BACKGROUND:The phase II trial CABRAMET evaluates the efficacy of the VEGFR tyrosine kinase inhibitor (TKI) cabozantinib in patients with non-locally pretreated brain metastases (BM) from renal cell carcinoma (RCC). Faced with historical challenges in treating BM in RCC, this study aimed to provide prospective data on systemic treatment outcomes. PATIENTS AND METHODS:This multicenter open-label trial included RCC patients with BM with less than three prior systemic treatments excluding cabozantinib. Eligible patients received 60mg/day oral cabozantinib with dose adjustments for toxicity. The primary endpoint was the 6-month progression-free rate in brain metastases (6m-BM-PFR). The main secondary endpoints included BM objective response rate (ORR) and response duration in BM, extra-cranial ORR, BM and overall progression-free survival (PFS), overall survival (OS), and safety. RESULTS:The study enrolled 26 patients, with a median follow-up of 38.8 months (range 28.3-52.7 months). The 6m-BM-PFR was 56% (unilateral 95%CI 37.9-) by central review. BM partial responses were achieved in 16/26 patients (BM ORR of 61.5%) by investigator assessment. The median BM response duration was not reached and 58.3% (95%CI 29.3-78.9%) of the patients were event-free at 24 months. The median BM-PFS was 10.7 (95%CI 5.4-NR) months, and the median overall PFS was 8.1 (95%CI 4-11.9) months. The median OS was 15.0 (95%CI 9.3-35.0) months. Cabozantinib exhibited significant efficacy as first-line treatment with BM ORR of 86%, 67% in patients with prior immunotherapy, 40% in patients previously treated with TKI. CONCLUSION:The CABRAMET trial is the first to prospectively assess cabozantinib in the challenging population of non-locally pretreated brain metastases from RCC, highlighting its prolonged efficacy and tolerability in selected patients with BM. CLINICAL TRIAL REGISTRATION:NCT03967522.

BackgroundIn contemporary health care, patient-centered care has emerged as a pivotal paradigm shift that redefines the traditional physician-centric model. Particularly in the context of cancer care, marked by its intricate nature and emotional impact, there is a pressing requirement to rethink how health care is delivered. In this context, comprehensive cancer care networks (CCCNs) provide a new means of structuring and delivering quality cancer care, recognizing each patient’s unique preferences and needs. ObjectiveThis study aimed to establish a consistent definition and framework for patient centeredness in CCCNs, facilitating the integration of a patient-centered approach to enhance care quality. MethodsWe conducted an umbrella review focusing on generic and oncology-specific dimensions of patient centeredness to establish the definition and framework. The data were analyzed and synthesized using an inductive category development approach, which guided the derivation of dimensions for the framework. The review was complemented by a survey of 23 key stakeholders within CCCNs and a focus group with patient representatives. This process involved iterative group discussions to achieve consensus on the framework and definition. ResultsThe study presents a robust definition and framework of patient centeredness tailored to CCCNs, validated by an initial agreement rate of 96% among survey respondents. Patient centeredness in a CCCN is defined as a philosophy of care prioritizing the physical, emotional, and social needs and personal values of patients with cancer at every step of the patient pathway. In patient-centered CCCNs, patients are empowered and engaged in becoming active partners in health care in relation to their individual preferences and capabilities, with the goal of providing personalized, high-quality, holistic care with the best possible outcomes. The framework comprises 8 primary dimensions: empowering patients, engaging and involving patients, treating the patient as a unique person, enhancing the therapeutic relationship, enhancing a patient-centered culture, providing holistic care, recognizing and supporting the health care professional as a person, and coordinating care. Each dimension is supported by specific subdimensions and actionable patient-centered activities that facilitate practical implementation. ConclusionsThe results provide a comprehensive perspective on the complex elements that compose patient-centered care within CCCNs in Europe. This contributes to a better understanding and application of patient centeredness in cancer care and possibly other contexts. The results presented in this paper promise to support cancer care networks and other health care contexts in creating a patient-centered environment where patients feel genuinely heard, valued, and actively engaged in their care decisions.

