bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment (Rx) trends and attrition with lines of therapy in patients (pts) with advanced urothelial carcinoma (aUC).
Authors: Mathew Thomas Vinay , Jo Yeonjung , Tripathi Nishita , Roy Soumyajit , Chigarira Beverly , Dal Emre , Gebrael Georges , Hage Chehade Chadi , Sayegh Nicolas , Fortuna Gliceida Galarza , Ji Richard , Campbell Patrick , Li Haoran , Agarwal Neeraj , Gupta Sumati , Swami Umang
Published: January 2024

562

Background: The Rx landscape of aUC has evolved significantly with the approval of novel therapeutic agents. However, even with the advent of new therapeutic options, aUC remains a lethal malignancy with poor outcomes. Here, we use a large real-world database to describe Rx trends and attrition in pts with aUC. Methods: Patient data was extracted from the Flatiron Health EHR-derived deidentified database. Inclusion criteria: pts with histological diagnosis of metastatic or aUC between 1/1/11-1/10/2023 and Rx receipt at participating site. Pts receiving Rx for two or more cancers were excluded. Rx were grouped into categories based on NCCN approved regimens. Rx in each line (L) of therapy were summarized using frequency and percentages. All the analysis was done using R version 4.2.3. Results: Of the identified 12,157 pts in the dataset, 8,660 had Rx information and 7,260 were included in the analysis based on eligibility criteria. Details of each line of therapy are presented in the table. Of all pts receiving 1L, only 37% receive 2L and only 12% receive 3L of therapies. Carboplatin containing regimen were most commonly used in 1L followed by PD-1/L1 therapies. PD-1/L1 therapies were most commonly used regimens in 2L and 3L. Over time, there has been a steady decline in the overall use of platinum-based regimens, and since 2015 an increase in uptake of PD-1/L1 agents has been observed. The use of novel therapeutic agents, such as enfortumab vedotin (EV), erdafitinib, and sacituzumab govitecan (SG), has increased since 2019, especially in the 2L and 3L of therapy. Conclusions: Approximately two-thirds of aUC patients don’t receive 2L or beyond systemic therapy. Majority of real-world patients (61%) did not receive cisplatin-based regimens and instead received carboplatin or PD- 1/L1i based therapies. These data warrant the need for more effective and tolerable Rx in front-line setting. [Table: see text]
HER2 mutation and bladder cancer (BC): Prevalence and clinical outcomes.
Authors: Shah Neil J. , Aggen David H , Zheng Junting , Niederhausern Andrew , Alam Syed Muneeb , Balar Om , Bahadur Nadia , Watson Adam , Regazzi Ashley M. , Ratna Neha , Funt Samuel A , Teo Min Yuen , Pietzak Eugene J. , Solit David B. , Bajorin Dean F. , Philip John , Rosenberg Jonathan E. , Ostrovnaya Irina , Al-Ahmadie Hikmat A. , Iyer Gopa
Published: January 2024

574

Background: Novel HER2-directed targeted therapies have revolutionized the treatment paradigm for patients with breast cancer and are being actively investigated in BC. The impact of pathogenic HER2 mutation and/or its amplification on clinical outcomes across various stages of BC is underdefined. Methods: In our retrospective study, we identified 999 BC patients who underwent genetic profiling using MSKCC IMPACT and had at least one year of follow-up. The BC disease states included non-muscle invasive (NMIBC), muscle-invasive (MIBC), and metastatic (MetBC). Patient demographics and HER2 alteration (mutation or amplification) were analyzed and compared closest to the time of IMPACT sampling, using the Kruskal-Wallis rank sum test or the Fisher’s exact test. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS) for MIBC and MetBC, and advanced disease-free survival (ADFS) for NMIBC. The log-rank test and Cox proportional hazard regression were used in survival analyses. Results: The study cohort included NMIBC:359, MIBC:429, and MetBC:211 patients at the time of profiling and the overall incidence of HER2 alteration (mutation or amplification) was 13% (48), 17% (75), and 19% (41), respectively. HER2 Amplification was significantly lower for NMIBC (2.8%) compared to MIBC (9.3%) and MetBC (10%), p<0.001. HER2 S310F and S310Y were the most common pathogenic mutations. Age, race, gender, and smoking status were not associated with the incidence of HER2 alteration for any BC disease states. The median follow-up for NMIBC, MIBC, and MetBC was 5.3, 3.6, and 6.5 years, respectively. HER2 status did not influence ADFS for NMIBC; PFS and OS for MIBC regardless of neoadjuvant cisplatin chemotherapy (chemo); OS for 1st line (1L) MetBC treated with gemcitabine plus platinum (GC) chemo or 2nd line (2L) immune checkpoint inhibitor (ICI) therapy post 1L-chemo (table). Conclusions: We present one of the largest and comprehensive study of HER2 mutation in BC. Overall, HER2 amplification was significantly less frequent for NMIBC. HER2 alterations were not a prognostic marker for NMIBC or MIBC independent of neoadjuvant cisplatin-based chemo, MetBC- 1L GC-chemo and 2L ICI post GC-chemo. Further studies examining IHC and functional HER2 PET imaging are needed to further define the HER2 BC landscape. [Table: see text]
20-year trends in perioperative outcomes in patients with bladder cancer undergoing radical cystectomy with ileal conduit urinary diversion.
Authors: Xu Kevin Lou , Ryu Grace , Makarova Elizaveta , Bakhl Katrina , Boltz Suzanne , Demirsoy Seyma , Raman Jay D. , Truong Hong
Published: January 2024

