIBC from the National Cancer Database treated with cystectomy. A state-transition model was constructed for calculating 5-year death risk using baseline patient-, tumor-, and facility-level variables. Internal-external cross-validation by geographic region was performed. The effect of NAC was integrated using a literature-derived hazard ratio. Bladder cancer–specific and other-cause mortality was estimated from all-cause mortality rates from US life tables. From the state-transition model, a Web-based tool was developed and pilot usability testing performed. Results A total of 9,824 patients with MIBC who underwent cystectomy were eligible for inclusion. Median overall survival was 39.6 months (95% CI, 37.4 to 42.4 months). Increasing age, higher clinical T stage, higher comorbidity index, and black race were associated with shorter survival. Private insurance, higher income, and cystectomy at a high-volume facility were associated with longer survival. The prediction model was well calibrated across geographic regions, with observed-to-predicted 5-year death risks ranging from 0.85 to 1.17. Absolute risk reductions with NAC varied from 8.6% to 10.1%. The Web-based tool allowed input of the predictor variables and a user-defined hazard ratio associated with the effect of NAC to generate individualized survival estimates. The tool demonstrated good usability with clinicians. Conclusion A Web-based tool was developed to individualize outcome prediction and communication in patients with MIBC treated with cystectomy with or without NAC to facilitate shared decision making.

// David J. Paulucci 1 , John P. Sfakianos 1 , Anders J. Skanderup 2 , Kathleen Kan 1 , Che-Kai Tsao 3 , Matthew D. Galsky 3 , A. Ari Hakimi 4 , Ketan K. Badani 1 1 Department of Urology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA 2 Computational Biology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA 3 Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA 4 Department of Surgery—Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA Correspondence to: Ketan K. Badani, email: Ketan.Badani@mountsinai.org Keywords: papillary renal cell carcinoma, racial disparities, immune system signaling, targeted therapy, immune response Received: May 03, 2016 Accepted: November 22, 2016 Published: December 23, 2016 ABSTRACT Significant disparities in survival, incidence and possibly response to current therapies exist between black and white patients with renal cell carcinoma (RCC). Recent genomic evidence to account for these disparities has been reported for clear cell RCC. However, racial disparities at the genomic level for papillary RCC (pRCC) which is a genetically distinct and less responsive histologic subtype of RCC have not been reported. Using The Cancer Genome Atlas (TCGA) data, the present study assessed gene-level expression, somatic mutation and pathway differences between 58 black and 58 white patients with pRCC propensity matched on age, gender and pathologic T stage. Distinct tumor biology with differential expression patterns were observed in black vs. white patients with pRCC. Specifically, significance analysis of microarrays was applied to TCGA gene expression data and identified 163 genes and 120 genes overexpressed in black and white patients, respectively (FDR q

Purpose Clinical trials are critical to informing cancer care but often are hampered by slow accrual and lack of generalizability because of poor geographic accessibility. We tested the feasibility of replacing onsite study visits with telemedicine visits in a prospective clinical trial. Methods Castration-naïve patients with prostate cancer and a rising serum prostate-specific antigen after definitive local therapy were eligible. Patients were required to have a single onsite visit for enrollment. Study treatment consisted of oral metformin 850 mg daily for 1 month followed by 850 mg twice daily for 5 months. Telehealth video visits (televisits) were conducted monthly by using a Health Insurance Portability and Accountability Act–compliant smartphone application. The primary objective was to determine the feasibility of telemedicine-enabled study visits. Secondary objectives were defining safety, anticancer activity, quality of life, and patient satisfaction. Results Fifteen patients with a median age of 68 years (range, 57 to 83 years) and median one-way driving time to the study center of 71 minutes (range, 12 to 147 minutes) were enrolled. The patients completed 84 eligible televisits (completion rate, 100%; 95% CI, 0.80 to 1). Diarrhea was the most common adverse event but was limited to grade 1 in severity; a single patient experienced grade ≥ 3 adverse events. Seven patients (46.7%; 95% CI, 24.8% to 69.9%) had a ≤ 20% increase in prostate-specific antigen relative to baseline. Patients agreed or strongly agreed that they would participate in a telemedicine-enabled clinical trial in the future. Conclusion To our knowledge, this interventional oncology clinical trial is the first to be conducted through telemedicine. Telemedicine-enabled trials are feasible and may overcome geographic barriers to trial participation. Metformin was generally well tolerated but associated with modest anticancer activity.

