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To examine patient and disease characteristics, toxicity, and clinical outcomes for patients with advanced urothelial carcinoma (aUC) who are rechallenged with immune checkpoint inhibitor (ICI)-based therapy.In this retrospective cohort, we included patients treated with ICI for aUC after having prior ICI treatment. Endpoints included the evaluation of radiographic response and disease control rates with first and second ICI courses, outcomes based on whether there was a change in ICI class (anti-PD-1 vs. anti-PD-L1), and assessment of the reasons for ICI discontinuation.We identified 25 patients with aUC from 9 institutions who received 2 separate ICI courses. ORR with first ICI and second ICI were 39% and 13%, respectively. Most patients discontinued first ICI due to progression (n = 19) or treatment-related toxicity (n = 4). Thirteen patients received non-ICI treatment between the first and second ICI, and 12 patients changed ICI class (anti-PD-1 vs. anti-PD-L1) at rechallenge. Among 10 patients who changed ICI class, 8 (80%) had progressive disease as best response with second ICI, while among 12 patients re-treated with the same ICI class, only 3 (25%) had progressive disease as best response at the time of rechallenge. With second ICI, most patients discontinued treatment due to progression (n = 18) or patient preference (n = 2).A proportion of patients with aUC rechallenged with ICI-based regimens may achieve disease control, supporting clinical trials in that setting, especially with ICI-based combinations. Future studies are needed to validate our results and should also focus on identifying biomarkers predictive of benefit with ICI rechallenge.

PURPOSE: Patients with metastatic cancer benefit from advance care planning (ACP) conversations. We aimed to improve ACP using a computer model to select high-risk patients, with shorter predicted survival, for conversations with providers and lay care coaches. Outcomes included ACP documentation frequency and end-of-life quality measures. METHODS: In this study of a quality improvement initiative, providers in four medical oncology clinics received Serious Illness Care Program training. Two clinics (thoracic/genitourinary) participated in an intervention, and two (cutaneous/sarcoma) served as controls. ACP conversations were documented in a centralized form in the electronic medical record. In the intervention, providers and care coaches received weekly e-mails highlighting upcoming clinic patients with < 2 year computer-predicted survival and no prior prognosis documentation. Care coaches contacted these patients for an ACP conversation (excluding prognosis). Providers were asked to discuss and document prognosis. RESULTS: In the four clinics, 4,968 clinic visits by 1,251 patients met inclusion criteria (metastatic cancer with no prognosis previously documented). In their first visit, 28% of patients were high-risk (< 2 year predicted survival). Preintervention, 3% of both intervention and control clinic patients had ACP documentation during a visit. By intervention end (February 2021), 35% of intervention clinic patients had ACP documentation compared with 3% of control clinic patients. Providers' prognosis documentation rate also increased in intervention clinics after the intervention (2%-27% in intervention clinics, P < .0001; 0%-1% in control clinics). End-of-life care intensity was similar in intervention versus control clinics, but patients with ≥ 1 provider ACP edit met fewer high-intensity care measures ( P = .04). CONCLUSION: Combining a computer prognosis model with care coaches increased ACP documentation.

There is significant racial disparity in thoracic malignancies in terms of epidemiology and outcomes. We analyzed race reporting and racial diversity in the registration trials of drugs approved by the FDA for thoracic malignancies from 2006 to 2020. We found a significant under-representation of non-white participants in FDA drug registration trials in thoracic malignancies. Furthermore, though almost all trials report some race information, FDA guidelines are not universally followed. There is a disproportionate disease burden of lung cancer in under-represented race communities, and clinical trials should prioritize racial diversity and inclusion efforts.

Over the past decade, the emergence of immune checkpoint inhibitors has brought about significant change to the treatment landscape of bladder cancer. Nivolumab is an immune checkpoint inhibitor that has shown favorable results resulting in FDA approval for treatment of platinum-refractory locally advanced or metastatic urothelial carcinoma. More recently, it was the first (and only) immune checkpoint inhibitor to receive FDA approval for the treatment of urothelial carcinoma in the adjuvant setting after radical surgery. Multiple trials are now actively underway to further understand the nuances in which immune checkpoint inhibitors such as nivolumab can be beneficial. In this review, we explore the development of nivolumab in terms of its mechanism of action, its growing indications in the treatment of urothelial carcinoma, and potential future directions for clinical trials. Immune checkpoint inhibitors are a promising treatment for bladder cancer, but further work is needed to continue to improve outcomes for patients.

Immune checkpoint inhibitors are a well-established treatment option for advanced urothelial carcinoma, and biomarkers of response are needed for better patient selection. We show that metastatic disease confined to lymph nodes is associated with better outcomes, while metastases to liver, bone or both are associated with poor outcomes with immune checkpoint inhibitor therapy. Results are hypothesis-generating but relevant to practice. BACKGROUND: Sites of metastasis have prognostic significance in advanced urothelial carcinoma (aUC), but more information is needed regarding outcomes based on metastatic sites in patients treated with immune checkpoint inhibitors (ICI). We hypothesized that presence of liver/bone metastases would be associated with worse outcomes with ICI. METHODS: We identified a retrospective cohort of patients with aUC across 26 institutions, collecting demographics, clinicopathological, treatment, and outcomes information. Outcomes were compared with logistic (observed response rate; ORR) and Cox (progression-free survival; PFS, overall survival; OS) regression between patients with/without metastasis beyond lymph nodes (LN) and those with/without bone/liver/lung metastasis. Analysis was stratified by 1st or 2nd(+) line. RESULTS: We identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (Hazard ratio; HR: 1.65 and 2.54), OS (HR: 1.60 and 2.35, respectively) and lower ORR (OR: 0.48 and 0.31). In the 2nd(+) line, bone/liver metastases were associated with shorter PFS (HR: 1.71 and 1.62), OS (HR: 1.76 and 1.56) and, for bone-only metastases, lower ORR (OR: 0.29). In the 1st line, LN-confined metastasis was associated with longer PFS (HR: 0.53), OS (HR:0.49) and higher ORR (OR: 2.97). In the 2nd(+) line, LN-confined metastasis was associated with longer PFS (HR: 0.47), OS (HR: 0.54), and higher ORR (OR: 2.79); all associations were significant. CONCLUSION: Bone and/or liver metastases were associated with worse, while LN-confined metastases were associated with better outcomes in patients with aUC receiving ICI. These findings in a large population treated outside clinical trials corroborate data from trial subset analyses.

Among 2,186 U.S. adults with invasive cancer and laboratory-confirmed SARS-CoV-2 infection, we examined the association of COVID-19 treatments with 30-day all-cause mortality and factors associated with treatment. Logistic regression with multiple adjustments (e.g., comorbidities, cancer status, baseline COVID-19 severity) was performed. Hydroxychloroquine with any other drug was associated with increased mortality versus treatment with any COVID-19 treatment other than hydroxychloroquine or untreated controls; this association was not present with hydroxychloroquine alone. Remdesivir had numerically reduced mortality versus untreated controls that did not reach statistical significance. Baseline COVID-19 severity was strongly associated with receipt of any treatment. Black patients were approximately half as likely to receive remdesivir as white patients. Although observational studies can be limited by potential unmeasured confounding, our findings add to the emerging understanding of patterns of care for patients with cancer and COVID-19 and support evaluation of emerging treatments through inclusive prospective controlled trials.Significance:Evaluating the potential role of COVID-19 treatments in patients with cancer in a large observational study, there was no statistically significant 30-day all-cause mortality benefit with hydroxychloroquine or high-dose corticosteroids alone or in combination; remdesivir showed potential benefit. Treatment receipt reflects clinical decision-making and suggests disparities in medication access.This article is highlighted in the In This Issue feature, p. 1426