583

Background: Radical cystectomy is associated with considerable postoperative morbidities. Enhanced recovery after surgery protocol is a multimodal perioperative pathway implemented to improve post-surgical outcomes over the past decade. We sought to compare the 30- and 90-day postoperative morbidity and mortality rates following RC and ileal conduit urinary diversion between 2000-2010 and 2010-2020 to evaluate the trends in patient outcomes and areas that need improvement. Methods: This retrospective cohort study used data from TriNetX US Collaborative network which allowed access to de-identified patient health records from over 43 healthcare organizations. ICD-10 codes were used to identify patients with bladder cancer who underwent radical cystectomy and ileal conduit urinary diversion from 01/01/2000 to 01/01/2020. The rates of 30 and 90-day postoperative morbidities and mortalities were compared between 2000 – 2010 and 2010 – 2020 using the chi-squared test. Results: The 30 and 90-day complications by decade were summarized in Table. There were 738 cases reported from 22 HCOs from 2000 to 2010 and 10,052 cases reported from 43 HCOs from 2010 to 2020. The overall all-cause mortality at 30 and 90-days postop were 1.5% and 4.4%, respectively, and remain unchanged over the past 20 years. The most common complications within 90-days postop were urosepsis (19.1%), acute kidney injury (16.3%), and UTI (15.6%). While most complication rates remain stable, the rates of urosepsis, acute kidney injury, and UTI were higher between 2010 to 2020 compared to 2000 to 2010. Conclusions: Radical cystectomy and urinary diversion procedure is associated with high perioperative morbidities with up to 1 in 5 patients experiencing a complication within 90-days postop. Despite reported improvement in cancer-specific survivals from recent reports, the overall morbidity and mortality rates associated with the procedure have not improved over the past two decades. Further research is needed to improve surgical outcomes, especially in infectious complication and renal function, for patients with bladder cancer undergoing radical cystectomy. [Table: see text]
Characterizing psychological resources and resilience in patients with bladder cancer: Associations with frailty and quality of life.
Authors: Petersen Erin , Holt Sarah K , Browning Anne , Jannat Samia , Cavanaugh Dana , Wright Jonathan L. , Gore John L. , Schade George R. , Psutka Sarah P.
Published: January 2024

585

Background: Bladder cancer (BC) profoundly affects patients’ mental and physical well-being, with significant impacts to quality of life (QOL), mental health, and ability to perform activities of daily living. Understanding factors that influence patients’ responses to BC is crucial to tailored care. One such factor that has yet to be studied in BC patients is resilience, or the ability to maintain or restore baseline function following a stressor. Our objective was to demonstrate the feasibility of prospectively characterizing baseline resilience and frailty in patients with BC. We hypothesized that resilience and psychological resources (PsyResources) would be positively associated with improved QOL and inversely associated with frailty. Methods: With IRB approval, we enrolled patients with BC (N=67) from a urology clinic (6/20-7/2021). Patients completed a comprehensive geriatric assessment incorporating validated assessments of frailty and PsyResources: University of Washington Resilience Survey (UWR), Psychological Capital (PsyCap), Brief Inventory of Thriving (BIT), and Self-Compassion Survey (SCS) which measure resilience, psychological capital, mental health, and self-compassion, respectively. Validated QOL surveys were completed at 2 weeks, 3 and 6 months post-treatment. Correlation matrices evaluated PsyResources’ links with baseline frailty and Spearman’s correlation coefficient (ρ) was reported. Associations between PsyResources, anxiety and depression, and QOL were evaluated with linear regression. Results: The median age of the cohort was 71 (83.6% male) and 77.6% had muscle-invasive BC (cN+:20.9%, M1: 7.6%). PsyResource assessment completion rates ranged 96-100% and had strong inter-assessment associations (ρ=0.52-0.81, p< 0.0001 for all). Baseline PsyResources were strongly inversely correlated with the geriatric depression scale, (ρ=-0.50-0.65, p<0.0001). Negative correlations were found between functional frailty and SCS (ρ=-0.37, p=0.006). A higher baseline of each PsyResource was associated with improved global symptoms, emotional function, and body image (BIT and SCS) (p<0.05) and decreased anxiety and depression over time (B:-0.167 to -2.46; p<0.02). Conclusions: We present the first prospective characterization of baseline PsyResources in patients with BC, revealing positive correlations with mental health and inverse correlations with functional frailty. Interestingly, PsyResources were associated with improved QOL outcomes over time. Ongoing work is exploring the relationship between resilience and different domains of frailty and the potential role of functional recovery and decline following BC treatment. Future work will also evaluate associations with survival outcomes and the ability to modify resilience to facilitate recovery of functional status and quality of life after treatment.
Thromboembolic events associated with neoadjuvant chemotherapy for muscle invasive cancer of the bladder.
Authors: Qureshi Muneeb , Rehan Ahmed , Mok Wai Kit , Salawu Abdulazeez , Goktas Aydin Sabin , Tay Jessica , Hubbard Rachel , Catto James W.F. , Hussain Syed A.
Published: January 2024

586

Background: Patients with muscle invasive bladder cancer who undergo platinum-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy or radiotherapy are at high risk of venous and arterial thromboembolic events (TEE). TEE is associated with delay to radical cancer treatment, significant morbidity and even mortality. This study aimed to document the incidence and characteristics of TEE during NAC and prior to radical treatment. Methods: Retrospective data was collected on all patients in our centre who underwent NAC prior to radical treatment. TEE events were identified based on routine imaging to assess for response to NAC; or imaging based on clinical symptoms developed during (or within 28 days) of NAC but prior to radical treatment. Results: Data was collected on 148 patients between January 2015 and September 2023. Age range: 44 - 82 years, the majority (73.6%) of whom were male. All patients received platinum-based chemotherapy (median 4 cycles). A total of 31 patients (20.9%) developed 35 TEE, including 27 venous events (24 pulmonary emboli and 3 deep venous thromboses), and 8 arterial events (3 aortic thrombus, 4 limb ischaemia, 1 ischemic stroke). Four patients had a venous and arterial TEE. The majority of pulmonary venous TEE were subclinical. Conclusions: Our single-centre study demonstrates that the incidence of TEE during NAC prior to radical treatment for bladder cancer is high. Improved imaging techniques and routine scans post-NAC led to identification of subclinical TEE that require treatment as they are likely to become clinically significant. The high rate of TEE in this patient population is likely to benefit from prophylactic anticoagulation during NAC and should be investigated in future prospective clinical trials.
Clinical outcomes with split-dose cisplatin-based regimens in patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC): Results of a systematic literature review (SLR) and network meta-analysis (NMA).
Authors: O'Dwyer Richard Thomas , Kearney Mairead , Musat Mihaela , Gulas Ioana , Guenther Silke , Hubscher Elizabeth , Moradian Hoora , Sridhar Srikala S.
Published: January 2024

