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Purpose: The PURE-01 study (NCT02736266) pioneered the neoadjuvant immune-checkpoint inhibitor (ICI) therapy before radical cystectomy (RC) in patients with muscle-invasive urothelial bladder carcinoma (MIBC). We herein present the survival outcomes after a median follow-up of three years. Patients and Methods: The intention-to-treat (ITT) population included 155 patients. Event-free survival (EFS) was defined as the time from pembrolizumab initiation until radiographic disease progression precluding RC, initiation of neoadjuvant chemotherapy, recurrence after RC, or death. Further outcomes were recurrence-free survival (RFS) post-RC and overall survival (OS). Multivariable Cox regression analyses for EFS were performed. Kaplan–Meier analyses compared EFS outcomes according with baseline programmed cell-death-ligand-1 (PD-L1) combined positive score (CPS) and according to the molecular subtypes. Results: After a median (interquartile range, IQR) follow-up of 39 (30–47) months, 36-month EFS and OS were 74.4% [95% confidence interval (CI), 67.8–81.7] and 83.8% (95% CI, 77.8–90.2) in the ITT population, respectively. Overall, 143 (92.3%) patients underwent RC. Within the cohort of patients who did not receive additional chemotherapy (N = 125), 36-month RFS was 96.3% (95% CI, 91.6–100) for patients achieving a ypT0N0, 96.1% (95% CI, 89–100) for ypT1/a/isN0, 74.9% (95% CI, 60.2–93) for ypT2–4N0, and 58.3% (95% CI, 36.2–94.1) for ypTanyN1–3 response. EFS was significantly stratified among PD-L1 tertiles (lower tertile: 59.7% vs. medium tertile: 76.7% vs. higher tertile: 89.8%, P = 0.0013). The claudin-low and basal/squamous subtypes displayed the lowest rates of events. Conclusions: At a median follow-up of three years, PURE-01 results further confirm the sustained efficacy of neoadjuvant pembrolizumab before RC. PD-L1 expression was the strongest predictor of sustained response post-RC.

Purpose:The PURE-01 study (NCT02736266) pioneered the neoadjuvant immune-checkpoint inhibitor (ICI) therapy before radical cystectomy (RC) in patients with muscle-invasive urothelial bladder carcinoma (MIBC). We herein present the survival outcomes after a median follow-up of three years.Patients and Methods:The intention-to-treat (ITT) population included 155 patients. Event-free survival (EFS) was defined as the time from pembrolizumab initiation until radiographic disease progression precluding RC, initiation of neoadjuvant chemotherapy, recurrence after RC, or death. Further outcomes were recurrence-free survival (RFS) post-RC and overall survival (OS). Multivariable Cox regression analyses for EFS were performed. Kaplan–Meier analyses compared EFS outcomes according with baseline programmed cell-death-ligand-1 (PD-L1) combined positive score (CPS) and according to the molecular subtypes.Results:After a median (interquartile range, IQR) follow-up of 39 (30–47) months, 36-month EFS and OS were 74.4% [95% confidence interval (CI), 67.8–81.7] and 83.8% (95% CI, 77.8–90.2) in the ITT population, respectively. Overall, 143 (92.3%) patients underwent RC. Within the cohort of patients who did not receive additional chemotherapy (N = 125), 36-month RFS was 96.3% (95% CI, 91.6–100) for patients achieving a ypT0N0, 96.1% (95% CI, 89–100) for ypT1/a/isN0, 74.9% (95% CI, 60.2–93) for ypT2–4N0, and 58.3% (95% CI, 36.2–94.1) for ypTanyN1–3 response. EFS was significantly stratified among PD-L1 tertiles (lower tertile: 59.7% vs. medium tertile: 76.7% vs. higher tertile: 89.8%, P = 0.0013). The claudin-low and basal/squamous subtypes displayed the lowest rates of events.Conclusions:At a median follow-up of three years, PURE-01 results further confirm the sustained efficacy of neoadjuvant pembrolizumab before RC. PD-L1 expression was the strongest predictor of sustained response post-RC.