Supplemental tables, figures, and list of participants

OBJECTIVES: To compare clinical outcomes with programmed-death ligand-1 immune checkpoint inhibitors (ICIs) in patients with advanced urothelial carcinoma (aUC) who have vs have not undergone radical surgery (RS) or radiation therapy (RT) prior to developing metastatic disease. PATIENTS AND METHODS: We performed a retrospective cohort study collecting clinicopathological, treatment and outcomes data for patients with aUC receiving ICIs across 25 institutions. We compared outcomes (observed response rate [ORR], progression-free survival [PFS], overall survival [OS]) between patients with vs without prior RS, and by type of prior locoregional treatment (RS vs RT vs no locoregional treatment). Patients with de novo advanced disease were excluded. Analysis was stratified by treatment line (first-line and second-line or greater [second-plus line]). Logistic regression was used to compare ORR, while Kaplan–Meier analysis and Cox regression were used for PFS and OS. Multivariable models were adjusted for known prognostic factors. RESULTS: We included 562 patients (first-line: 342 and second-plus line: 220). There was no difference in outcomes based on prior locoregional treatment among those treated with first-line ICIs. In the second-plus-line setting, prior RS was associated with higher ORR (adjusted odds ratio 2.61, 95% confidence interval [CI]1.19–5.74]), longer OS (adjusted hazard ratio [aHR] 0.61, 95% CI 0.42–0.88) and PFS (aHR 0.63, 95% CI 0.45–0.89) vs no prior RS. This association remained significant when type of prior locoregional treatment (RS and RT) was modelled separately. CONCLUSION: Prior RS before developing advanced disease was associated with better outcomes in patients with aUC treated with ICIs in the second-plus-line but not in the first-line setting. While further validation is needed, our findings could have implications for prognostic estimates in clinical discussions and benchmarking for clinical trials. Limitations include the study’s retrospective nature, lack of randomization, and possible selection and confounding biases.

e18644 Background: Assessments of health-related quality of life (HRQOL) are conducted by health systems to analyze and improve patient-centered care. Numerous studies have shown that the COVID-19 pandemic poses unique stressors for patients with cancer. However, the impact of the pandemic on HRQOL in patients with cancer is unknown. This study investigates change in self-reported global health scores in patients with cancer before and during the COVID-19 pandemic. Methods: In this single-institution retrospective cohort study, patients who completed the Patient-Reported Outcomes Measurement Information System (PROMIS) at a comprehensive cancer center before and during the COVID-19 pandemic were identified. Surveys were analyzed to assess change in the PROMIS global mental health (GMH) and global physical health (GPH) scores at different time periods (pre-COVID: 3/1/5/2019-3/15/2020, surge1: 6/17/2020-9/7/2020, valley1: 9/8/2020-11/16/2020, surge2: 11/17/2020-3/2/2021, and valley2: 3/3/2021-6/15/2021). Results: A total of 29,983 surveys among 7,209 patients were included in the study. Mean GMH scores for patients before the COVID-19 pandemic (50.57) were similar to that during various periods during the pandemic: surge1 (48.82), valley1 (48.93), surge2 (48.68), valley2 (49.19). Mean GPH score was significantly higher pre-COVID (42.46) than during surge1 (36.88), valley1 (36.90), surge2 (37.33) and valley2 (37.14) (Table). During the pandemic, mean GMH (49.00) and GPH (37.37) scores obtained through in-person were similar to mean GMH (48.53) and GPH (36.94) scores obtained through telehealth. Conclusions: In this single institution study, patients with cancer reported stable mental health and deteriorating physical health during the COVID-19 pandemic as indicated by the PROMIS survey. Modality of the survey (in-person versus telehealth) did not affect scores. [Table: see text]

Immune checkpoint inhibitors improve overall survival in advanced urothelial carcinoma, but response rates remain modest. We performed a multi-institutional retrospective cohort study comparing outcomes (observed response rate, progression-free, and overall survival) between patients based on time from initiation of first line platinum-based chemotherapy to second line immune checkpoint inhibitor. This study provides preliminary data that earlier resistance to platinum-based chemotherapy may be associated with shorter survival in those who receive subsequent ICI. BACKGROUND: Early progression on first-line (1L) platinum-based therapy or between therapy lines may be a surrogate of more aggressive disease and poor outcomes in advanced urothelial carcinoma (aUC), but its prognostic role regarding immune checkpoint inhibitor (ICI) response and survival is unclear. We hypothesized that shorter time until start of second-line (2L) ICI would be associated with worse outcomes in aUC. PATIENTS AND METHODS: We performed a retrospective multi-institution cohort study in patients with aUC treated with 1L platinum-based chemotherapy, who received 2L ICI. Patients receiving switch maintenance ICI were excluded. We defined time to 2L ICI therapy as the time between the start of 1L platinum-based chemotherapy to the start of 2L ICI and categorized patients a priori into 1 of 3 groups: less than 3 months versus 3–6 months versus more than 6 months. We calculated overall response rate (ORR) with 2L ICI, progression-free survival (PFS) and overall survival (OS) from the start of 2L ICI. ORR was compared among the 3 groups using multivariable logistic regression, and PFS, OS using cox regression. Multivariable models were adjusted for known prognostic factors. RESULTS: We included 215, 215, and 219 patients in the ORR, PFS, and OS analyses, respectively, after exclusions. ORR difference did not reach statistical significance between patients with less than 3 months versus 3–6 months versus more than 6 months to 2L ICI. However, PFS (HR 1.64; 95% CI 1.02–2.63) and OS (HR 1.77; 95% CI 1.10–2.84) was shorter among those with time to 2L ICI less than 3 months compared to those who initiated 2L ICI more than 6 months. CONCLUSION: Among patients with aUC treated with 2L ICI, time to 2L ICI less than 3 months was associated with lower, but not significantly different ORR, but shorter PFS and OS compared to 2L ICI more than 6 months. This highlights potential cross resistance mechanisms between ICI and platinum-based chemotherapy.

Objectives: To compare clinical outcomes between patients with locally advanced (unresectable) or metastatic urothelial carcinoma (aUC) in the upper and lower urinary tract receiving immune checkpoint inhibitors (ICIs). Patients and methods: We performed a retrospective cohort study collecting clinicopathological, treatment, and outcome data for patients with aUC receiving ICIs from 2013 to 2020 across 24 institutions. We compared the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) between patients with upper and lower tract UC (UTUC, LTUC). Uni- and multivariable logistic and Cox regression were used to assess the effect of UTUC on ORR, OS, and PFS. Subgroup analyses were performed stratified based on histology (pure, mixed) and line of treatment (first line, subsequent line). Results: Out of a total of 746 eligible patients, 707, 717, and 738 were included in the ORR, OS, and PFS analyses, respectively. Our results did not contradict the hypothesis that patients with UTUC and LTUC had similar ORRs (24% vs 28% ; adjusted odds ratio [aOR] 0.73, 95% confidence interval [CI] 0.43-1.24), OS (median 9.8 vs 9.6 months ; adjusted hazard ratio [aHR] 0.93, 95% CI 0.73- 1.19), and PFS (median 4.3 vs 4.1 months ; aHR 1.01, 95% CI 0.81-1.27). Patients with mixed- histology UTUC had a significantly lower ORR and shorter PFS vs mixed-histology LTUC (aOR 0.20, 95% CI 0.05-0.91 and aHR 1.66, 95% CI 1.06-2.59), respectively). Conclusion: Overall, patients with UTUC and LTUC receiving ICIs have comparable treatment response and outcomes. Subgroup analyses based on histology showed that those with mixed- histology UTUC had a lower ORR and shorter PFS compared to mixed-histology LTUC. Further studies and evaluation of molecular biomarkers can help refine patient selection for immunotherapy.

PURPOSE: Aggressive care at the end of life (EOL) can lead to unnecessary suffering and health care costs for patients with cancer. Despite geographic proximity and cultural similarities, we hypothesize that EOL care is more intense in the United States multipayer system versus the Canadian single-payer system. We compared health care utilization at EOL among patients with cancer in Alberta, Canada, with those in Washington state in the United States. METHODS: Adult patients with American Joint Committee on Cancer stage II to IV solid tumors who died between 2014 and 2016 in Alberta and between 2015 and 2017 in Washington were identified from regional population-based cancer registries linked to treatment and hospitalization records (Alberta) and health claims from major regional insurance plans (Washington). The proportion of patients receiving chemotherapy and having multiple emergency department (ED) visits, or intensive care unit (ICU) admissions in the last 30, 60, and 90 days of life (DOL) in Alberta and Washington were determined and compared using two-sample z-test and multivariable logistic regression (α = .006 after Bonferroni correction). RESULTS: Of patients, 11,177 in Alberta and 12,807 in Washington were included. Patients were similar in age (median, 71 v 72 year), with more patients in Washington with no comorbidities. More patients in Washington were treated with chemotherapy (12.6% v 6.6%; adjusted OR [aOR], 2.74), had multiple ED visits (16.2% v 12.1%; aOR, 1.40), and ICU admissions (23.7% v 3.9%; aOR, 14.27) in the last 30 DOL. Utilization was also higher in Washington in the last 60 and 90 DOL and among those with stage IV disease and those age 65 years and older. CONCLUSION: Utilization of chemotherapy, ED visits, and ICU admissions near EOL was higher in Washington versus Alberta. Future studies to characterize drivers of aggressive EOL care may help improve cancer care for patients in the United States and Canada.