589

Background: Gemcitabine + cisplatin (GC) is one of the most effective and commonly used regimens in la/mUC. In GC, cisplatin is dosed at 70 mg/m2 on day 1 of a 3-week cycle; however, for many pts, impaired renal or cardiac function, neuropathy, or poor performance status can preclude use of cisplatin. A promising alternative is split-dose GC, where the cisplatin dose is divided over 2 days. We conducted an SLR and NMA to better understand outcomes, toxicity, and comparative effectiveness of split-dose GC vs GC, GCarboplatin (GCa), and methotrexate + vinblastine + doxorubicin + cisplatin (MVAC). Methods: An SLR, performed on March 8, 2023, followed Cochrane guidelines to identify observational studies of treated pts with la/mUC and randomized and nonrandomized trials investigating split-dose cisplatin regimens for this indication. No limits were placed on publication year or geography, and studies reported in English, Spanish, French, and German were included. An NMA was conducted for objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results were reported as odds ratios or hazard ratios (HRs) with 95% credible intervals (Crls). Results: Among 120 studies that met SLR inclusion criteria, 16 (6 clinical trials, 10 retrospective studies) conducted in the US, Europe, and Asia published from 1999-2023, representing 1,767 pts, included split-dose GC. Common reasons for choosing split-dose GC were impaired renal function (creatinine clearance ≤60 mL/min), age >70 years, comorbidities, and physician preference. Most often, cisplatin was split (35 mg/m2) on days 1+8 or 1+2, and pts received a median of 3-5 cycles. In studies reporting outcomes with split-dose GC (12 studies), ORRs were 39-80% (11 studies), median PFS was 3.5-9.9 months (7 studies), and median OS was 8.5-18.1 months (11 studies). Discontinuation rates due to adverse events were 8-38% (5 studies). In the NMA, ORR for split-dose GC was significantly higher than GCa but not GC and MVAC. PFS and OS for split-dose GC were not significantly different from GCa, GC, or MVAC (Table). Conclusions: This is the first SLR and NMA of split-dose GC in la/mUC. Despite heterogeneity in the limited studies included, survival with split-dose GC was numerically better than GC and worse versus MVAC but not statistically different in either case. Split-dose GC has the potential to extend the la/mUC population eligible to receive cisplatin-based regimens and warrants further study. [Table: see text]
Effects of perioperative chemotherapy on prognosis in muscle invasive bladder cancer treated with radical cystectomy.
Authors: Hatakeyama Shingo , Taoka Rikiya , Miki Jun , Saito Ryoichi , Fukuokaya Wataru , Matsui Yasuyuki , Kawahara Takashi , Matsuda Ayumu , Kawai Taketo , Kato MInoru , Sazuka Tomokazu , Sano Takeshi , Urabe Fumihiko , Kashima Soki , Naito Hirohito , Murakami Youji , Nishiyama Naotaka , Nishiyama Hiroyuki , Kitamura Hiroshi , Ohyama Chikara ,   The Japanese Urological Oncology Group
Published: January 2024

592

Background: We aimed to evaluate the effect of the number of neoadjuvant chemotherapy (NAC) cycles and the adding adjuvant chemotherapy (AC) after NAC in muscle-invasive bladder cancer (MIBC) on overall survival (OS). Methods: This multicenter retrospective study included 2674 patients with MIBC who underwent radical cystectomy (RC) from 36 institutions within the Japanese Urological Oncology Group. Among them, we selected 1687 patients with cT2-4NxM0 who were treated with RC alone or RC plus perioperative chemotherapy. We compared the effect of the number of NAC cycles (2 vs. ≥3 cycles) and the addition of AC on OS. Cox proportional-hazards regression was used to assess the association of treatment received with OS. Results: Of 1687 patients, 946 were treated with NAC with a median of 3 cycles. Use of NAC significantly prolonged OS compared to the RC alone. The pathological complete response rate was not significantly different between the 2 cycles (22.9%) and ≥3 cycles (27.5%, P = 0.112) groups. OS was not significantly different between the groups (P = 0.559). Multivariable Cox regression analysis showed that pathological high-risk (ypT2–4, pT3–4, or pN+) or cisplatin ineligibility were significantly associated with poor OS, but not the number of NAC cycles (P = 0.238). We identified 942 pathologically high-risk patients after RC who were eligible for AC. We observed no significant OS improvement with addition of AC after NAC as intensive perioperative chemotherapy. The primary limitation is selection bias from confounding by clinical indication. Conclusions: The impact of 3 or more NAC cycles and the addition of AC on OS in MIBC patients treated with RC may be limited.
Bladder-sparing treatment for muscle-invasive bladder carcinoma: A single-center, single-arm clinical study of sequential neoadjuvant chemotherapy followed by tislelizumab neoadjuvant immunotherapy.
Authors: Zeng Yu , Li Changqi , Lv Chengcheng , Fu Cheng , Chen Ang , Fu Shui , Bi Huan , Shan Guangyi , Wang Yiding , Wang Zhe , Liu Qiang , Shao Bo
Published: January 2024