Purpose Given that randomized trials exploring adjuvant chemotherapy for bladder cancer have been underpowered and/or terminated prematurely, yielding inconsistent results and creating an evidence gap, we sought to compare the effectiveness of cystectomy versus cystectomy plus adjuvant chemotherapy in real-world patients. Patients and Methods We conducted an observational study to compare the effectiveness of adjuvant chemotherapy versus observation postcystectomy in patients with pathologic T3-4 and/or pathologic node-positive bladder cancer using the National Cancer Data Base. We compared overall survival using propensity score (–adjusted, –stratified, –weighted, and –matched) analyses based on patient-, facility-, and tumor-level characteristics. A sensitivity analysis was performed to examine the impact of performance status. Results A total of 5,653 patients met study inclusion criteria; 23% received adjuvant chemotherapy postcystectomy. Chemotherapy-treated patients were younger and more likely to have private insurance, live in areas with a higher median income and higher percentage of high school–educated residents, and have lymph node involvement and positive surgical margins (P < .05 for all comparisons). Stratified analyses adjusted for propensity score demonstrated an improvement in overall survival with adjuvant chemotherapy (hazard ratio, 0.70; 95% CI, 0.64 to 0.76), and similar results were achieved with propensity score matching and weighting. The association between adjuvant chemotherapy and improved survival was consistent in subset analyses and was robust to the effects of poor performance status. Conclusion In this observational study, adjuvant chemotherapy was associated with improved survival in patients with locally advanced bladder cancer. Although neoadjuvant chemotherapy remains the preferred approach based on level I evidence, these data lend further support for the use of adjuvant chemotherapy in patients with locally advanced bladder cancer postcystectomy who did not receive chemotherapy preoperatively.

Renal cancer ranks twelfth in incidence among cancers worldwide. Despite improving outcomes due to better therapeutic options and strategies, prognosis for those with metastatic disease remains poor. Current systemic therapeutic approaches include inhibiting pathways of angiogenesis, immune checkpoint blockade, and mTOR inhibition, but inevitably resistance develops for those with metastatic disease, and novel treatment strategies are urgently needed. Emerging molecular and epidemiological evidence suggests that quinazoline-based α1-adrenoceptor-antagonists may have both chemopreventive and direct therapeutic actions in the treatment of urological cancers, including renal cancer. In human renal cancer cell models, quinazoline-based α1-adrenoceptor antagonists were shown to significantly reduce the invasion and metastatic potential of renal tumors by targeting focal adhesion survival signaling to induce anoikis. Mechanistically these drugs overcome anoikis resistance in tumor cells by targeting cell survival regulators AKT and FAK, disrupting integrin adhesion (α5β1 and α2β1) and engaging extracellular matrix (ECM)-associated tumor suppressors. In this review, we discuss the current evidence for the use of quinazoline-based α1-adrenoceptor antagonists as novel therapies for renal cell carcinoma (RCC) and highlight their potential therapeutic action through overcoming anoikis resistance of tumor epithelial and endothelial cells in metastatic RCC. These findings provide a platform for future studies that will retrospectively and prospectively test repurposing of quinazoline-based α1-adrenoceptor-antagonists for the treatment of advanced RCC and the prevention of metastasis in neoadjuvant, adjuvant, salvage and metastatic settings.

e15109 Background: Regulatory T cells play a key role in protecting kidney cells from ischemic injury. Immune checkpoint inhibitors (ICIs) may increase the risk of acute kidney injury via inhibition of regulatory T cells [1, 2]. Prospective clinical trials have largely excluded patients with chronic kidney disease (CKD); thus, we have limited knowledge of the safety and efficacy of ICI in these patients. Herein, we hypothesize that patients with CKD receiving ICIs have worse clinical outcomes. Methods: This single-institution retrospective cohort study included adult patients with solid tumors who were treated with ICIs at The Mount Sinai Hospital between 2011 and 2017. Clinical endpoints [response to treatment, progression of disease (POD) on treatment, mortality] were compared between patients with and without CKD using multivariate logistic regression. Odds ratios were controlled for demographics, primary tumor type, presence of cardiovascular comorbidities, smoking status, incidence of renal adverse events, and a composite of stage of illness with indication for treatment [localized—neoadjuvant, localized—adjuvant, regionally advanced, metastatic disease]. Data were analyzed using R version 3.5.1 with the following packages: readr, dplyr, broom, lubridate, tableone. Results: 420 patients met inclusion criteria: 399 patients without CKD and 21 patients with CKD. Cohorts are well matched for demographics, smoking status, stage/indication for treatment. The CKD cohort has a higher proportion of patients with urothelial cancer compared to patients without CKD (33% vs 11%) as well as a higher proportion of patients with HTN (81% vs 53%), HF (14% vs 3%), and DM (48% vs 21%). There was no statistical difference in odds of response to treatment [OR 0.76, 95% CI 0.26-2.23], POD [OR 0.42, 95% CI 0.15-1.17], or mortality [OR 2.05, 95% CI 0.71-5.96] between the CKD and non-CKD cohort. Conclusions: The data suggest the presence of CKD is not associated with worse clinical outcomes in cancer patients treated with ICIs. As a small retrospective study, the conclusions are hypothesis-generating but support continued use of immunotherapy in CKD in clinical practice and the inclusion of patients with CKD in immunotherapy clinical trials to further clarify safety and efficacy. [Table: see text]