Surgical safety outcomes in PURE-01 trial

Distribution of the GSC subtypes according to the Consensus Bladder Cancer classification.

Distribution of the GSC subtypes according to the TCGA classification.

Updated adverse events observed in ITT population

Representativeness of study participants

Supplementary Figure 1: Study flow-chart. Supplementary Figure 2: Kaplan-Meier curves of event-free survival according to tertile-split tumor mutational burden. Supplementary Figure 3. Kaplan-Meier curves of recurrence-free survival according to the molecular subtype. Supplementary Figure 4: PD-L1 staining values (CPS percentages) according to molecular subtypes, split by the three subtyping classifiers GSC/Decipher, Consensus classification, and TCGA.

Adrenocortical carcinoma (ACC) is a very rare endocrine cancer and is associated with a poor prognosis. There is a paucity of randomized clinical trials for this rare disease. We aimed to perform a systematic review of the literature on systemic therapy options in different stages of ACC. A systematic review was performed using Pubmed and Embase databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 24 trials of systemic therapy in the treatment of ACC were identified and included in this review. Only one clinical trial in the adjuvant setting was identified, the negative phase III trial ADIUVO, which tested mitotane in low to intermediate-risk ACC patients. In the treatment of advanced ACC, cisplatin-based chemotherapy was evaluated in small and non-randomized phase II trials, and response rates ranged from 21% to 53.5%. The phase III trial FIRM-ACT compared etoposide, doxorubicin, cisplatin, and mitotane versus treatment with streptozotocin and mitotane and showed no difference in OS, but higher RR and PFS were reported with the multi-drug regimen. Six clinical trials of immunotherapy and seven studies of targeted therapy in advanced ACC were included, with modest activity and no phase 3 trials were identified. Treatment recommendations of ACC are based on retrospective and small studies with limited systemic therapy options. International and multi-center collaboration is essential to expand clinical research and improve outcomes.

Metastatic urothelial cancer (mUC) is an aggressive disease with limited overall survival and treatment options. Antibody-drug conjugates (ADCs) were designed with the intent to deliver potent cytotoxic drugs selectively to antigen-expressing tumor cells by linking cytotoxins to monoclonal antibodies (mAbs) and have emerged as new treatment options in mUC, mainly in chemotherapy (CT) and immune-checkpoint inhibitors (ICI)-exposed patients. We aimed to perform a scoping review to assess activity, efficacy, treatment-related adverse events (TRAEs), and impact on quality of life of ADCs in mUC.A review of the literature was performed in January 2022 using Pubmed and Embase databases according to the recommendations of the Joanna Briggs Institute. The search method involved querying for the terms "bladder carcinoma" or "urothelial carcinoma" with any of the following: "enfortumab vedotin" (EV), "sacituzumab govitecan" (SG), antibody-drug conjugate. Only prospective clinical trials were included.Ultimately, eleven clinical trials with 1417 patients were selected for inclusion, and five drugs were identified: enfortumab vedotin (EV), sacituzumab govitecan (SG), disitamab vedotin (RC48-ADC), ASG-15ME (anti-SLITRK6), and trastuzumab deruxtecan. The different ADCs have been tested mainly in phase 1 or phase 2 trials, as monotherapy or in combination with ICI. Response rate ranged from 27% with SG in previously treated patients to 73.3% with EV plus pembrolizumab in cisplatin-ineligible patients as first-line treatment. The phase 3 trial, EV-301, confirmed EV superiority over investigator-chosen CT after failure to platinum-based CT and ICI, improving overall survival (12.88 vs. 8.97 months; HR 0.70; 95% CI, 0.56-0.89; P=0.001). TRAEs of any grade occurred in more than 90% of patients in phase 2 or 3 trials, with high rates of grade 3 ≥ events ranging from 51.4 to 73.5% in different trials. TRAEs of particular interest related to EV were rash, neuropathy, and hyperglycemia. SG was associated with diarrhea and hematologic toxicity. Data from phase 2 and 3 trials of EV suggest no impact on quality of life but an improvement in pain symptoms compared to the control arm.ACDs represent a new therapeutic option for the treatment of mUC. Level-1 evidence has already been achieved by EV in the post-CT and post-ICI settings. A high incidence of potential adverse events was observed in phase 2 and 3 trials, including rash, neutropenia, hematologic toxicity, and neuropathy. Clinicians should be aware of possible adverse events and their optimal management.