596

Background: Althoughradical cystectomy (RC) in combination with cisplatin-based neoadjuvant chemotherapy is the gold-standard for muscle-invasive bladder carcinoma (MIBC), bladder-sparing treatment have emerged to be an alternative choice for patients who are concerning about the life quality after surgery. The optimal strategy for bladder-sparing treatment such as trimodal therapy (TMT) showed similar effect with RC. Since the TRUCE-01 has illuminated considerable response of neoadjuvant immunotherapy in MIBC, we aim to study whether neoadjuvant chemotherapy plus immunotherapy can improve the bladder-sparing rate in MIBC patients. Methods: 30 planned patients with MIBC (T2-4a N0-1 M0) received cisplatin 70 mg/m2 or carboplatin AUC 4.5 on days 1 every 3 weeks (Q3W) plus gemcitabine 1000 mg/m2 on the 1st and 8th day of each 21-day cycle x 4 cycles. Tislelizumab 200 mg was administered on the 14th day of each 21-day cycle at the 3rd and 4th cycles. CT and cystoscopy imaging were carried out to evaluate disease progression. After the 4th treatment, radical cystectomy, partial cystectomy or TURBT were perform in accordance with the disease status. For continuous bladder-spare treatment, 2 additional cycles of tislelizumab were performed. Bladder-sparing rate was settled as exploratory endpoints based on 2-years follow-up and predictive biomarker will be analyzed. Results: To date, 21 of 30 pts have been enrolled and 17 pts have completed the regimen. 2 pts were excluded because of complicating with other disease (suffering cerebral infraction or rectal cancer during the trail), and 2 pts voluntarily quitted due to intolerance of chemotherapeutic adverse effect (fatigue and gastrointestinal symptoms). 2 pts partially response to the therapy and received RC after disease progression. 1 pt have no response to the therapy and received palliative care as unsuitable for surgery. The resting 10 of 17 pts successfully preserved their bladder by achieving pT0 (58.8%) after treatment. Among them 3 pts have been followed up over 1 year and no relapse was observed. Conclusions: These data support neoadjuvant chemotherapy plus immunotherapy a feasible bladder-sparing choice for patients with MIBC. Further completed follow-up data and biomarker analysis will accurately identify patients who are suitable for this therapy. Clinical trial information: ChiCTR2100050763 .
Remote delivery of cancer genetic testing in veterans with metastatic prostate cancer: A Million Veteran Program study.
Authors: Montgomery Robert Bruce , Lynch Julie Ann , Brown Jessica , Maxwell Kara Noelle , Kabilovic Nismeta , Stoll Katie , Simon Julie , Kogan Maria , Whitbourne Stacey , Gaziano J. Michael , Cheng Heather H. , Etzioni Ruth Douglas , Pritchard Colin C.
Published: January 2024

60

Background: Germline pathogenic alterations are found in approximately 10% of men with metastatic prostate cancer (mPC) and can inform precision therapy, surveillance, and cancer prevention for family. National guidelines recommend germline genetic testing be offered to all men with mPC, yet uptake of testing in the community has been documented to be 6-12% with many barriers to testing. We conducted a study to determine uptake of testing using remote consenting and testing for veterans with mPC who had participated in the Veteran’s Administration Million Veteran Program (MVP). We wanted to know if remote testing could overcome limited point-of-care counseling and ordering to increase uptake of germline testing. Methods: This prospective study enrolled veterans who participated in MVP study with a diagnosis of mPC. Veterans were contacted by mail with an option to opt-out of further contact. Those who did not opt-out were mailed information regarding the study and received a follow-up phone call to establish interest in germline testing with a CLIA-level germline test (BROCA). Those expressing interest provided verbal informed consent and were mailed a saliva collection kit for a multigene cancer predisposition gene panel test (University of Washington). Results were disclosed by phone and mailed to the patient with genetic counseling support and was also sent to the oncology provider by email, phone or both. Two research coordinators and two part-time genetic counselors provided review of consenting, counseling and return of results. Results: As of September 17, 2023, 1952 veterans who were alive with an incident diagnosis of mPC were identified through MVP and did not opt out of further contact. Informational letters were sent to the home address of all eligible participants. 681 (22%) of veterans were reached and completed informed consent. All participants were then sent a saliva kit and 432 (63%) completed testing, with 23 tests currently pending. Among the participants, 70% were White, 21% were Black, 0.5% Asian and 8% unknown. Thirteen percent (53/409) were found to have a germline pathogenic variant. Conclusions: We evaluated uptake of germline testing using a remote, VA system-wide approach to identify and offer genetic testing for veterans with mPC with access and cost issues removed. We completed germline testing at rates significantly higher than those reported in the community with modest personnel requirements, while also reaching a more diverse population of patients. Remote genetic testing can improve uptake of testing in large integrated health care systems.
Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): Long-term outcomes from the JAVELIN Bladder 100 trial in patients (pts) with high body mass index (BMI).
Authors: Aragon-Ching Jeanny B. , Petrylak Daniel P. , Sridhar Srikala S. , Gupta Shilpa , Grivas Petros , Powles Thomas , Gurney Howard , Jacob Natalia , Tyroller Karin , Guenther Silke , Bellmunt Joaquim
Published: January 2024