e15157 Background: Immune checkpoint inhibitors (ICIs) are widely adopted for multiple indications across various malignancies. Despite the surge in their use, what occurs at radiographic progression (rPOD) remains poorly characterized. Herein, we describe patients at our institution that experienced rPOD on ICIs. Methods: We retrospectively reviewed charts of patients (pts) with solid tumors that received at least 2 doses of ICI at our institution from 12/01/2010 to 04/25/2017. Patients’ demographic data, medical history, ICI course, and outcomes were recorded. Characteristics at rPOD included change in tumor size by metastatic site, symptoms, and hospital utilization. Additionally, we characterized outcomes of pts who continued ICIs after rPOD. Fisher’s exact test was performed to identify potential clinical predictors of hospitalization at rPOD. Results: Of the 361 evaluable pts, 238 experienced rPOD. In this cohort, the most common primary sites of disease are: genitourinary (24%), thoracic (24%), skin (21%), and hepatobiliary (15%). At rPOD, 71 (30%) patients were hospitalized within 30 days, with infection (27%) and pain (18%) being the most common reasons. Median survival of pts with hospitalization was 2 months (mos; 95% CI: 0-4), compared to 10 months (95% CI: 8-12) for those not hospitalized (p

TPS174 Background: Bispecific antibodies (bsAbs) are emerging as a protein-based therapeutic strategy for directing T-cell-mediated cytotoxicity in a tumor antigen-specific manner, typically by binding to both tumor antigen and the CD3 receptor on T-cells. REGN5678 is a human IgG4-based, first-in-class costimulatory bsAb designed to target prostate tumors by bridging prostate specific membrane antigen expressing tumor cells with the costimulatory receptor, CD28, on T-cells, and providing amplified T-cell receptor-CD3 complex-mediated T-cell activation within the tumor through the activation of CD28 signaling. At the tumor site, REGN5678 may synergize with PD-1 inhibitors. In mouse models, REGN5678 in combination with a PD-1 antibody has improved anti-tumor activity compared with either therapy alone (Waite JC et al. Sci Transl Med. 2020:12;549). Methods: This is an open label, Phase I/II, first-in-human study evaluating safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of REGN5678 alone and in combination with cemiplimab in patients with metastatic castration resistant prostate cancer (mCRPC) who progressed after prior therapy (NCT03972657). For inclusion, patients must have received at least two prior lines of systemic therapy (in addition to androgen deprivation therapy) approved for metastatic and/or castration-resistant disease including a second-generation anti-androgen therapy. REGN5678 is administered weekly; cemiplimab (350 mg) is administered once every 3 weeks. During dose escalation, a 3-week safety lead-in of REGN5678 monotherapy will be administered prior to addition of cemiplimab. Study therapies are administered until disease progression, intolerable adverse events, withdrawal of consent, or study withdrawal criterion is met. The primary objectives in dose escalation are to evaluate safety, tolerability, and PK of REGN5678 alone and in combination with cemiplimab. Expansion cohort(s) will be enrolled once a maximum-tolerated REGN5678/cemiplimab dose is reached, or if a recommended Phase 2 dose or doses have been determined. During the expansion phase, the primary objective is to assess clinical activity, as measured by objective response rate of REGN5678 in combination with cemiplimab per modified Prostate Cancer Working Group 3 criteria. At selected sites, prostate-specific membrane antigen PET/CT scans are performed at baseline and select time points on study. This study is currently open to enrollment. Clinical trial information: NCT03972657.