454 Background: According to population-based studies, there is a significant racial difference in patient characteristics, incidence, and survival among bladder cancer patients. Non-Hispanic whites have the highest incidence rate, followed by blacks. However, racial clinical trial disparities in clinical research are a critical problem around the world, with an underrepresentation of the black population. In the last years, multiple phase 2/3 trials have introduced the use of immunotherapy and targeted therapy in the treatment of bladder cancer. We aimed to assess the enrollment disparities in pivotal BC clinical trials. Methods: Published clinical trials were identified from the Bladder Cancer European Society of Medical Oncology (ESMO) guideline, considering the approved drugs and availability in clinical practice. The characteristics of participants, including race and geographic location, were collected. Results: A total of 1 phase 2 or 3 trials were identified, evaluating pembrolizumab, atezolizumab, avelumab, erdafitinib, durvalumab +/- tremelimumab and enfortumab vedotin, with a total of 7748 patients. The table summarizes the findings. Race information is available only in 8 of them, 4 in the original report and 4 in the results section of clinicaltrials.gov, with a pooled sample of 6573 patients. White, Asian and Black patients comprised 71.74% (4716 pts), 19.9% (1313 pts), and 0.66% (44 pts) of all patients, respectively. The percentage of white patients ranged from 51.6% to 88.6%, whereas the black population varied from 0.3% to 2.2%. Geographical location information is available only for 2 clinical trials, with a predominance of patients from the United States and Europe and an under-representation of patients from other continents. Conclusions: We observed a low rate of race reporting in bladder cancer published trials and a very significant under-representation of non-white participants in the pivotal trials for bladder cancer, with just 0.66% of black patients. Based on these finding, there are insufficient data to confirm the effectiveness or safety of new drugs in minority groups, especially blacks. To provide generalizable results, race reporting should be always included in licensing trials, and recruitment of black and other minority population to trials should be stimulated.[Table: see text]

552 Background: The possibility to predict the pathologic complete response (pT0) or downstaging (pT≤1) after neoadjuvant therapy may have profound impact on the management of MIBC and orient next-generation bladder-sparing trials. The VIRADS is a standardized reporting system that uses mpMRI parameters to predict the probability of MIBC. No studies have analyzed the ability of VIRADS to predict the pT0 or pT≤1 response post-immunotherapy (IO). Methods: In PURE-01 patients (pts) were staged with bladder multiparametric magnetic resonance imaging (mpMRI: T2-weighted imaging, diffusion-weighted imaging, dynamic contrast enhancement) before and after treatment (3 cycles of pembro) prior to radical cystectomy (RC). All mpMRI scans were centrally reviewed. Logistic regression models analyzed pre- and post-pembro VIRADS against pT≤1 (primary endpoint) and pT0 (secondary endpoint). VIRADS scores were dichotomized between 0-3 and 4-5. Covariates included cT-stage, age, gender, PD-L1 combined positive score (CPS) and tumor mutational burden (TMB). Results: In total, 58 pts were had centrally-reviewed MRI scans (N=116 mpMRI), treated between 02/17 and 08/18. Demographic characteristics and outcomes were generally similar between the all-treated and VIRADS-evaluable populations of PURE-01. Median age was 65 years, 52 (89%) had pure/predominant urothelial carcinoma (UC) histology, 25 (43.1%) had cT3-4N0 MIBC. Pre-pembro: 8 pts (13.8%) had no measurable disease (VIRADS=0), 20 (34.5%) a VIRADS 1-3 score, and 30 (51.7%) had a VIRADS 4-5 score. Six pts (10.3%) had a downstage from VIRADS 4-5 to VIRADS 0-3 post-pembro. Both pre-pembro and post-pembro VIRADS 0-3 scores were significantly associated with pT≤1 endpoint on multivariable analyses (MVA): the strongest effect was seen with post-pembro VIRADS 0-3 against pT≤1 response (OR: 30.2, 95%CI: 6.2-223.2, p