600

Background: Avelumab 1L maintenance is recommended as standard of care by international treatment guidelines for pts with aUC that has not progressed with 1L platinum-based chemotherapy, based on level 1 evidence from the phase 3 JAVELIN Bladder 100 trial (NCT02603432). In the trial, avelumab 1L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) vs BSC alone (median OS, 23.8 vs 15.0 mo; HR, 0.76 [95% CI, 0.63-0.91]; 2-sided p=0.0036). The long-term safety of avelumab 1L maintenance was also demonstrated. It is estimated that 25% of the world’s population will have BMI ≥30 by 2035, and high BMI is a risk factor for bladder cancer. We report post hoc analyses of long-term outcomes from JAVELIN Bladder 100 in pts with high BMI (≥30) at baseline. Methods: Eligible pts with unresectable locally advanced or metastatic UC without progression after 4-6 cycles of 1L platinum-based chemotherapy were randomized 1:1 to receive avelumab 10 mg/kg every 2 wk + BSC (n=350) or BSC alone (n=350). The primary endpoint was OS; secondary endpoints included PFS and safety. Results: At data cutoff (June 4, 2021), median follow-up was ≥38 mo in both arms. In the avelumab + BSC and BSC alone arms, 67 and 55 pts had high BMI at baseline, respectively. In these pts, median OS was 20.8 mo (95% CI, 16.9-34.4) with avelumab + BSC vs 12.7 mo (95% CI, 8.1-26.6) with BSC alone (HR, 0.77 [95% CI, 0.49-1.21]); 2-y OS rates were 47.8% vs 37.6%, respectively. Median PFS by investigator was 5.6 mo (95% CI, 3.7-7.5) with avelumab + BSC vs 2.1 mo (95% CI, 1.9-4.0) with BSC alone (HR, 0.64 [95% CI, 0.42-0.97]); 2-y PFS rates were 23.5% vs 11.3%, respectively. Long-term safety in pts with high BMI was generally consistent with the overall safety population (Table). Conclusions: This exploratory analysis shows the long-term efficacy and tolerability of avelumab 1L maintenance in pts with high BMI in JAVELIN Bladder 100, with no new safety concerns identified. These results further support the use of avelumab 1L maintenance as standard of care in pts with aUC who are progression free after 1L platinum-based chemotherapy, including pts with high BMI. Clinical trial information: NCT02603432 . [Table: see text]
A retrospective cohort study to monitor real-world safety in patients with locally advanced or metastatic urothelial carcinoma (LA/mUC) treated with sacituzumab govitecan (SG) in the United States.
Authors: Parikh Mamta , Boateng Freda , Eng Susan , Sierecki Mitch , Chen Fangfei , Brockman Jane Michelle , Ghazi Youssef , Ng Leslie
Published: January 2024

608

Background: Patients with LA/mUC experience poor outcomes, with few treatment options historically available. In April 2021, SG (a TROP-2-directed antibody drug conjugate) received accelerated approval for patients with LA/mUC who progressed after platinum-based chemotherapy and immune checkpoint inhibitor therapy, based on the pivotal TROPHY U-01 trial (NCT03547973). We sought to evaluate SG safety in patients with LA/mUC treated in routine clinical practice in this study. Methods: A retrospective cohort of patients aged ≥ 18 years with LA/mUC treated with SG in the United States was evaluated using data from the nationwide Flatiron Health electronic health record–derived de-identified database (from Jan 2011 to Oct 2022). Outcomes included patient characteristics, treatment patterns, adverse events (AEs) of interest incidence, and granulocyte-colony stimulating factor (G-CSF) use. Descriptive statistics were used for data analysis. Results: This study included 86SG-treated patients (male, 70%; median age, 71 [range: 25-85] years; 27% with ECOG ≥ 2; 84% treated in community settings). Most patients (71%) received enfortumab vedotin (EV) in the direct prior line. The majority of patients received SG as monotherapy (94%), with most patients overall (99%) receiving SG as second-line (2L) or later. The most common AEs of interest (any grade, overall) were diarrhea (35%), neutropenia (40%) and nausea/vomiting (21%) (Table). Of the 86 patients, 14 (16%) patients were hospitalized, 8 (9%) discontinued SG treatment likely due to AEs/toxicity, and 3 (3%) died during or within 7 days after the line of treatment. During SG treatment, 52% of patients used G-CSF (primary prophylaxis 24%; secondary prophylaxis 19%; therapeutic use 28%). Only 1 (4.5%) patient who had primary G-CSF prophylaxis developed grade ≥ 3 neutropenia. Conclusions: This study is the largest analysis of SG use in a real-world population with LA/mUC to date; it provides insights into the safety of SG in this setting. Compared with prior data, this real-world population was older, with poorer functionality, and the majority received EV in the direct prior line. Observed AEs were consistent with the known safety profile of SG and indicate that this sequencing is feasible. [Table: see text]
Punch: Preliminary results from a phase II study of intra-arterial chemotherapy (IAC) combined with tislelizumab and bacillus Calmette-Guerin (BCG) in high-risk non-muscle-invasive bladder cancer (HR NMIBC).
Authors: Wang Zongren , Zhan Wenhao , Huang Bin , Luo Cheng , Chen Lingwu , Chen Junxing
Published: January 2024