e17105 Background: The success of randomized phase III therapeutic trials (RP3TT) to reach their primary endpoint is critical given the enormous resources required to conduct such studies. In an era of accelerated therapeutic development in advanced kidney cancer, we aim to identify factors in such studies associated with a positive endpoint (PE) to better understand how to optimize trial design. Methods: Using PubMed and ClinicalTrials.gov, we identified all published RP3TT in patients with metastatic renal cell carcinoma between 1/2007-9/2019. Studies were considered PE if the primary endpoint was reached, and negative endpoint (NE) if otherwise. Studies were categorized as either first line only (FLO) or second line and beyond (SLB), with adjuvant and consolidation therapy studies excluded. We collected components of study design and baseline patient characteristics and analyzed with multivariate logistic regression to evaluate the associations between each factor and PE RP3TT. Results: Of the 65 studies evaluated, only 22 RP3TT (14 FLO, 8 SLB) were found to have published data and were included, with 14 PE and 8 NE. For all studies, those with larger enrollment size (OR = 1.008, 95% CI [1.001-1.015], p = 0.021) and clear cell requirements (OR = 0.077, 95% CI [0.007-0.901], p = 0.041) were associated with PE. After adjusting for sample size, only larger enrollment size remained significant (OR = 1.007, 95% CI [1.001-1.014], p = 0.032). Other baseline patient demographic and clinical characteristic variables were not associated with PE RP3TT. Subgroup analysis of only FLO or SLB studies also did not yield any significant associations with PE RP3TT. Conclusions: Higher enrollment size was identified as factor associated with PE in RP3TT. Incomplete trial data reporting was evident, particularly in earlier studies. Further efforts are needed to better characterize factors in order to optimize clinical trial design in this disease. [Table: see text]

e15142 Background: Immune checkpoint inhibitors (ICIs) are increasingly utilized across cancer types. Risk factors for emergency room (ER) and inpatient (IP) care in this patient (pt) population remain poorly defined. Methods: We retrospectively reviewed charts for pts with (w/) advanced solid tumors who received more than 1 ICI dose at Mount Sinai from 1/1/11 – 4/28/17. Demographics, medical history, cancer diagnosis and therapy (tx) details, and outcomes were recorded. Descriptive data detailing ER/IP care during ICI tx (from first dose to 3 months after last dose) were collected. Fisher’s exact test and multivariable regression analyses were used to study differences between pts w/ versus w/out ER/IP care during ICI tx. Significance level was set at 0.05 for all tests. Results: 345 patients met the inclusion criteria for this study. Mean age was 64 years. Common tumor types were non-small cell lung cancer (n = 87), melanoma (n = 78), hepatocellular carcinoma (n = 53), and urothelial carcinoma (n = 38). 83% of patients had metastatic disease. Median duration of ICI tx was 2 months. During ICI tx, 50% received ER care and 43% received IP care, resulting in 369 total episodes of ER and/or IP care. 12% of episodes were attributed to ICI toxicity; 6% required intensive care. Median time to ER/IP care was 111 days. Median IP length of stay was 2 days. Several factors were found to be significant predictors of risk for ER or IP care on multivariable analysis (Table). African-American race and Hispanic ethnicity were each predictive of increased risk for both ER and IP care. Conclusions: ER/IP care is common among pts w/ advanced solid tumors on ICI tx. Understanding demographic and clinical risk factors can help prospectively identify higher-risk pts to inform preventive programs aimed at reducing such care. [Table: see text]

e17575 Background: Optimal sequencing of therapeutic agents in mCRPC remains debated, but the standard approach is to treat with one agent until resistance is met before switching. PRINT explores the efficacy of treating mCRPC with a rapidly-cycling, non-cross reactive regimen as a way to more effectively treat intrinsic heterogeneity, delay or prevent drug resistance, and minimize treatment toxicity. Methods: Patients received treatment with 3 consecutive treatment modules, each lasting 12 weeks: 1. abiraterone acetate 1000 mg PO daily + prednisone 5 mg PO BID; 2. cabazitaxel 20 mg/m2 IV + carboplatin AUC 4 IV q3 weeks; 3. enzalutamide 160 mg PO daily + radium-223 50 kBq/kg IV q4 weeks (in those with bone metastases). Upon completion of the 9-month regimen, patients are followed on ADT alone. Primary endpoint for the study is PSA or radiographic time to progression (TTP). Results: From 3/2017 to 1/2020, 38 of 40 planned men with mCRPC were enrolled, 28 patients have completed the 9-month study regimen and evaluable for TTP analysis. With median follow up of 54+ weeks, median time to PSA progression after therapy completion is 14.7+ weeks (95%CI; 5.5-23.9+ weeks). PSA response rates showed successive improvements with each sequential treatment module (Table). Eight patients (21.1%) continue on post-study surveillance with ADT alone, two of which have remained off any mCRPC agents for over a year (82+ weeks, 79+ weeks). In patients needing to restart therapy, experience with efficacy and tolerability of each agent while on the study, has helped inform subsequent mCRPC drug selection. The study regimen is well-tolerated, with few grade 3/4 AE’s: hyperglycemia (15.8%), diarrhea (5.3%), anemia (2.6%), fatigue (2.6%), neutropenia (2.6%), and thrombocytopenia (2.6%). Conclusions: Treatment of mCRPC with a rapidly-cycling non-cross reactive regimen demonstrates significant antitumor benefits, with potential for long-term suppression of disease. Further longitudinal follow up will determine if PRINT delays progression compared with standard approaches. Clinical trial information: NCT02903160 . [Table: see text]