Ensuring patients have access to safe and efficacious medicines in a timely manner is an essential goal for regulatory agencies, one which has particular importance in oncology because of the substantial unmet need for new therapies. The 2 largest regulatory agencies, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have pivotal global roles, and their recommendations and approvals are frequently followed by other national regulators.To compare market authorization dates for new oncology therapies approved in the US and Europe over the past decade and to examine and contrast the regulatory activities of the FDA and EMA in the approval of new cancer medicines.This cross-sectional study reviewed the FDA and EMA regulatory databases to identify new oncology therapies approved in both the US and Europe from 2010 to 2019, and characterization of the timings of regulatory activities. Statistical analysis was performed from January to April 2022.Regulatory approval date, review time, submission of market authorization application, accelerated approval or conditional marketing authorization status and proportion of approvals prior to peer-reviewed publication of pivotal trial results.In total, 89 new concomitant oncology therapies were approved in the US and Europe from 2010 to 2019. The FDA approved 85 oncology therapies (95%) before European authorization and 4 therapies (5%) after. The median (IQR) delay in market authorization for new oncology therapies in Europe was 241 (150-370) days compared with the US. The median (IQR) review time was 200 (155-277) days for the FDA and 426 (358-480) days for the EMA. Sixty-four new licensing applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA. Thirty-five oncology therapies (39%) were approved by the FDA prior to pivotal study publication, whereas only 8 (9%) by the EMA.In this cross-sectional study, new oncology therapies were approved earlier in the US than Europe. The FDA received licensing applications sooner and had shorter review times. However, more therapies were approved prior to licensing study publication, leaving uncertainty for practitioners regarding clinical utility and safety of newly approved therapies.

Background: Immune checkpoint inhibitors (ICI) improve overall survival (OS) in patients with locally advanced, unresectable, or metastatic urothelial carcinoma (aUC), but response rates can be modest. We compared outcomes between patients with and without prior intravesical Bacillus Calmette-Guerin (BCG), who received ICI for aUC, hypothesizing that prior intravesical BCG would be associated with worse outcomes. Patients and methods: We performed a retrospective cohort study across 25 institutions in US and Europe. We compared observed response rate (ORR) using logistic regression ; progression-free survival (PFS) and OS using Kaplan-Meier and Cox proportional hazards. Analyses were stratified by treatment line (first line/salvage) and included multivariable models adjusting for known prognostic factors. Results: A total of 1026 patients with aUC were identified ; 614, 617, and 638 were included in ORR, OS, PFS analyses, respectively. Overall, 150 pts had history of prior intravesical BCG treatment. ORR to ICI was similar between those with and without prior intravesical BCG exposure in both first line and salvage settings (adjusted odds radios 0.55 [P= .08] and 1.65 [P= .12]). OS (adjusted hazard ratios 1.05 [P= .79] and 1.13 [P= .49]) and PFS (adjusted hazard ratios 1.12 [P= .55] and 0.87 [P= .39]) were similar between those with and without intravesical BCG exposure in first line and salvage settings. Conclusion: Prior intravesical BCG was not associated with differences in response and survival in patients with aUC treated with ICI. Limitations include retrospective nature, lack of randomization, presence of selection and confounding biases. This study provides important preliminary data that prior intravesical BCG exposure may not impact ICI efficacy in aUC.