618

Background: Previous studies have proved IAC could reduce the recurrence and progression of HR NMIBC. The KEYNOTE-057 study has supported the benefits of PD-1 inhibitor in HR NMIBC patients (pts). Our study was established to evaluate the efficacy and safety of IAC combined with tislelizumab and BCG as a bladder-preserving treatment for HR NMIBC pts. Methods: This open-label, single arm phase II study enrolled BCG-naïve HR NMIBC pts with papillary tumors (high-grade Ta or T1 tumors). Firstly, the papillary tumors should be removed all visible lesions by transurethral resection of bladder tumor (TURBT). Secondly, angiographic catheter was placed into the internal iliac arteries with Seldinger’s percutaneous technique, cisplatin (60 mg/m2) and epirubicin (50 mg/m2) were administered arterially in day 1 (D1), every 3 weeks for 2-4 cycles. And pts received tislelizumab 200 mg IVGTT in D1, every 3 weeks for 2-4 cycles. Finally, pts received 18 instillations of BCG plus at least 8 cycles of tislelizumab (200 mg IVGTT, every 3 weeks). Specifically, pts were started on an induction course of BCG with 6 instillations every week, followed by maintenance with 3 instillations every 2 weeks and 9 instillations every 4 weeks. The primary end point was disease-free survival (DFS) rate at 12 months (defined as no reappearance of high grade or T1 tumors or clinical stage development after the therapy). Secondary end points were bladder-preservation rate, OS and safety. Our study estimated a DFS rate at 12 months was no less than 55% and the study would enroll 27 pts. Results: By Sep. 2023, 13 eligible pts were enrolled. Ten pts were analyzed (male 80.0%; median age 58 years (39-77); pure TCC 80.0%; median tumor size 2.5 cm (0.6-5.4); multiple papillary tumours=60.0%; high-grade Ta=40.0%, T1=60.0%). Median follow-up was 16.4 months (10.8-33.9), the mean number of IAC cycles was 2.4, mean number of tislelizumab cycles was 15.8, and the median BCG instillations was 16 (11-18). The DFS rate at 12 month was 90.0% (95%CI, 71.5%-98.6%). One pt showed reappearance of high-grade Ta and received TURBT. The bladder-preservation rate at 12 months was 100% (95%CI, 100%-100%). The OS rate at 12 months was 100% (95%CI, 100%-100%). 3 pts experienced treatment related adverse events, including nausea (n=1, G2), myalgia (n=1, G2), fatigue (n=1, G2), neutropenia (n=1, G2) and fever (n=1, G3). Conclusions: Our preliminary results supported the use of IAC combined with tislelizumab and BCG as a promising bladder-preserving strategy for HR NMIBC pts. Clinical trial information: ChiCTR2200067146 .
PEMBROBLAD: Real world effectiveness and safety of immune checkpoint inhibitors in patients with advanced urothelial carcinoma with histological variants.
Authors: Amrane Karim , Campedel Luca , Bennamoun Mostefa , Gabriel Pierre-Etienne , Brouchet Nicolas , Pouessel Damien , Roulleaux Dugage Matthieu , Thibault Constance , Cancel Mathilde , Gout Mathilde , Flechon Aude , Huillard Olivier , Abbar Baptiste , Borchiellini Delphine , Doublet Louis , Augusto-Pelegrin Laetitia , Elouen Boughalem , Moinard-Butot Fabien , Dumont Clement , Barthelemy Philippe
Published: January 2024

624

Background: A non-negligible portion of bladder cancers have non-pure UC histology; these tumors are often underdiagnosed and represent an unmet treatment need. Efficacy of immune checkpoint inhibitors (ICI) in non-pure UC remains unknown. We report preliminary data form the PEMBROBLAD study assessing ICI in pretreated mixed variants (UC-V) or pure non-UC (NUC) in real life condition. Methods: PEMBROBLAD is a retrospective multicenter study conducted in 24 French GETUG centers. Eligible patients had advanced UC with UC-V or NUC. All patients received ICI as a second line treatment. We excluded patients with ICI maintenance therapy. The primary endpoint was overall survival (OS); secondary endpoints included overall response rate (ORR), progression free survival (PFS), time to treatment failure (TTF) and safety. Results: A total of 139 patients (pts) were analyzed. Median age was 70 years (range 44-88), 70.8 % were male with ECOG PS 0/1, 2 and 3 in 57.7%, 26.6% and 10.1% of cases respectively. The most common variants of UC-V (n=96, 69.0%) were squamous cell differentiation (n=25, 26.0%), sarcomatoid (n=12, 12.5%), micropapillary (n=9, 9.3%), neuroendocrine (n=8, 8.3%), nested (n=7, 7.3%) and adenocarcinoma (n=5, 5.2%); squamous cell carcinoma (n=23, 53.4%) represented the majority of NUC (n=43, 31.0%). At data cutoff (August 15, 2023), median follow-up was 35.1 months (mo) (range 3.7-86.9). The most administered ICI was pembrolizumab in 85.6% of cases followed by durvalumab in 12.2% of cases. Median OS was 6.1 mo for all pts, 6.1 and 5.9 for UC-V and NUC respectively. In pts with UC-V and NUC, ORR was 31.2 % (n=30) and 18.6% (n=8) and DCR was 41.6% (n=40) and 23.2% (n=10) respectively. In all 139 pts, median TTF was 2.2 mo (95% CI, 0.1-50.0 mo). Serious TRAE occurred in 13 pts (9.3%). Discontinuation due to TRAEs occurred in 5.0% of pts. Conclusions: Our results suggest some efficacy of ICI in pretreated advanced UC-V and NUC. No new safety concerns were identified. Updated results with subgroup analysis will be reported at the meeting. [Table: see text]
Randomized phase III clinical trial of neoadjuvant intravesical mitomycin C (MMC) treatment in patients with primary treatment-naïve vesical neoplasms: Interim analysis.
Authors: Saita Alberto , Hurle Rodolfo , Arena Paola , Pozzi Chiara , Cieri Miriam , Colombo Piergiuseppe , Lazzeri Massimo , Lughezzani Giovanni , Buffi Nicolò Maria , Fasulo Vittorio , Paciotti Marco , Mancon Stefano , Lizier Michela , Morenghi Emanuela , Rescigno Maria , Casale Paolo
Published: January 2024