549 Background: The PURE-01 clinical trial reported the use of neoadjuvant treatment with pembrolizumab prior to radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC; cT2–3N0M0; PMID 30343614). We have previously reported that specific molecular subtypes (i.e. basal or claudin-low) and immune signatures are associated with more favorable survival. However, reports on the detailed tumor biology of patients (pts) who relapsed after neoadjuvant pembrolizumab are lacking. Herein, we provide a detailed characterization of relapsing pts and identify distinct gene expression patterns with potential utility as novel biomarkers. Methods: Microarray data from transurethral resection of the bladder tumor (TURBT; N=102) and matched RC (N=25) tissue from the PURE-01 trial were analyzed. Gene expression signatures and molecular subtypes were assigned as previously described (PMID 32165065). The Kaplan-Meier method was used to estimate differences in patient outcomes. Immune-signatures were split by median for survival analysis. All significance testing used a two-sided t-test at a threshold of 0.05. Results: Differential gene expression analysis identified KRT20 and H19 to be enriched in relapsing patients (both p

e16536 Background: mUC is an aggressive disease with limited overall survival. Recently, immunotherapy with checkpoint inhibitors (ICI) has dramatically improved outcomes but with limited response rates and overall survival. ADC were designed with the intent to deliver potent cytotoxic drugs selectively to antigen-expressing tumor cells by linking cytotoxins to mAbs and have emerged as a new option of treatment with promising results. We aimed to realize a systematic review of efficacy, treatment-related AEs (trAEs) and impact on quality of life of ADC in mUC. Methods: A systematic review of the literature has been performed in January 2022 using Pubmed and Embase database according to the Preferred Reported Items for Systematic Reviews and Meta-analyses (PRISMA) statement. After excluding review, duplicate and non-relevant articles, 10 clinical trials were included in the analysis. The search method involved querying for the terms bladder carcinoma or urothelial carcinoma with any of the following: enfortumab vedotin (EV), sacituzumab govitecan (SG), antibody-drug conjugate. Only prospective clinical trials were included. Results: The systematic review yielded 1103 records using MEDLINE (741 records) and EMBASE (362 records). Ultimately, 9 phase 1, 2 or 3 clinical trials with 1355 patients were selected for inclusion and 4 drugs were identified: Enfortumab vedotin (EV), sacituzumab govitecan (SG), an anti-HER2 compound (RC48-ADC), and an anti- SLITRK6 drug (ASG-15ME). Efficacy outcomes are presented in table 1. Phase 2 trials have reported promising response rates in mUC and one randomized phase 3 trial showed the superiority of EV vedotin over CT after failure to platinum-based CT and ICI with improvement in overall survival. TRAEs of any grade occurred in more than 90% of patients in phase 2 or 3 trials, with high rates of discontinuation (table 2). TRAEs of special interest related to EV were rash, neuropathy, and hyperglycemia. SG is associated with diarrhea and hematologic toxicity. Data from phase 2 and 3 trials of EV suggest no impact on quality of life and an improvement in some parameters. Conclusions: ACDs represent a very promising new option for the treatment of mUC. A phase 3 trial confirmed the superiority of EV over CT after platinum and IO failure. A high incidence of potential adverse events was observed in phase 2 and 3 trials, including rash, neutropenia, hematologic toxicity, and neuropathy. Practitioners’ oncologists should be aware of potential adverse events and optimal management. Quality of life is preserved during the treatment with EV.