Introduction: Hospitalized patients with COVID-19 may have increased risk of venous thromboembolism (VTE) and pulmonary embolism (PE). Cancer and anti-cancer therapies are well-known additional risk factors for VTE. Nonetheless, the VTE risk in patients with both cancer and COVID-19 infection remains unknown as recent studies have not found an association due to sample size limitations. We report the incidence of and risk factors for VTE and PE among hospitalized patients with cancer and COVID-19. Methods: The COVID-19 and Cancer Consortium (CCC19) developed an international retrospective cohort study (NCT04354701) to investigate the clinical course and complications of COVID-19 among adult patients with an active or previous history of cancer. For the current study, cumulative incidences of clinically detected VTE and PE were analyzed among hospitalized patients with laboratory confirmed SARS-CoV-2. Pre-specified subgroup analysis was performed to examine the interaction between intensive care unit (ICU) admission and recent anti-cancer therapy on VTE outcomes. Bivariable logistic regression analyses were conducted to assess the association between baseline variables and VTE; unadjusted odds ratios (OR) and 95% confidence interval (CI) were reported. These variables included age, sex, obesity (BMI>30), race/ethnicity, performance status, comorbidities, blood type, history of VTE, recent surgery, recent anti-cancer therapy, cancer subtype VTE risk grouping (adapted from Khorana Score), pre-admission anticoagulant or antiplatelet use, and ICU admission status. Results: From March 17, 2020 to July 31, 2020, 3914 patients were enrolled in the CCC19 registry. For the present analysis, patients were excluded if they had inadequate follow-up The overall incidence of inhospital VTE and PE was 9.3% and 5.2%, respectively. The corresponding estimates were 13.4% and 7.9% among the ICU subgroup. On bivariable analysis, significant predictors of VTE included ICU admission, recent anti-cancer therapy, active cancer status, cancer subtype VTE risk grouping, and pre-admission antiplatelet use (Table 1). Pre-admission anticoagulant use had significant associations with PE but not VTE. Multivariable adjustment is ongoing to identify independent risk factor for VTE and clarify the impact of pre-admission anticoagulant/antiplatelet use controlled for other potential confounders. Both ICU admission status and anti-cancer therapy increased the risk of VTE independently. Non-ICU patients not on anti-cancer therapy had the lowest incidence of VTE (4.5%), whose estimate was similar to that reported in the non-cancer hospitalized population with COVID-19 infection. Patients with either ICU admission or recent anti-cancer therapy had the intermediate risk (11.0%), whereas ICU patients with recent anti-cancer therapy had the highest risk (16.7%). We did not observe confounding or effect modification by the ICU subgroup on the association between anti-cancer therapy and VTE. Conclusion: In this cohort study of hospitalized patients with cancer and COVID-19, recent anti-cancer therapy, active disease, high-risk VTE cancer subtypes, and ICU admission have increased risk of VTE and PE, while pre-admission anticoagulant/antiplatelet therapy may reduce the risk. This information will aid in developing a risk prediction tool for VTE in hospitalized patients with cancer and COVID-19. Disclosures Kuderer: G1 Therapeutics: Consultancy; Total Health: Consultancy; Invitae: Consultancy; Beyond Springs: Consultancy; Bristol-Myers Squibb: Consultancy; celldex: Consultancy; Bayer: Consultancy; Spectrum Pharmaceuticals: Consultancy; Janssen: Consultancy. Warner:HemOnc.orgLLC: Other: Shareholder/Stockholder/Stock options; IBM Watson Health: Consultancy; Westat: Consultancy; National Cancer Institute: Research Funding. Shah:American Cancer Society and the Hope Foundation for Cancer Research: Research Funding; National Cancer Institute: Research Funding. Zon:Amagma Therapeutics.: Consultancy, Other: stockholder. Shah:Aspen Pharma: Research Funding. Gulati:Puma Biotechnology: Consultancy; AstraZeneca: Research Funding; Isoray: Research Funding. Khaki:Merck: Other: share/stockholder; Pfizer: Other: share/stockholder. Thompson:AIM Specialty Health, BMS, GlaxoSmithKline, Takeda, Via Oncology: Membership on an entity's Board of Directors or advisory committees; Synapse Precision Medical Council: Other: Travel expenses; Doximity: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Grivas:Oncogenex: Research Funding; Immunomedics: Research Funding; Debiopharm: Research Funding; Bavarian Nordic,: Research Funding; QED Therapeutics: Honoraria; Seattle Genetics: Honoraria; Roche: Honoraria; Pfizer: Honoraria, Research Funding; Mirati Therapeutics: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Janssen: Honoraria; Heron Therapeutics: Honoraria; GlaxoSmithKline: Honoraria; Genzyme: Honoraria; Genentech: Honoraria, Research Funding; Foundation Medicine: Honoraria; Exelixis: Honoraria; EMD Serono: Honoraria; Driver: Honoraria; Clovis Oncology: Honoraria, Research Funding; Bristol-Myers Squibb,: Consultancy, Honoraria, Research Funding, Speakers Bureau; Biocept: Honoraria; Bayer: Honoraria, Research Funding; Astra Zeneca: Honoraria, Research Funding. de Lima Lopes:Bavarian Nordic: Research Funding; NOVARTIS: Research Funding; Tesaro: Research Funding; GSK: Research Funding; G1 Therapeutics: Research Funding; adaptimmune: Research Funding; BMS: Research Funding; Lilly: Research Funding; Merck Sharp & Dohme: Research Funding; Astra Zeneca: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Boehringer Ingelheim: Honoraria; Janssen: Research Funding; rgenix: Research Funding; Blueprint Medicines: Research Funding; Genentech: Research Funding; Roche: Research Funding; EMD Serono: Research Funding. Shyr:Roche: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Johnson & Johnson: Consultancy; GlaxoSmithKline: Consultancy; AstraZeneca: Consultancy, Speakers Bureau; Boehringer Ingelheim: Speakers Bureau; Eisai: Speakers Bureau. Pennell:Merck: Consultancy; Cota: Consultancy; Inivata: Consultancy; G1 Therapeutics: Consultancy; Astrazeneca: Consultancy; BMS: Consultancy; Eli Lilly: Consultancy; Amgen: Consultancy; Genentech: Consultancy. Friese:Eli Lilly: Consultancy; Patient-Centered Outcomes Research Institute: Membership on an entity's Board of Directors or advisory committees; Agency for Healthcare Research and Quality: Research Funding; National Cancer Institute: Research Funding; Merck Foundation: Research Funding; National Comprehensive Cancer Network: Research Funding; Pfizer: Research Funding; Eli Lilly: Consultancy. Patel:reast Cancer Research Foundation: Research Funding; Sanofi: Research Funding; Odonate Therapeutics: Research Funding; Radius: Honoraria; Genentech: Research Funding. Halmos:Foundation Medicine: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Guardant Health: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Boehringer-Ingelheim: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Eli-Lilly: Research Funding; Advaxis: Research Funding; Mirati: Research Funding; Takeda: Research Funding; GSK: Research Funding; AbbVie: Research Funding; Genentech: Consultancy; TPT: Consultancy. Choueiri:Pfizer: Consultancy, Honoraria, Research Funding; Pionyr: Consultancy, Other; Merck: Consultancy, Honoraria, Research Funding; Roche Products Limited: Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche: Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Lilly: Consultancy, Research Funding; Peloton: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Tempest: Consultancy, Other; Lilly Ventures: Consultancy; International Patent Application No. PCT/US2018/12209, entitled "PBRM1 Biomarkers Predictive of Anti-Immune Checkpoint Response," filed January 3, 2018, claiming priority to U.S. Provisional Patent Application No. 62/445,094, filed January 11, 2017: Patents & Royalties; Prometheus Labs: Consultancy, Honoraria, Research Funding; Corvus: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Bristol Myers-Squibb/ER Squibb and sons LLC: Consultancy, Honoraria, Research Funding; Cerulean: Consultancy, Honoraria, Research Funding; Eisai: Consultancy, Honoraria, Research Funding; oundation Medicine Inc.: Consultancy, Honoraria, Research Funding; International Patent Application No. PCT/US2018/058430, entitled "Biomarkers of Clinical Response and Benefit to Immune Checkpoint Inhibitor Therapy," filed October 31, 2018, claiming priority to U.S. Provisional Patent Application No. 62/581,175, filed N: Patents & Royalties; Calithera: Research Funding; Analysis Group: Research Funding; Sanofi/Aventis: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; EMD Serono: Consultancy, Honoraria; Up-to-Date: Consultancy, Honoraria; NCCN: Consultancy, Honoraria; Lilly Oncology: Consultancy, Honoraria; Heron Therapeutics: Consultancy, Honoraria; Lancet Oncology: Honoraria; NEJM: Honoraria; American Society of Medical Oncology: Honoraria; Harborside Press: Honoraria; Navinata Healthcare: Honoraria; Platform Q: Honoraria; L-path, Kidney Cancer Journal, Clinical Care Options: Honoraria; Research to Practice: Honoraria; PeerView and PER: Honoraria; OnClive: Honoraria; Genentech: Consultancy, Honoraria, Research Funding; Ipsen: Consultancy, Honoraria, Research Funding; Tracon: Research Funding; Exelixis: Consultancy, Honoraria, Research Funding; Analysis Group: Consultancy, Honoraria; Michael J. Hennessy (MJH) Associates, Inc: Honoraria. Peters:Debiopharm: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria; Blueprint Medicines: Consultancy, Honoraria; Bioinvent: Consultancy, Honoraria; Biocartis: Consultancy, Honoraria; Eli Lilly: Consultancy, Honoraria; F. Hoffmann-La Roche: Consultancy, Honoraria, Research Funding; Foundation Medicine: Consultancy, Honoraria; Illumina: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Merck Sharp and Dohme: Consultancy, Honoraria, Research Funding; Merck Serono: Consultancy, Honoraria, Research Funding; Merrimack: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Pharma Mar: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Regeneron: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Vaccibody: Consultancy, Honoraria; Biodesix: Research Funding; Daiichi Sankyo: Consultancy, Honoraria; Clovis: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Painter:Roche: Other: stock or other ownership; OPKO Health Inc: Other: stock or other ownership; Inovio: Other: stock or other ownership; Epizyme: Other: stock or other ownership; Pfizer: Other: stock or other ownership. Rini:Astra-Zeneca: Research Funding; PTC Therapeutics: Other: Sotckholder/stock options; Surface Oncology: Consultancy; Synthorx: Consultancy; 3D Medicine: Consultancy; Arravive: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; AVEO: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Merck: Consultancy, Research Funding. Lyman:Amgen: Research Funding; Mylan: Consultancy; Beyond Spring: Consultancy; Samsung: Consultancy; Sandoz: Consultancy; Invitae: Consultancy; Spectrum: Consultancy; G1 Therapeutics: Consultancy. Connors:Bristol-Myers Squibb: Consultancy, Honoraria; Portola: Honoraria; CSL Behring: Research Funding; Takeda: Honoraria; Abbott: Consultancy, Honoraria. Rosovsky:Bristol-Myers Squibb: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Dova: Consultancy; Portola: Consultancy.

Gender parity within academic oncology is important. We hypothesized that gender differences exist in subspecialty choice and academic rank among medical oncologists. We performed a cross-sectional study of adult medical oncologists at the top 15 cancer centers. Gender, rank, subspecialty (breast, thoracic, gastrointestinal, and genitourinary) and board certification year were recorded. 570 medical oncologists were identified (60% men; 40% women). More women practice breast oncology (OR 3.1, p

In a large observational study in patients with COVID-19 and cancer, survival was not significantly influenced by receipt of COVID-19 treatments, except hydroxychloroquine plus any other treatment, which was associated with reduced survival., Among 2,186 U.S. adults with invasive cancer and laboratory-confirmed SARS-CoV-2 infection, we examined the association of COVID-19 treatments with 30-day all-cause mortality and factors associated with treatment. Logistic regression with multiple adjustments (e.g., comorbidities, cancer status, baseline COVID-19 severity) was performed. Hydroxychloroquine with any other drug was associated with increased mortality versus treatment with any COVID-19 treatment other than hydroxychloroquine or untreated controls; this association was not present with hydroxychloroquine alone. Remdesivir had numerically reduced mortality versus untreated controls that did not reach statistical significance. Baseline COVID-19 severity was strongly associated with receipt of any treatment. Black patients were approximately half as likely to receive remdesivir as white patients. Although observational studies can be limited by potential unmeasured confounding, our findings add to the emerging understanding of patterns of care for patients with cancer and COVID-19 and support evaluation of emerging treatments through inclusive prospective controlled trials. Significance: Evaluating the potential role of COVID-19 treatments in patients with cancer in a large observational study, there was no statistically significant 30-day all-cause mortality benefit with hydroxychloroquine or high-dose corticosteroids alone or in combination; remdesivir showed potential benefit. Treatment receipt reflects clinical decision-making and suggests disparities in medication access. This article is highlighted in the In This Issue feature, p. 1426

LAY SUMMARY Despite longer survival with immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1), metastatic urothelial carcinoma remains lethal. There is an unmet need to further improve the efficacy of these agents. In their phase 2 trial, Zhang et al. evaluated the combination of pembrolizumab (a PD-1 inhibitor) plus acalabrutinib (a novel agent inhibiting an enzyme considered relevant to immunotherapy resistance) based on strong rationale but did not demonstrate clinical benefit compared with pembrolizumab alone. Future trials that examine such promising rational combinations may be able to evaluate selected patients based on validated biomarkers to optimize benefit in an endless pursuit of personalizing therapies.