626

Background: The aim of the current study is to evaluate the safety, tolerability, and efficacy of neoadjuvant MMC in patients (pts) with non-muscle invasive bladder cancer (NMIBC). Methods: This is a prospective phase III randomized clinical trial in pts with primary clinical diagnosis of urinary bladder cancer or secondary recurrent untreated bladder cancer since May 2022 to September 2023 (EudraCT 2021-003751-42_studio ICH-013-). Pts are randomized 1:1 to neoadjuvant MMC arm (neoA) or standard arm (StA). In the 2 weeks before scheduled TUR (day 0) neoA pts receive intravesical instillations of MMC (40 mg/40 ml saline) at day -14 and -7 and cystoscopy with a cold cup biopsy at -14. After TUR, clinical choices both in the two groups, depend on histological evaluation of the tumour and EAU guidelines. Midstream and catheter urines are collected before instillations, at day 0 and after 3 months to respectively measure the level of specific biomarker (i.e., HMGB1) and to identify the microbiota. The expression of a mitomarker is evaluated on tissue samples. The primary endpoint is to assess safety, tolerability, and efficacy of neoadjuvant MMC in reducing the recurrence rate of BC calculated as the proportion of pts who achieve a complete response (no evidence of BC after 3, 6, 12 and 24 mo). The secondary endpoint will be the analysis of the rate of grade and stage progression to MIBC in case of recurrence and the correlation with biomarkers. Results: The interim analysis (median follow-up 6 months) included 54 pts: 26 in the StA and 28 in the neoA. Respectively in StA and neoA mean age at TUR was 66.5 (±9.9) and 65.8 (±9.9), males were 23 (88.46%) and 24 (85.71%). No statistically significant difference was observed between groups. 5 neoA pts [17.86% (95%CI 6.06-36.89)] after instillations reported 4 different adverse reactions, grade 1 of Clavien Dindo classification. NeoA pts showed higher level of HMGB1 at day 0 and after 3 months, suggesting an increased induction of immunogenic cell death (ICD). Shotgun metagenomics on microbial DNA from catheter urine is still ongoing. In field recurrence has been observed in 1 (3.85%) StA and 2 (7.14%) neoA pts. Conclusions: Preliminary data show neoadjuvant MMC to be safe and well tolerated and seem to correlate with increase of HMGB1. The short follow-up and the small sample size do not allow conclusion on the efficacy. Clinical trial information: EUCTR2021-003751-42 .
Clinical and patient factors associated with treatment intensification for metastatic castration-sensitive prostate cancer.
Authors: Appukkuttan Sreevalsa , Williams Troy , Jhaveri Jay , Campbell David , Kong Sheldon , Kalayeh Bashir , Ramsey Scott David
Published: January 2024

63

Background: Intensified therapies convey a survival advantage over androgen deprivation therapy (ADT) alone in metastatic hormone sensitive prostate cancer (mHSPC). We sought to identify area- and patient-level factors that are associated with intensification of therapy among mHSPC patients treated in US health systems. Methods: Electronic health records from OPTUM were used to identify patients aged ≥18 with mHSPC who received ADT between 2020 and 2022. Treatment intensification was defined as receiving one of the following within 90 days of initiation of ADT: apalutamide, enzalutamide, abiraterone +/- prednisone +/- docetaxel, darolutamide +/- docetaxel, docetaxel +/- other systemic therapy, and external beam radiation therapy (EBRT). Multivariable logistic regression was used to determine factors associated with intensification. We used Chi-squared tests to select the model with the best statistical fit. Results: We identified 1,123 patients with mHSPC who received ≥1 ADT in the post-index period with mean age of 71.2 (9.5), 73% Caucasian, 18% African American, and 2% Asian. Overall, 640 (57%) patients received treatment intensification within 90 days of ADT initiation. The proportion of patients receiving intensification increased from 53% to 63% between 2020 and 2022. The most common intensification treatments were abiraterone acetate (46%) and enzalutamide (38%). The median time to first treatment after metastasis was 15 days for receiving intensified therapy and 34 days for non-intensified therapy. In multivariable logistic regression, younger age, presence of bone/bone marrow metastasis at baseline, region (Northeast and West), and lower modified Charlson Comorbidity Index (CCI) score (excluding cancer) were significantly associated with receiving intensified therapy (Table). PSA was not included in models due to substantial missingness (40%). Conclusions: Just over half of eligible patients received treatment intensification following ADT. There are also significant disparities in treatment by age, region, and site of metastases. Future studies examining physician and patient preferences for intensification, as well as possible misperceptions and biases, would provide evidence to address undertreatment in this setting. [Table: see text]
GCISAVE: A non-comparative randomized phase II study of combination of gemcitabine cisplatin (GCis) +/- avelumab (A) in 1st line treatment for locally advanced or metastatic urothelial bladder carcinoma (MUBC)—GETUG AFU V07.
Authors: Gross-Goupil Marine , Frison Eric , Roubaud Guilhem , Flechon Aude , Calcagno Fabien , Rolland Frederic , Joly Florence , Raymond Anne-Aurelie , Chotard Guillaume , Barthelemy Philippe , Pouessel Damien , Thibault Constance , Culine Stephane , Linassier Claude , Ravaud Alain
Published: January 2024

637

Background: GCis is the standard 1st line of MUBC. Immune Checkpoint Inhibitor (ICI) is indicated as maintenance with avelumab (A), in patients (pts) with objective response or stable disease after chemotherapy, or as 2ndline with Pembrolizumab, in case of disease progression. Survival improvement of combining ICI to GCis still remains under investigation. GCISAVE evaluates the efficacy and safety of combining avelumab (A) with GCis in 1st line treatment. Methods: GCISAVE is a prospective multicenter randomized (2:1) non-comparative open-label phase II study, assessing the efficacy and safety of 6 cycles of GCis +/- A on a two-stage Bryant-Day design. Pts fit for cisplatin received GCis (G 1000 mg/m2, D1,D8; Cis 70 mg/m2, D1) +/- A (10 mg/kg, D1), every 3 weeks. Stratification was on centre, Karnofsky and visceral vs. non-visceral metastases. Two co-primary endpoints were the objective response rate (ORR) at week 18 (target≥ 60%) and the incidence of grade ≥3 treatment related adverse events (TRAE) (target<30%). Secondary objectives included: duration of response, 18 month PFS and OS;describing ORR according to the expression of PD-L1, immune infiltrate population and proteomics. Results: Between 11/2017 and 11/2020, 65 pts have been included, 42 (GCis+A) and 23 (GCis). Study was stopped prematurely due to the approval of A as maintenance treatment. Clinical characteristics were well balanced. 20 pts (47.6 %) in GCis + A arm and 7 pts (31.8 %) in GCis arm achieved 6 cycles with cisplatin : male (83.3 and 81.8%), median age (68 (62-71) and 67(56-72) yo), M1 stage for 76.2 and 77.3% respectively. 18 pts (42.9 %) in GCis + A and 13 pts (59.1 %) in GCis crossed to carboplatin. At week 18, ORR was 79.5% in the (GCis+A), including 15% Complete Response (RC) (39 pts evaluable), and 59.1% (GCis) arm (22 pts evaluable) respectively. TRAE were reported in 11 pts (26.2 %) in GCis+A arm. An oncoprot signature was obtained for CR and Partial Response compared to Progressive Disease (PD). Conclusions: GCis+A achieved the predefined target values with ORR ≥60% and ≤30% of SAE in 1st line treatment of MUBC. An oncoprot panel seemed to be correlated to PR, CR vs. PD. Clinical trial information: NCT03324282 .
Impact of intraoperative tranexamic acid use on overall survival and cancer specific survival in patients undergoing radical cystectomy.
Authors: Ahmed Mohamed E. , Andrews Jack R. , Mahmoud Ahmed M. , Thapa Prabin , Khanna Abhinav , Shah Paras , Sharma Vidit , Thompson R. Houston , Tollefson Matthew K. , Frank Igor , Karnes R. Jeffrey
Published: January 2024