e15097 Background: Improved immunotherapy (IO) outcomes have been observed among non-small cell lung cancer patients with a current or former smoking history. This is thought to be a consequence of increased immunogenic mutation burden among smoking-related cancers. We set out to explore the association between smoking status and immunotherapy outcomes in lung and other smoking-associated cancers. Methods: This was a retrospective analysis of 200 consecutive patients with advanced, smoking-associated solid tumor types, treated with single-agent anti-PD1/PDL1 therapy at a single center between July 2014 and February 2018. The primary outcome was overall survival from date of IO initiation. The secondary outcome was overall response, defined as radiographic complete response or partial response, by RECIST 1.1 criteria. The primary predictor was smoking status (former/current smoker vs. never smoker). The primary and secondary outcomes were analyzed using multivariable Cox proportional hazards models and multivariable logistic regression models, respectively. Models were adjusted for age and sex, and stratified by cancer type. Results: The majority of patients were male (64%) with a history of smoking (72%); the average age was 67.1 ± 11.4 years. Cancer types represented were: non-small cell lung cancer (NSCLC, N = 81), hepatocellular carcinoma (HCC, N = 41), urothelial carcinoma (BLCA, N = 39), head and neck squamous cell carcinoma (HNSC, N = 21), and renal cell carcinoma (RCC, N = 18). Over a median follow-up of 11.3 months (range 0.5-53.2), there were 96 deaths and 27% of evaluable patients achieved radiographic response. Response was not evaluable in 27 patients. In multivariable regression analysis, smoking status was not significantly associated with overall survival nor overall response in any cancer type examined (Table). Conclusions: Smoking status was not associated with outcomes in our cohort of IO-treated patients with smoking-associated cancers, though sample size was limited. [Table: see text]

e15160 Background: Development (DV) of immune-related adverse events (IRAEs) to immune checkpoint inhibitor (ICI) have been associated (asso/) with (w/) favorable treatment (tx) response, but heterogeneity in clinical presentation remains a concern. We aim to characterize the type, timing, and risk factors asso/ w/ IRAE DV in ICI-treated solid tumor (ST) patients (pts). Methods: The characteristics (char), tx course, and clinical outcomes of ST pts who received at least 2 ICI doses at our institution from 1/1/2011 to 4/29/2017 were reviewed. IRAEs were identified and graded (GR) based on CTCAE (v.4.0). Fisher’s exact test and multivariable regression analyses (MVA) were performed to study the differences between pts w/ versus without (w/o) IRAE. Results: Of the 344 pts identified, 111 pts (32%) had IRAE(s) w/ 145 total events (GR 1: 31%, GR 2: 57%, GR 3: 12%), of which 45% required systemic steroids (SS), 27% lead to ICI discontinuation (DC), and 17% lead to hospitalization (HP, Table). Median time to any IRAE was 12 weeks (w, range 1-149.5w). The most common IRAEs were endocrine (30%), gastrointestinal (GI, 28%), and skin (24%) related. On univariable analysis, antibiotic use, melanoma, and combination ICI use were asso/ w/ IRAE DV; melanoma remained significant on MRA (odds ratio, OR: 3.58 [1.68, 7.64], p = 0.0010). Pts w/ IRAE had higher disease control rate (complete/partial response + stable disease) than pts w/o IRAE (OR: 2.20 [1.29, 3.75], p = 0.0038). Conclusions: Our real-world data showed higher IRAE incidence when compared to those reported in trials, although no GR 4/5 IRAEs occurred. Melanoma was asso/ w/ IRAE DV on MRA, possibly due to the type, dose, and combination of ICIs. These findings warrant further investigation to better identify those at the highest risk to develop clinically significant IRAE. [Table: see text]