Urinary tract cancer can be pure urothelial carcinoma, pure nonurothelial carcinoma or variant urothelial carcinoma (defined here as mixed urothelial carcinoma). Little is known regarding outcomes for patients with variant urothelial carcinoma receiving immune checkpoint inhibitors. We hypothesized that variant urothelial carcinoma does not compromise immune checkpoint inhibitor efficacy in patients with advanced urothelial carcinoma.We performed a retrospective cohort study across 18 institutions. Demographic, clinicopathological, treatment and outcomes data were collected for patients with advanced urothelial carcinoma who received immune checkpoint inhibitors. Patients were divided into pure vs variant urothelial carcinoma subgroups, with variant urothelial carcinoma further divided by type of variant (ie squamous, neuroendocrine etc). We compared overall response rate using univariate and multivariate logistic regression and progression-free survival and overall survival using Kaplan-Meier and univariate and multivariate Cox proportional hazards.Overall 519 patients were identified, with 395, 406 and 403 included in overall response rate, overall survival and progression-free survival analyses, respectively. Overall response rate to immune checkpoint inhibitors between patients with pure vs variant urothelial carcinoma was comparable (28% vs 29%, p=0.90) without significant differences for individual subtypes vs pure urothelial carcinoma. Median overall survival for patients with pure urothelial carcinoma was 11.0 months vs 10.1 months for variant urothelial carcinoma (p=0.60), but only 4.6 months for patients with neuroendocrine features (9 patients, HR 2.75, 95% CI 1.40-5.40 vs pure urothelial carcinoma, p=0.003). Median progression-free survival was 4.1 months for pure vs 5.2 months for variant urothelial carcinoma (p=0.43) and 3.7 months for neuroendocrine features (HR 1.87, 95% CI 0.92-3.79 vs pure urothelial carcinoma, p=0.09).Overall response rate to immune checkpoint inhibitors was comparable across histological types. However, overall survival was worse for patients with tumors containing neuroendocrine features. Variant urothelial carcinoma should not exclude patients from receiving immune checkpoint inhibitors.

Summary Background Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness. Methods In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. Findings Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57–76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53–2·21), male sex (1·63, 1·07–2·48), smoking status (former smoker vs never smoked: 1·60, 1·03–2·47), number of comorbidities (two vs none: 4·50, 1·33–15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11–7·18), active cancer (progressing vs remission: 5·20, 2·77–9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79–4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07–0·84) or the US-Midwest (0·50, 0·28–0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. Interpretation Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments. Funding American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.

Introduction Central nervous system (CNS) metastasis in patients with urothelial carcinoma (UC) is uncommon and poorly understood. We aimed to explore the clinical behavior and outcomes of this unique patient population. Materials and Methods We performed a retrospective analysis of patients with UC and CNS metastasis, treated in our institution (2006-2018), along with an exploratory patient-point meta-analysis of a similar patient population derived from a comprehensive literature review. Data regarding diagnosis, management, and outcomes were extracted. Overall survival, time to CNS metastasis (TTCM), and residual survival (RS) from CNS involvement to death were calculated (Kaplan–Meier method). Cox regression was used for testing key clinicopathologic associations. Results We identified 20 “institutional” and 154 “literature” patients with adequate data granularity for analysis. Median TTCM was 17.7 (institutional cohort) and 10 (literature cohort) months. Most patients who developed CNS metastases had previous non-CNS metastasis (15/20 [75%] and 103/154 [67%], respectively). CNS lesions without previous history of metastasis were identified in 5/20 (25%) and 33/154 (21%) cases and those patients had a shorter TTCM. CNS lesions in the absence of known UC history were also documented in 18/154 (12%) literature cases. Multifocal CNS disease was associated with shorter RS in both cohorts in univariate, but not multivariate, analysis. Conclusion We observed a variability in disease presentation and course, with a subset of patients showing an early predilection for CNS insult, potentially reflecting a diverse underlying biology. Genomic profiling studies, elucidating the molecular landscape, and driving future treatments should be considered in this setting.

BACKGROUND: Plasmacytoid urothelial carcinoma is a rare bladder cancer variant with scarce data on outcomes and prognostic factors. OBJECTIVE: We report our institutional experience with this histology to determine response to neoadjuvant chemotherapy, definitive surgery and survival. METHODS: We conducted a retrospective chart review of consecutive patients with plasmacytoid, as well as conventional urothelial carcinoma (for comparison) seen in our institution (2007– 2018). Baseline characteristics, clinicopathologic and treatment data were captured. T-test, chi-squared and log-rank test was used for group comparison. Kaplan Meier method was used for estimation of overall survival and Cox regression for identification of prognostic factors. RESULTS: 64 patients with plasmacytoid and 418 with conventional urothelial histology were identified; 53% of those with plasmacytoid presented with cT3/4 stage and 67% underwent extirpative surgery. Patients with plasmacytoid histology had higher rates of pT3/4 (65% vs. 28%), nodal disease (37% vs. 16%) and positive surgical margins (23% vs. 5%) compared to urothelial group (p

Older age is associated with poorer outcomes of SARS-CoV-2 infection, although the heterogeneity of ageing results in some older adults being at greater risk than others. The objective of this study was to quantify the association of a novel geriatric risk index, comprising age, modified Charlson comorbidity index, and Eastern Cooperative Oncology Group performance status, with COVID-19 severity and 30-day mortality among older adults with cancer.In this cohort study, we enrolled patients aged 60 years and older with a current or previous cancer diagnosis (excluding those with non-invasive cancers and premalignant or non-malignant conditions) and a current or previous laboratory-confirmed COVID-19 diagnosis who reported to the COVID-19 and Cancer Consortium (CCC19) multinational, multicentre, registry between March 17, 2020, and June 6, 2021. Patients were also excluded for unknown age, missing data resulting in unknown geriatric risk measure, inadequate data quality, or incomplete follow-up resulting in unknown COVID-19 severity. The exposure of interest was the CCC19 geriatric risk index. The primary outcome was COVID-19 severity and the secondary outcome was 30-day all-cause mortality; both were assessed in the full dataset. Adjusted odds ratios (ORs) and 95% CIs were estimated from ordinal and binary logistic regression models.5671 patients with cancer and COVID-19 were included in the analysis. Median follow-up time was 56 days (IQR 22-120), and median age was 72 years (IQR 66-79). The CCC19 geriatric risk index identified 2365 (41·7%) patients as standard risk, 2217 (39·1%) patients as intermediate risk, and 1089 (19·2%) as high risk. 36 (0·6%) patients were excluded due to non-calculable geriatric risk index. Compared with standard-risk patients, high-risk patients had significantly higher COVID-19 severity (adjusted OR 7·24; 95% CI 6·20-8·45). 920 (16·2%) of 5671 patients died within 30 days of a COVID-19 diagnosis, including 161 (6·8%) of 2365 standard-risk patients, 409 (18·5%) of 2217 intermediate-risk patients, and 350 (32·1%) of 1089 high-risk patients. High-risk patients had higher adjusted odds of 30-day mortality (adjusted OR 10·7; 95% CI 8·54-13·5) than standard-risk patients.The CCC19 geriatric risk index was strongly associated with COVID-19 severity and 30-day mortality. Our CCC19 geriatric risk index, based on readily available clinical factors, might provide clinicians with an easy-to-use risk stratification method to identify older adults most at risk for severe COVID-19 as well as mortality.US National Institutes of Health National Cancer Institute Cancer Center.