533 Background: Despite dramatic progress in metastatic RCC treatments, pts with BM remain with poor outcome and were mostly excluded from clinical trials. Local treatments on BM are standard today. Methods: Adult pts with histologically proven RCC and BM ≥ 5 mm (or > 8 mm if solitary) including at least one non-locally pretreated, < 3 prior systemic treatments excluding cabozantinib, ECOG PS 0 or 1 and steroids < 40 mg/day were included. Primary endpoint was BM progression free survival rate at 6 months (6m-BM-PFS) according to modified RANO-BM criteria by central review. Secondary endpoints were BM response and response duration, extracranial response, PFS, overall survival and safety. 25 evaluable pts were required to evaluate the main endpoint. Results: 26 pts were included, 25 were evaluable for the primary endpoint and median follow up time was 39.8 months [5.9-49.7]. The 6m-BM-PFS was 56.0% [unilateral 95%CI 37.9-] (14/25 pts). BM response was partial response (PR) for 61.5% (16/26) pts and median duration of response was not reached, 66.7% pts being event-free 24 months after BM response. Extracranial response was PR for 38.5% (10/26). Median PFS was 8.1 months [95%CI 4-11.9], and median BM PFS 8.4 months [95%CI 5.4-NR]. Median overall survival was 15.8 months [95%CI 9.7-35.0]. No new safety signals were observed. Conclusions: This is the first prospective trial assessing cabozantinib in RCC pts with non-locally pretreated BM. These results confirm the efficacy of cabozantinib on BM previously reported in retrospective series. Clinical trial information: NCT03967522 . Pts characteristics. Pts number N = 26 Median age (years) [range] 67 [44-86] Gender: F / M, n 5 / 21 ECOG PS: 0 / 1,n 10 / 16 RCC: non-clear cell / clear cell, n 2 / 24 Prior nephrectomy : n 16 Number of BM: 1 / 2 / >3, n 9 / 7 / 10 Prior BM treatments: Overall/ Surgery/ Radiation, n 10 / 3 / 10 Prior systemic treatment: 0 / 1 / >2, n 7 / 15 / 4 IMDC: Favorable / Intermediate / Poor, n 7 / 10 / 9

Objective:To develop an evidence-based reference model defining the exact boundaries of the missions and activities of the hospital-based cancer care coordination nurses, to clarify their roles and standardise practices for impact evaluation. Methods and analysis:Design: A multiphase, mixed-methods modelling study was conducted. First, we collected qualitative and quantitative data on cancer coordination nursing practices through a multicentre cross-sectional study. Mixed data were mapped to a previously developed reference framework to derive the reference model. Setting: 10 French hospitals, varying in size and status, over 20 months (2018-2019). Participants: Thirty-six hospital-based cancer coordination nurses, 162 patients, 142 caregivers and 352 healthcare professionals from both hospital and primary care settings. Main outcome measures: Qualitative data on roles, activities and experiences were collected through observations, interviews and focus groups. Quantitative data on role perceptions and organisational context were gathered using standardised questionnaires assessing support, commitment, role conflict, patient quality of life, precariousness and caregiver burden. Results:We identified core missions such as active listening, clinical needs assessment and internal coordination, but also differences leading to a nurse typology into three groups: 'complex pathway coordinators', 'treatment specialists' and 'polyvalent nurses'. Only 'complex pathway coordinators', fully aligned with the reference framework, performed complete care coordination and correspond to the reference model. Conclusion:The modelling provides a foundation for standardising cancer care coordination practices, improving training and establishing a standard intervention for evaluating cancer care navigation which the authors are still calling for. Trial registration number:NCT03350776.

In the past decade, the therapeutic arsenal for metastatic bladder cancer has expanded considerably, with the development of immune checkpoint inhibitors (ICIs), antibody–drug conjugates such as enfortumab vedotin, and anti-fibroblast growth factor receptor agents. Clinical trials evaluating ICIs as neoadjuvants, adjuvants, or first- or second-line treatments have produced conflicting results. However, first-line therapeutic strategies have been redefined by the recent publication of results from two clinical trials: CheckMate-901, which demonstrated the superiority of combined treatment with nivolumab and chemotherapy in extending overall survival, and EV-302, which demonstrated that combined treatment with pembrolizumab and enfortumab vedotin reduced the risk of death by 53%. In this review, we discuss the role of ICIs, alone or in combination, in bladder cancer management in the metastatic and adjuvant settings in 2024, considering the latest published trials. The potential role of ICIs as neoadjuvants is also discussed.