e16501 Background: Clear cell carcinoma (RCC) is the most common histologic type of renal cancer. It is well established that, for this specific histology, six main prognostic factors interact into a score and can categorize it into three different prognostic groups: favorable-risk, intermediate-risk, and poor-risk. These six factors are anemia, thrombocytosis, neutrophilia, hypercalcemia, Karnofsky performance status < 80%, and < 1 year from diagnosis to treatment. The objective of this study is to evaluate if any of these prognostic factors can independently predict a worse prognosis. Methods: We conducted a retrospective study with 51 patients treated in our national reference institution. The great majority of them were RCC. We analyzed the overall survival (OS) of each one of the six classic risk factors adding to that the body mass index (BMI), the presence of metastasis at diagnosis time, and comorbidities. Results: The analysis of most of the indexed parameters did not show a statistical difference, but anemia and the presence of metastasis at the time of diagnosis. We found that the anemia itself denotes a Hazard Ratio (HR) of 2,35 (p = 0,034). Moreover, if it is adjusted for age and sex, the HR reduces at 1,149, sustaining its statistical significance yet. The presence of metastasis at the time of diagnosis is translated as an HR = 2,029 (p = 0,049), bringing into light something already known in clinical practice, but still, a lower risk compared to anemia. Conclusions: The six classic risk factors for RRC survival pooled together can interact and predict the OS and patient’s prognosis. Our study suggests that the anemia itself can predict independently a worst-case scenario, which emphasizes the importance of this analysis upfront. A larger prospective cohort is warranted to further understanding this framework.

e13600 Background: The COVID-19 infection was declared pandemic in March 2020. Since then, multiple studies have attempted to correlate clinical factors with risk of complications from COVID-19, including cancer. However, cancer patients are underrepresented in clinical trials and the results vary between different cohorts. Methods: We conducted a multicentre retrospective study, based on systematic review of medical records, including nine cancer centers, located in five different Brazilian cities. Patients were diagnosed with COVID-19 through RT-PCR between March 15, 2020 and August 13 , 2020. Poisson regression models were then used to test for an association between clinical characteristics and severity of COVID-19 infections. Results: 102 patients had data collected for analysis, 85 (83.3%) of whom were hospitalized due to complications from COVID-19 infection. The median age was 65.8 years, most were female patients (61.8%) and white (73,5%). 78.4% had a performance status of 0-1, and the most common cancer subtypes were gastrointestinal (30.4%), breast (22.6%) and hematological (13.7%). Almost 40% of population had stage IV disease. Mortality rate for all hospitalized patients was 36.5%, while for those admitted to the ICU it was 68.4%. Key univariable risk factors for mortality included age (RR 1.03), ECOG ≥ 2 (RR 1.83), hypertension (RR 1.72), lung metastasis (RR 1.67), and lymphocytes ≤ 1000 admission (RR 2.40). At the multivariable analysis, the risk factors were also age (RR 1.02), primary lung cancer (RR 2.61), lung metastasis (RR 2.86), and coronary disease (RR 3.76). Conclusions: Despite the high mortality of patients hospitalized with COVID-19, our data are compatible with other cohorts. Cancer patients must be carefully monitored in pandemic periods of infectious diseases.