478 Background: Erdafitinib is FDA-approved for patients (pts) with advanced urothelial carcinoma (aUC) with FGFR2/3 mutation or fusion and progression after platinum-based chemotherapy. It is postulated that FGFR3-altered aUC may be a “cold tumor” and associated with non-T cell-inflamed phenotype and, thus, may be less responsive to ICI. We hypothesized that pts with aUC that harbor FGFR2/3 alterations would have lower response and shorter survival on ICI. Methods: We performed a retrospective cohort study of pts with aUC treated with ICI and available genomic data in 11 institutions; pts with pure non-UC, treated with combinations or on clinical trial were excluded. Outcomes (overall response rate [ORR], progression free survival [PFS] and overall survival [OS] were compared in pts with and without FGFR2/3 alterations. PFS and OS was compared using Cox proportional hazards. All analyses were performed in the overall population and also categorized by treatment line (1st line [1L] vs salvage [2+L]). Multivariable models were adjusted for an internally developed risk score for 1L and Bellmunt risk score for 2+L; p

472 Background: PBC followed by avelumab switch maintenance in non-progressors is the standard first line (1L) aUC treatment. We describe clinical features and outcomes in a ‘real-world’ cohort treated with avelumab maintenance for aUC. We hypothesized that outcomes would be similar with JavelinBladder100 trial data. Methods: This was a retrospective cohort study of pts from 12 sites who received 1L switch maintenance avelumab after no progression to PBC for aUC. We calculated overall response rate (ORR), median overall and progression-free survival (mOS, mPFS) using Kaplan Meier method from avelumab start. We also described OS and PFS for specific subsets using Cox regression. Results: We found 77 pts with aUC (78% pure, 22% mixed UC) with median age 68, 81% men, 91% White, 17% upper tract primary, 66% prior cisplatin, 17% liver metastasis (mets), 80% ECOG PS 0-1 at time of PBC start. There was a median of 6 weeks (range 1-30) from end of PBC to avelumab start; median follow-up time from avelumab start was 22 months (95%CI 16-24). ORR with avelumab maintenance: 28% (complete response [CR] 17%, partial response [PR] 11%), stable disease (SD) 32%; progression as best response 30% (10% unknown); mPFS 7 months (95%CI 5-9), mOS 22 months (95%CI 16-NR). Table shows HR for OS and PFS for specific subsets. Absence (vs presence) of liver mets (p=0.04), ECOG PS 0-1 (vs >1; p=0.01) and CR/PR (vs SD) to 1L PBC (p=0.03) were associated with longer OS. Conclusions:‘Real world’ outcomes with avelumab maintenance in pts with aUC align with JavelinBladder100 trial data (but higher ORR). Good PS, response to PBC and absence of liver mets are favorable prognostic factors. Limitations include moderate sample size, retrospective design, lack of randomization and central scan review, possible selection and confounding biases. Other studies (e.g. PATRIOT-II) can generate more data in pts on maintenance avelumab outside clinical trials. [Table: see text]

524 Background: The immune-responsive nature of bladder cancer has made it an active area of interest for novel applications of immune checkpoint inhibitors (ICIs), with multiple ICI agents approved in the metastatic setting and ongoing perioperative trials. Variant histology urothelial carcinoma is a rare, heterogenous, and aggressive disease category associated with poor prognosis and response to standard therapies. This investigator-initiated phase 2 trial explored the addition of durvalumab to neoadjuvant chemotherapy (NAC) in the setting of variant histology MIBC. Methods: Patients with cT2-T4a, N0-N1, M0 histologically-confirmed bladder cancer of variant histology who were candidates for platinum-based NAC and radical cystectomy were eligible for the study. Enrolled patients received durvalumab with each cycle of investigator’s choice of platinum NAC (ddMVAC, cisplatin/gemcitabine, or carboplatin/gemcitabine). The primary objective was to determine the safety and tolerability of each study treatment as assessed by the total number of adverse events of grade 3 or higher, judged by the investigator as probably or definitely related to durvalumab. Secondary objective was to determine the percent of subjects post neoadjuvant chemo immunotherapy who achieve tumor stage of pT2N0M0 or better at cystectomy. Target accrual was 24 patients. Results: Six patients were enrolled (the study closed early due to low accrual). Median age was 72 years, 17% were women, 67% were white, 33% were Asian. 50% received ddMVAC and 50% received carboplatin/gemcitabine. All patients completed the planned cycles of NAC and durvalumab (4 cycles) and 5/6 proceeded to radical cystectomy (one patient declined cystectomy). Three patients experienced a Grade 3 AE that was assessed by the investigator to be related to treatment (table). One patient with sarcomatoid and glandular histology had pathological complete response and one patient with papillary and 10% squamous had pT2N0 at cystectomy. Conclusions: The addition of durvalumab to platinum NAC for patients with variant-histology muscle invasive bladder cancer demonstrates a reasonable safety and tolerability profile. Further investigation into this combination is warranted in larger scale trials. Clinical trial information: NCT03912818 . [Table: see text]

450 Background: EV, an antibody-drug conjugate (ADC) targeting Nectin-4, is used widely in treatment-refractory aUC, but limited data are available on biomarkers predictive of EV outcomes. We investigated potential biomarkers of response to EV in a pt cohort in the UNITE dataset. Methods: We included the retrospective UNITE study pts from 16 sites, with available next generation sequencing using institutional or commercial platforms, treated with EV alone outside clinical trials. Observed response (ORR) was determined by investigators for evaluable pts with scans after ≥1 dose of EV. Assessed molecular biomarkers included tumor mutation burden (TMB), PD-L1 status, somatic alterations (alts) in ≥ 10% of pts ( TERTp, TP53, ARID1A, CDKN2A, CDKN2B, FGFR3, ERBB2, CCND1, KDM6A, MTAP, PIK3CA, RB1, TSC1) and presence of ≥1 DNA damage response mutations ( ATM, BARD1, BRCA1, BRCA2, CDK12, CHEK2, PALB2, PPP2R2A, or RAD51B). ORRs were compared using Chi-squared test, while median progression-free and overall survival (mPFS, mOS) from EV start were compared with log-rank test and Cox proportional hazards in pts with and without biomarker presence. Results: A total of 170 pts had outcomes and NGS data available. Median age was 70, 133 (78%) were men, 144 (85%) Caucasian, 110 (65%) with pure urothelial histology, 118 (69%) with primary bladder tumor, and 116 (68%) had ≥ 2 lines of therapy before EV. For all pts, ORR 47%, mPFS 6 mos, mOS 12 mos. ORRs were higher in pts with ERBB2 (67% vs 44%; p = 0.05) and TSC1 (68% vs 25%; p=0.04) alts vs wild-type. Shorter mPFS was noted in pts with CDKN2A, CDKN2B, and MTAP alts, and longer mOS in pts with high TMB (table). Conclusions: This large, multi-site, retrospective cohort of pts with aUC identified several potential biomarkers associated with differential outcomes to EV. These findings, upon external validation, may help inform clinical decision making and potential therapy sequencing with available ADCs. Limitations include retrospective nature, pt selection, and confounding biases. [Table: see text]

Immune checkpoint inhibitors (ICIs) have already been approved for the treatment of metastatic urothelial carcinoma and are now being investigated for perioperative treatment of muscle-invasive bladder cancer (MIBC). Ongoing trials are assessing ICIs as monotherapy and in combination with other treatments. Early data are promising, and long-term survival data are awaited to confirm the potential of ICIs in MIBC.