The following ESMO Clinical Practice Guideline (CPG) has been recently updated with new treatment recommendations and an updated algorithm for managing treatment-naive advanced or metastatic urothelial carcinoma (stage IV): Bladder cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.1

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 .

You have accessJournal of UrologyAdrenal/Renal Oncology I (V04)1 May 2024V04-12 LEVEL 2 VENA CAVA THROMBECTOMY AND ROBOT ASSISTED RADICAL NEPHRECTOMY FOLLOWING IMMUNOTHERAPY Gaëlle Margue, Fabien Moinard-Butot, Jonathan Thouvenin, Baptiste Sionneau, Abderrahmane Khaddad, Marine Gross-Goupil, Alain Ravaud, Franck Bladou, Grégoire Robert, Philippe Barthelemy, Strasbourg France, and Jean-Christophe Bernhard Gaëlle MargueGaëlle Margue , Fabien Moinard-ButotFabien Moinard-Butot , Jonathan ThouveninJonathan Thouvenin , Baptiste SionneauBaptiste Sionneau , Abderrahmane KhaddadAbderrahmane Khaddad , Marine Gross-GoupilMarine Gross-Goupil , Alain RavaudAlain Ravaud , Franck BladouFranck Bladou , Grégoire RobertGrégoire Robert , Philippe BarthelemyPhilippe Barthelemy , Strasbourg FranceStrasbourg France , and Jean-Christophe BernhardJean-Christophe Bernhard View All Author Informationhttps://doi.org/10.1097/01.JU.0001009444.59519.d3.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The aim was to present a robot assisted level 2 vena cava thrombectomy and cytoreductive nephrectomy with retroperitoneal lymph node dissection in a patient previously treated with immunotherapy. METHODS: The surgery was performed using the Da-Vinci Xi surgical robot (Intuitive surgical). We used 3 operative arms, a 30° optic and 2 trocars (5 and 12 mm) for the assistant. Thrombus extension was assessed using an intraoperative ultrasound (Hitachi). RESULTS: Our patient was a 69-year-old man diagnosed with poor prognosis clear cell renal cell carcinoma (ccRCC) with synchronous lymph node invasion and pulmonary metastases in a context of anemia. He was initially treated with combined immunotherapy (NIVOLUMAB+IPILIMUMAB) followed by NIVOLUMAB every month for seven months. A complete response to immunotherapy was observed on metastatic sites and a partial response on the thrombus, mainly a diameter reduction without level's lowering. Surgical management with robot assisted radical nephrectomy, vena cava thrombectomy and retroperitoneal lymph node dissection was decided. After colonic detachment, anterior and lateral sides of the vena cava were dissected, and ultrasound was performed to visualize thrombus extension. Dissection was continued at the posterior face of the vena cava and lateral side of the aorta. Right renal artery was clipped and sectioned. Vascular clamps were placed on the left renal vein, subrenal vena cava and subhepatic vena cava to allow single block cavotomy and thrombectomy. Abundant irrigation of the vena cava was performed before complete closure. Finally, radical nephrectomy and retroperitoneal lymph node dissection were completed after unclamping. The length of surgery was three hours and a half with 15 minutes of vena cava clamping and an estimated blood loss of 200 mL. The pathological report confirmed an ISUP 3, ccRCC of 9 cm with carcinomatous thrombus and significant fibrous and necrotic remodeling. A french retrospective multicentric study included 44 metastatic patients with venous thrombus and treated with immunotherapy. It showed a response rate of about 36% but mostly on diameter without change in thrombus level which is consistant with our case. CONCLUSIONS: Surgical difficulties following immunotherapy are debated. In this case, the surgery was feasible with no more difficulties than without immunotherapy. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e199 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Gaëlle Margue More articles by this author Fabien Moinard-Butot More articles by this author Jonathan Thouvenin More articles by this author Baptiste Sionneau More articles by this author Abderrahmane Khaddad More articles by this author Marine Gross-Goupil More articles by this author Alain Ravaud More articles by this author Franck Bladou More articles by this author Grégoire Robert More articles by this author Philippe Barthelemy More articles by this author Strasbourg France More articles by this author Jean-Christophe Bernhard More articles by this author Expand All Advertisement PDF downloadLoading ...