642

Background: Perioperative blood transfusion has been reported in up to 60% of patients undergoing RC. Unfortunately, perioperative blood transfusion in patient undergoing RC has been associated with poor oncological outcomes. Tranexamic acid (TXA) use has been proposed to decrease the need for perioperative blood transfusion. Here we seek to investigate the impact of intraoperative TXA on survival outcomes in patients undergoing radical cystectomy (RC) for bladder cancer. Methods: We queried the prospectively maintained Mayo Clinic Radical Cystectomy registry and identified all RC performed for bladder cancer between 1990-2021. Primary outcomes were patient’s overall survival and cancer specific survival among patients who received TXA versus patients who did not receive TXA. Results: Among 2929 patients who underwent RC in our institution between 1990-2021, 468 received TXA (IV) intraoperatively (Group A) and were propensity score matched 1:1 for age, neoadjuvant chemotherapy, adjuvant chemotherapy, pT stage, pN stage, and preoperative hemoglobin with a group who did not receive TXA (Group B, n= 468). At 8 years followup, 61% of patients who received TXA were alive versus 46% of patients who did not receive TXA. In univariable and multivariable analyses of factors associated with CSS (Table1), node positive disease, pT2-T4, peri-operative blood transfusion were associated with poor survival outcomes. While use of TXA was associated with improved CSS outcomes. Conclusions: In our study, TXA use in patients undergoing radical cystectomy was associated with decreased risk or peri-operative transfusion, improved patient’s overall survival, and cancer specific survival. We can’t explain the biological rational for improved survival however these findings warrant further prospective investigation. [Table: see text]
Impact of squamous histology on outcomes with enfortumab vedotin in patients with advanced urothelial carcinoma: Analysis of the UNITE study.
Authors: Jindal Tanya , Alhalabi Omar , Nguyen Charles B , Bakaloudi Dimitra Rafailia , Nizam Amanda , Bilen Mehmet Asim , Basu Arnab , Zakharia Yousef , Milowsky Matthew I. , Brown Jason R , Kilari Deepak , Shah Sumit , Emamekhoo Hamid , Grivas Petros , Hoimes Christopher J. , Gupta Shilpa , Bellmunt Joaquim , Campbell Matthew T , Alva Ajjai Shivaram , Koshkin Vadim S
Published: January 2024

651

Background: Squamous histology (SH) is the most common variant of Urothelial Carcinoma (UC) and is associated with lower response rates to chemotherapy. The impact of SH on outcomes with enfortumab vedotin (EV) is less defined. We hypothesized that increased SH component would correlate with inferior outcomes with EV treatment. Methods: UNITE is a multi-institutional retrospective study in pts advanced UC (aUC) treated with targeted agents. In this analysis, we compared EV monotherapy outcomes in pts with pure UC (pUC) and pts with urothelial predominant histology (UCP) [<50% SH], SH-predominant [50-99% SH] and pure SH (pSH) [100% SH] respectively. We also compared pSH to UCP and SHP. Observed Response Rate (ORR) was compared in evaluable pts with scans after ≥1 cycle of EV using Chi-squared test. Progression-free survival (PFS) and overall survival (OS) from EV start were assessed and compared using the KM method and Cox proportional hazard test. Results: This analysis included 460 pts from 17 US sites treated with EV monotherapy. 366 pts had pUC and 94 pts had SH component (including pSH). In the overall cohort, median age was 70, 73% men, 88% Caucasian, 73% ECOG PS 0-1, 67% lower tract tumor, 30% liver mets, 38% bone mets, 65% had ≥ 2 prior therapy lines. There were no significant differences in baseline clinical characteristics between pts with pUC vs SH component except for higher incidence of liver mets in pts with pUC (32% vs 20%; p = 0.02). Among all 460 pts, median follow up was 20.7 mos from EV start, ORR was 51%, mPFS and mOS were 5.8 mos (95% CI: 5.3-6.4) and 12.7 mos (95% CI: 11.5-14.3). Among 94 pts with SH component, 70 were UCP, 17 SHP and 7 pSH. Inferior outcomes were noted in pts with pSH relative to pts with pUC and pts with UCP (Table). No differences in outcomes were seen across other cross-group comparisons. Conclusions: These hypothesis-generating findings suggest that SH component may impact outcomes with EV treatment in pts with aUC. A subset of pts with SH-predominant histology can have robust responses and outcomes with EV treatment, but larger studies and further biomarker data are needed to determine pts most likely to benefit. Patients with pSH are shown to have worse outcomes with EV, but further studies with a larger sample size are needed to validate our findings and define the role of EV for this rare and biologically distinct entity. [Table: see text]