Key Points Question Given the higher COVID-19–related mortality rate observed among men than among women, is androgen deprivation therapy associated with decreased rate of 30-day mortality from COVID-19 among patients with prostate cancer? Findings In this cohort study of 1106 patients, no statistically significant difference was found in the rates of all cause 30-day mortality following COVID-19 infection among men with prostate cancer receiving androgen deprivation therapy (15%) vs those not receiving androgen deprivation therapy (14%). Meaning The findings of this cohort study do not support an association between androgen deprivation therapy and 30-day mortality among patients with COVID-19 infection., Importance Androgen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissue-based expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2). Objective To examine whether ADT is associated with a decreased rate of 30-day mortality from SARS-CoV-2 infection among patients with prostate cancer. Design, Setting, and Participants This cohort study analyzed patient data recorded in the COVID-19 and Cancer Consortium registry between March 17, 2020, and February 11, 2021. The consortium maintains a centralized multi-institution registry of patients with a current or past diagnosis of cancer who developed COVID-19. Data were collected and managed using REDCap software hosted at Vanderbilt University Medical Center in Nashville, Tennessee. Initially, 1228 patients aged 18 years or older with prostate cancer listed as their primary malignant neoplasm were included; 122 patients with a second malignant neoplasm, insufficient follow-up, or low-quality data were excluded. Propensity matching was performed using the nearest-neighbor method with a 1:3 ratio of treated units to control units, adjusted for age, body mass index, race and ethnicity, Eastern Cooperative Oncology Group performance status score, smoking status, comorbidities (cardiovascular, pulmonary, kidney disease, and diabetes), cancer status, baseline steroid use, COVID-19 treatment, and presence of metastatic disease. Exposures Androgen deprivation therapy use was defined as prior bilateral orchiectomy or pharmacologic ADT administered within the prior 3 months of presentation with COVID-19. Main Outcomes and Measures The primary outcome was the rate of all-cause 30-day mortality after COVID-19 diagnosis for patients receiving ADT compared with patients not receiving ADT after propensity matching. Results After exclusions, 1106 patients with prostate cancer (before propensity score matching: median age, 73 years [IQR, 65-79 years]; 561 (51%) self-identified as non-Hispanic White) were included for analysis. Of these patients, 477 were included for propensity score matching (169 who received ADT and 308 who did not receive ADT). After propensity matching, there was no significant difference in the primary end point of the rate of all-cause 30-day mortality (OR, 0.77; 95% CI, 0.42-1.42). Conclusions and Relevance Findings from this cohort study suggest that ADT use was not associated with decreased mortality from SARS-CoV-2 infection. However, large ongoing clinical trials will provide further evidence on the role of ADT or other androgen-targeted therapies in reducing COVID-19 infection severity., This cohort study using data from the COVID-19 and Cancer Consortium registry examines whether androgen deprivation therapy is associated with decreased rates of mortality within 30 days of COVID-19 diagnosis among patients with prostate cancer.

Our goal was to identify discrete clinical characteristics associated with safe discharge from an emergency department/urgent care for patients with a history of cancer and concurrent COVID-19 infection during the SARS-CoV-2 pandemic and prior to widespread vaccination.We retrospectively analyzed 255 adult patients with a history of cancer who presented to Memorial Sloan Kettering Cancer Center (MSKCC) urgent care center (UCC) from March 1, 2020 to May 31, 2020 with concurrent COVID-19 infection. We evaluated associations between patient characteristics and 30-day mortality from initial emergency department (ED) or urgent care center (UCC) visit and the absence of a severe event within 30 days. External validation was performed on a retrospective data from 29 patients followed at Fred Hutchinson Cancer Research Center that presented to the local emergency department. A late cohort of 108 additional patients at MSKCC from June 1, 2020 to January 31, 2021 was utilized for further validation.In the MSKCC cohort, 30-day mortality and severe event rate was 15% and 32% respectively. Using stepwise regression analysis, elevated BUN and glucose, anemia, and tachypnea were selected as the main predictors of 30-day mortality. Conversely, normal albumin, BUN, calcium, and glucose, neutrophil-lymphocyte ratio3, lack of (severe) hypoxia, lack of bradycardia or tachypnea, and negative imaging were selected as the main predictors of an uneventful course as defined as a Lack Of a Severe Event within Thirty Days (LOSETD). Utilizing this information, we devised a tool to predict 30-day mortality and LOSETD which achieved an area under the operating curve (AUC) of 79% and 74% respectively. Similar estimates of AUC were obtained in an external validation cohort. A late cohort at MSKCC was consistent with the prior, albeit with a lower AUC.We identified easily obtainable variables that predict 30-day mortality and the absence of a severe event for patients with a history of cancer and concurrent COVID-19. This has been translated into a bedside tool that the clinician may utilize to assist disposition of this group of patients from the emergency department or urgent care setting.

Enfortumab vedotin (EV) is a novel antibody-drug conjugate approved for advanced urothelial cancer (aUC) refractory to prior therapy. In the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) study, the authors looked at the experience with EV in patient subsets of interest for which activity had not been well defined in clinical trials.UNITE was a retrospective study of patients with aUC treated with recently approved agents. This initial analysis focused on patients treated with EV. Patient data were abstracted from chart reviews by investigators at each site. The observed response rate (ORR) was investigator-assessed for patients with at least 1 post-baseline scan or clear evidence of clinical progression. ORRs were compared across subsets of interest for patients treated with EV monotherapy.The initial UNITE analysis included 304 patients from 16 institutions; 260 of these patients were treated with EV monotherapy and included in the analyses. In the monotherapy cohort, the ORR was 52%, and it was40% in all reported subsets of interest, including patients with comorbidities previously excluded from clinical trials (baseline renal impairment, diabetes, and neuropathy) and patients with fibroblast growth factor receptor 3 (FGFR3) alterations. Progression-free survival and overall survival were 6.8 and 14.4 months, respectively. Patients with a pure urothelial histology had a higher ORR than patients with a variant histology component (58% vs 42%; P = .06).In a large retrospective cohort, responses to EV monotherapy were consistent with data previously reported in clinical trials and were also observed in various patient subsets, including patients with variant histology, patients with FGFR3 alterations, and patients previously excluded from clinical trials with an estimated glomerular filtration rate30 mL/min and significant comorbidities.Enfortumab vedotin, approved by the Food and Drug Administration in 2019, is an important new drug for the treatment of patients with advanced bladder cancer. This study looks at the effectiveness of enfortumab vedotin as it has been used at multiple centers since approval, and focuses on important patient populations previously excluded from clinical trials. These populations include patients with decreased kidney function, diabetes, and important mutations. Enfortumab vedotin is effective for treating these patients. Previously reported clinical trial data have been replicated in this real-world setting, and support the use of this drug in broader patient populations.

Background: Patients with sarcoma often require individualized treatment strategies and are likely to receive aggressive immunosuppressive therapies, which may place them at higher risk for severe COVID-19. We aimed to describe demographics, risk factors, and outcomes for patients with sarcoma and COVID-19. Methods: We performed a retrospective cohort study of patients with sarcoma and COVID-19 reported to the COVID-19 and Cancer Consortium (CCC19) registry (NCT04354701) from 17 March 2020 to 30 September 2021. Demographics, sarcoma histologic type, treatments, and COVID-19 outcomes were analyzed. Results: of 281 patients, 49% (n = 139) were hospitalized, 33% (n = 93) received supplemental oxygen, 11% (n = 31) were admitted to the ICU, and 6% (n = 16) received mechanical ventilation. A total of 23 (8%) died within 30 days of COVID-19 diagnosis and 44 (16%) died overall at the time of analysis. When evaluated by sarcoma subtype, patients with bone sarcoma and COVID-19 had a higher mortality rate than patients from a matched SEER cohort (13.5% vs 4.4%). Older age, poor performance status, recent systemic anti-cancer therapy, and lung metastases all contributed to higher COVID-19 severity. Conclusions: Patients with sarcoma have high rates of severe COVID-19 and those with bone sarcoma may have the greatest risk of death.

Background: Xpert MTB/RIF, the most widely used automated nucleic acid amplification test for tuberculosis, is available in more than 130 countries. Although diagnostic accuracy is well documented, anticipated improvements in patient outcomes have not been clearly identified. We performed an individual patient data meta-analysis to examine improvements in patient outcomes associated with Xpert MTB/RIF. Methods: We searched PubMed, Embase, ClinicalTrials.gov, and the Pan African Clinical Trials Registry from inception to Feb 1, 2018, for randomised controlled trials (RCTs) comparing the use of Xpert MTB/RIF with sputum smear microscopy as tests for tuberculosis diagnosis in adults (aged 18 years or older). We excluded studies of patients with extrapulmonary tuberculosis, and studies in which mortality was not assessed. We used a two-stage approach for our primary analysis and a one-stage approach for the sensitivity analysis. To assess the primary outcome of cumulative 6-month all-cause mortality, we first performed logistic regression models (random effects for cluster randomised trials, with robust SEs for multicentre studies) for each trial, and then pooled the odds ratio (OR) estimates by a fixed-effects (inverse variance) or random-effects (Der Simonian Laird) meta-analysis. We adjusted for age and gender, and stratified by HIV status and previous tuberculosis-treatment history. The study protocol has been registered with PROSPERO, number CRD42014013394. Findings: Our search identified 387 studies, of which five RCTs were eligible for analysis. 8567 adult clinic attendees (4490 [63·5%] of 7074 participants for whom data were available were HIV-positive) were tested for tuberculosis with Xpert MTB/RIF (Xpert group) versus sputum smear microscopy (sputum smear group), across five low-income and middle-income countries (South Africa, Brazil, Zimbabwe, Zambia, and Tanzania). The primary outcome (reported in three studies) occurred in 182 (4·5%) of 4050 patients in the Xpert group and 217 (5·3%) of 4093 patients in the smear group (pooled adjusted OR 0·88, 95% CI 0·68–1·14 [p=0·34]; for HIV-positive individuals OR 0·83, 0·65–1·05 [p=0·12]). Kaplan-Meier estimates showed a lower rate of death (12·73 per 100 person-years in the Xpert group vs 16·38 per 100 person-years in the sputum smear group) for HIV-positive patients (hazard ratio 0·76, 95% CI 0·60–0·97; p=0·03). The risk of bias was assessed as reasonable and the statistical heterogeneity across studies was low (I2