BACKGROUND:This study evaluated the cost-effectiveness of avelumab first-line (1L) maintenance therapy plus best supportive care (BSC) versus BSC alone for adults with locally advanced or metastatic urothelial carcinoma (la/mUC) that had not progressed following platinum-based chemotherapy in France.METHODS:A three-state partitioned survival model was developed to assess the lifetime costs and effects of avelumab plus BSC versus BSC alone. Data from the phase 3 JAVELIN Bladder 100 trial (NCT02603432) were used to inform estimates of clinical and utility values considering a 10-year time horizon and a weekly cycle length. Cost data were estimated from a collective perspective and included treatment acquisition, administration, follow-up, adverse event-related hospitalization, transport, post-progression, and end-of-life costs. Health outcomes were measured in quality-adjusted life-years (QALYs) and life-years gained. Costs and clinical outcomes were discounted at 2.5% per annum. Incremental cost-effectiveness ratios (ICERs) were used to compare cost-effectiveness and willingness to pay in France. Uncertainty was assessed using a range of sensitivity analyses.RESULTS:Avelumab plus BSC was associated with a gain of 2.49 QALYs and total discounted costs of €136,917; BSC alone was associated with 1.82 QALYs and €39,751. Although avelumab plus BSC was associated with increased acquisition costs compared with BSC alone, offsets of -€20,424 and -€351 were observed for post-progression and end-of-life costs, respectively. The base case analysis ICER was €145,626/QALY. Sensitivity analyses were consistent with the reference case and showed that efficacy parameters (overall survival, time to treatment discontinuation), post-progression time on immunotherapy, and post-progression costs had the largest impact on the ICER.CONCLUSIONS:This analysis demonstrated that avelumab plus BSC is associated with a favorable cost-effectiveness profile for patients with la/mUC who are eligible for 1L maintenance therapy in France.

TPS487 Background: Treatment of mRCC consists of combination of either Immune Checkpoint Inhibitor (ICI)-Tyrosine Kinase Inhibitor (TKI) for all IMDC prognosis group, or ICI-ICI for intermediate and unfavorable IMDC groups. Treatments are maintained until disease progression or toxicity for a total duration of 2 years for ICI, in routine. Acceptability and feasibility of treatment pause of the TKI, with no detrimental effect on efficacy were reported in the prospective STAR trial. The good-risk population is characterized by prolonged survival, close to that reported in the intermediate risk population group with a single adverse prognostic factor. Therefore, a pause of ICI-TKI could improve quality of life, safety, and total cost of care without detrimental impact on oncologic outcomes. Methods: This non-inferiority, randomized, open-label, multicenter, parallel-group trial (NCT05219318) aims to compare treatment pause versus treatment continuation in good or intermediate risk mRCC patients with only one prognostic factor and a confirmed objective response (complete or partial) at 12 months of treatment with ICI-TKI. 372 patients (186 in France) will be recruited in tertiary hospitals and randomized in a 1:1 ratio with stratification by center, prognostic group (good/intermediate) and response (complete/partial). The primary objective is to test the non-inferiority of treatment pause versus continuation, with the estimation of the difference in 12-month progression rate after randomization, and its one-sided 97.5% confidence interval. The non-inferiority margin is set at 15%. An interim safety data monitoring at 6 months after randomization of the first third of participants (i.e. 60 per arm) will check progression rate after treatment pause. A formal interim futility analysis will be performed when 50% of the study sample reaches the primary outcome time point, using a Bayesian predictive power stopping rule and a futility threshold set at 20%. Secondary objectives are overall safety and tolerability, health-related quality of life, anxiety and depression, quality-adjusted survival, 2-year overall and progression-free survival. Others objectives include progression patterns (site, known lesions, or/and new lesions), subsequent treatment (type, efficacy), in the experimental arm. In France, healthcare resource utilization and costs at 12 months will be compared. The first participant was randomized in January 2023. 27 centers in France were selected and are gradually/progressively opening. The opening of European centers is being planned. Health Ministry and National Cancer Institute Funds. Clinical trial information: NCT05219318 .