e18171 Background: The perception of symptoms, diagnosys, access to a cancer care institute and the first-line of therapy are milestones of cancer care. The success of an oncological treatment is directly relatable to these key-points and the time gaps between them. Growing research in developing countries points out the challenges of offering quality of care in this setting as social, cultural, economic and political factors are deeply intertwined. The objective of this study is to identify the key-points of cancer care, the time gaps between them and the time-related end-points of patients refered to a medical oncology department of a public university hospital in São Paulo, Brazil, in the period of one year. Methods: This is a observational retrospective study based on review of medical records of all cancer patients refered to the medical oncology department of a public university hospital in São Paulo, Brazil, from 01/01/17 to 12/31/17. The analysis was performed in January 2019. The data collected comprises the age at diagnosys, gender, primary tumor site, stage (AJCC 7th ed. staging system), onset of symptons, date of hystopathological diagnosys, the first therapeutic modality and when it was offered, intention of care (curative or palliative), outcomes and the following time-relations: symptoms-dyagnosis (SD), dyagnosis-treatment (DT) and symptoms-treatment (ST). Results: From 358 profiles, 275 were included. The average age at diagnosys was 58,7 years (15-88 years). Men were 147 (53,4%) and 128 (46,5%) were women. The most common primary tumor sites were gastrointestinal tract 22,9%, head and neck 20,3%, cutaneous melanoma 17,8% and genitourinary tract 16%. 160 (58,1%) patients were diagnosed at advanced/metastatic stages (III/IV). The median time-relations were: 5,5 months for SD; 2 months for DT and 8 months for ST. The first treatment offered was surgery at 63,2% of cases, radiotherapy 17,8%, systemic therapy 16,7% (endocrine therapy, targeted therapy or chemotherapy) or palliative care 1,8%. The intention of the initial treatment: 76,3% were curative and 23,2% palliative. At time of analysis, 63,6% of patients were alive, 19,2% deceased and 16,7% of unknown outcome. Conclusions: Our data endorses prevalent findings of developing countries epidemiological studies: late diagnosys, non-curative treatments and poor outcomes. Known causes are desfavorable social-economic conditions, symptom neglection, ineffective cancer screening and deficiency of public cancer care networks. We emphasize time goals as important quality indexes to guide new solutions.

e18041Background: HNSCC has a high incidence around the world and in Brazil it is one of the most common malignancies. Hematologic markers represent a measurable parameter of host inflammation with...

Purpose Among renal malignancies, renal cell carcinoma (RCC) accounts for 85% of cases. Stage is a relevant prognostic factor; 5-year survival ranges from 81% to 8% according to the stage of disease. The treatment is based on surgery and molecularly targeted therapy has emerged as a choice for metastatic disease. Materials and Methods Retrospective study by reviewing the medical records of patients with RCC treated in the last 10 years at UNIFESP. The primary end point of this trial was to evaluate the overall survival (OS) of the patients. The secondary end point was to evaluate the progression-free survival (PFS) after nephrectomy. Results 118 patients with RCC were included. The mean age was 58.3 years, 61.9% men; nephrectomy was performed in 90.7%, clear cell was the histology in 85.6%, 44 patients were classified as stage IV at diagnosis. Among these, 34 had already distant metastasis. 29 patients were treated with sunitinib. The median OS among all patients was 55.8 months. The median PFS after nephrectomy was 79.1 months. Sarcomatoid differentiation HR29.74 (95% CI, 4.31-205.26), clinical stage IV HR1.94 (95% CI, 1.37-2.75) and nephrectomy HR0.32 (95% CI, 0.15-0.67) were OS prognostic factors. Sunitinib had clinical activity. Conclusions Patients treated in our hospital achieved median OS compatible with literature. Nevertheless, this study has shown a high number of patients with advanced disease. For patients with advanced disease, treatment with sunitinib achieved median OS of 28.7 months, consistent with the literature.

Recently, the development of antiangiogenic drugs has changed the therapy for metastatic renal cell carcinoma (RCC). As a result, the survival of individuals with advanced RCC has more than doubled. The median overall survival improved from 12 months during the cytokines era to near 30 months with antiangiogenic drugs. In this decade, the advent of immune checkpoint inhibitors showed enthusiastic results and is the new standard of care for patients with metastatic RCC previously treated with antiangiogenic drugs. The combination of immune checkpoint inhibitors plus antiangiogenic drugs may have a synergistic activity. As a result, current studies investigate the combination for treatment-naïve patients. This may potentially change clinical practice. In this article, we will highlight new therapeutic options available and agents or combinations that are being investigated for metastatic RCC.