Earlier studies on the cost of muscle-invasive bladder cancer treatments are limited to short-term costs of care. We determined the 2- and 5-year costs associated with trimodal therapy (TMT) vs. radical cystectomy (RC).We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Total Medicare costs at 2 and 5 years following RC vs. TMT were compared using inverse probability of treatment-weighted propensity score models.A total of 2,537 patients aged 66 to 85 years were diagnosed with clinical stage T2-4a muscle-invasive bladder cancer. Total median costs for patients that received no definitive treatment(s) were $73,780 and $88,275 at 2-and 5-years. Costs were significantly higher for TMT than RC at 2-years ($372,839 vs. $191,363, Median Difference $127,815, Hodges-Lehmann Estimate (H-L) 95% Confidence Interval (CI), $112,663-$142,966) and 5-years ($424,570 vs. $253,651, Median Difference $124,466, H-L 95% CI, $105,711-$143,221). TMT had higher outpatient costs than RC (2-years: $318,221 vs. $100,900; 5-years: $367,092 vs. $146,561) with significantly higher costs with radiology, medications, pathology/laboratory, and other professional services. RC had higher inpatient costs than TMT (2-years: $62,240 vs. $33,631, Median Difference $-29,174, H-L 95% CI, $-32,364-$-25,984; 5-years: $75,499 vs. $45,223, Median Difference $-29,843, H-L 95% CI, $-33,905-$-25,781).The excess spending associated with trimodal therapy vs. radical cystectomy was largely driven by outpatient expenditures. The relatively high long-term trimodal therapy costs are prime targets for cost containment strategies to optimize future value-based care.

e18815 Background: Disparities in diagnosis, treatment, and outcomes for bladder cancer in underserved patient populations persist in the United States. High out-of-pocket costs can prevent patients from seeking or continuing treatment, which can worsen existing disparities in care. The Association of Community Cancer Centers (ACCC) conducted a claims analysis of Medicare beneficiaries diagnosed with bladder cancer to assess differences in healthcare utilization and costs and to inform future provider education initiatives. Methods: ACCC convened an expert steering committee of multidisciplinary specialists and patient advocates to guide the development of the claims analysis methodology and code sets used to identify study cohorts and model variables. Using the CMS Medicare 100% Innovator Administrative Claims Data Set, incident patients were defined as those newly diagnosed in 2018 using a 24-month lookback to confirm no prior bladder cancer diagnosis. Claims for incident patients incurred in the time-period between 24 months prior to and 24 months following diagnosis date were analyzed to generate descriptive summaries of cohorts by severity of disease at diagnosis. Classification is defined by treatment observed within 6 months of diagnosis: No treatment, Early Stage-treated (intravesical chemotherapy), and Late-stage (one or more claims of non-intravesical systemic therapy, radiation therapy, or major bladder surgery). Results: 4,356 incident patients were identified: average age 77.7, 71% male, 56% no treatment, 15% early-stage treated, 28% late-stage. Patients diagnosed at late-stage incur 128% more allowed costs (total amount paid by Medicare and patients) on all-cause healthcare in the first year after diagnosis than early-stage patients who receive treatment ($76,483 vs $33,530) and 101% higher cumulative costs two years following diagnosis ($112,178 vs $55,814). Patients diagnosed at late-stage incur 90% more out-of-pocket costs (copays, coinsurance, deductibles) in the first year following diagnosis than early-stage treated patients ($9,970 vs $5,225) and 81% higher cumulative out-of-pocket costs two years following diagnosis ($15,145 vs $8,390). For both early- and late-stage patients, the month of diagnosis is the most expensive. 53% of all costs incurred in the month of diagnosis are for cystoscopy/TURBT procedures. Elevated costs persist at levels higher than pre-diagnosis levels for at least 20 months. Among late-stage patients, treatments (surgery, radiation therapy, and systemic therapy) sum to 34% of all costs incurred in 6 months following diagnosis. Conclusions: Patients diagnosed with late-stage bladder cancer experience higher financial burden and need more resource-intensive services than those diagnosed at an earlier stage. Earlier diagnosis of bladder cancer is needed to improve patient outcomes and reduce financial burden.

1524 Background: Excess inpatient mortality is a marker of poor quality in cancer care. We developed a multidisciplinary mortality review committee to review each inpatient death to determine key drivers of mortality and develop targeted interventions to reduce our inpatient mortality index. Methods: Through retrospective review, inpatient deaths were identified at Stanford Health Care for patients with an ICD10 cancer diagnosis regardless of inpatient service. Details of each hospitalization were reviewed by a quality consultant and subsequently reviewed by a physician quality team member to identify opportunities for improvement. Most cases were then discussed in a monthly multidisciplinary committee meeting. The committee analyzed key drivers of inpatient mortality, communicated suggestions to the patient’s outpatient and inpatient attending physicians, and/or identified opportunities for systemic change. The resulting targeted interventions were tracked using the observed versus expected mortality ratio for inpatient deaths over time. Results: From May 2017 through August 2021 we reviewed 528 inpatient oncology deaths. Patients’ median age was 65 years, and the median length of stay was 8 days. 73% of patients had metastatic cancer, and 28% received chemotherapy within 14 days of death. 25% of patients had a prior ED visit, and 35% had a prior hospitalization within 30 days of admission. Only 26% of patients had an advanced directive on record at time of death. Opportunities for improvement were identified for 60% of cases (Table). Interventions have aimed to increase advance care planning conversations and documentation, develop predictive models for cancer-related readmissions and mortality, expand outpatient services for urgent symptoms, and expedite transitions to hospice. Conclusions: Understanding key drivers for preventable inpatient mortality through a multidisciplinary review process identified targeted interventions that have successfully contributed to reduction of the inpatient cancer mortality index.[Table: see text]

e13515 Background: Use of systemic anti-cancer treatment near the end of life (EOL) is recognized as a low value practice with limited benefit to patients. Machine learning (ML) models that identify patients in close proximity to death can help prospectively assess oncology practice of systemic therapy use. We hypothesized that systemic therapy use would be higher based on predicted survival compared with actual survival. Methods: We calculated prevalence of systemic therapy use based on predicted and actual survival among patients with metastatic cancer at Stanford Healthcare from 2008-2019. Patients were included if they were in the test set of the ML model, had an eligible outpatient oncology clinic visit for which a predicted survival was calculated and were deceased . Median predicted survival was calculated from the ML model at each outpatient oncology visit and treatment was linked to a visit date if within 14 days of each other. Prevalence of systemic therapy was calculated for patients with a predicted or actual survival of < 6 months, 6-12 months, 12-18 months and 18-24 months. The five categories of treatment were: chemotherapy, targeted/antibody, hormone, immunotherapy, and other. Results: A total of 951 deceased patients who received anticancer treatment are included and a total of 21,283 doses of treatment were administered with a mean of 22 doses per patient. The median age at metastatic cancer diagnosis was 58 years, 53% of patients were female and most patients identified as White (55%) or Asian (23%). The most common disease groups were gastrointestinal (21.6%), thoracic (18.6%) and breast (14.9%). Overall, the use of different treatment types did not differ based on either predicted or actual survival (Table). In all the survival groupings, chemotherapy remained the predominant medication type, however with a trend of decreasing use with longer predicted and actual survival. Conclusions: The use of cancer medications and the type of medication given did not change based on predicted or actual survival in a large group of patients with metastatic cancer. There was a trend of decreasing chemotherapy use with longer prognosis. Further investigation into use in time intervals closer to (predicted or actual) death and inclusion of those who did not receive any systemic therapy are underway.[Table: see text]