ORR in patients with sRCC and I/P-risk disease, per IRRC, by central or local pathology review.

PDF file - 25KB, Supplemental Table 2 contains a summary of the newly occurring qualitative ECG abnormalities.

Kaplan-Meier analysis of progression-free survival (PFS) and overall survival (OS) according to relative changes in biomarkers during cycle 1 (A-B) and cycle 2 (C). HR, hazard ratio; CI, confidence interval.

471 Background: In the phase 3 JAVELIN Bladder 100 trial, avelumab 1L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) vs BSC alone in pts with aUC that had not progressed with 1L platinum-based chemotherapy (CTx). The JAVELIN Bladder regimen is now standard of care with level 1 evidence in international treatment guidelines. The AVENANCE study (NCT04822350), is investigating the efficacy and safety of avelumab 1L maintenance in a real-world population of pts with aUC in France. Data from the full analysis set are reported for the first time. Methods: In this ongoing, noninterventional, ambispective study, eligible pts have locally advanced or metastatic UC that has not progressed with 1L platinum-based CTx and previous, ongoing, or planned avelumab 1L maintenance treatment. The primary endpoint is OS from start of avelumab; secondary endpoints include progression-free survival (PFS), duration of treatment (DOT), and safety. Results: 591 pts received avelumab. At data cutoff (July 31, 2022), median follow-up was 12.0 mo (95% CI, 10.9-12.9). Median age was 73.1 y (IQR, 67.0-78.1). At start of 1L CTx (excluding pts with missing data), disease stage was metastatic in 524 pts (90.5%; visceral metastases in 426 [81.5%]) and locally advanced in 54 (9.3%). ECOG PS was 0-1 in 407 pts (85.3%) and 2-3 in 69 (14.5%). Tumor histology was pure UC in 528 pts (91.8%) and UC with variant or pure variant in 47 (8.2%). 1L CTx was gemcitabine + carboplatin (GemCarbo), gemcitabine + cisplatin (GemCis), dose-dense methotrexate + vinblastine + adriamycin + cisplatin (DD-MVAC), and other in 353 (61.0%), 170 (29.4%), 28 (4.8%), and 28 (4.8%) pts, respectively. Median number of cycles was 5 (range, 1-10). Median DOT with avelumab was 5.8 mo (95% CI, 5.2-7.0); 241 pts (40.8%) remained on treatment at data cutoff. The most common reasons for treatment discontinuation were disease progression (74.1% [n=258]), death (11.5% [n=40]), and adverse events ([AEs] 10.3% [n=36]). Median OS from start of avelumab was 18.4 mo (95% CI, 15.4-not estimable [NE]), the 12-month OS rate was 64.8% (95% CI, 60.0%-69.1%), and median PFS was 5.7 mo (95% CI, 5.3-7.0). In pts who had received GemCarbo, GemCis, or DD-MVAC, median OS (95% CI) was 16.2 mo (13.4-NE), not reached (NR; 18.1-NE), and NR (15.2-NE), respectively. Subgroups analyses will be presented. 218 pts received subsequent 2L, including CTx, antibody-drug conjugates, immunotherapy, and other in 186 (85.3%), 22 (10.1%), 6 (2.8%), and 4 (1.8%) pts, respectively. Any-grade treatment-related AEs (TRAEs) occurred in 217 pts (36.7%), including serious TRAEs in 29 (4.9%). Conclusions: Real-world data for avelumab 1L maintenance in pts with aUC from AVENANCE support the findings of JAVELIN Bladder 100 and confirm the clinical activity and acceptable safety profile of avelumab in a heterogeneous population. Clinical trial information: NCT04822350 .

Primary renal tumor response on sunitinib according to MSKCC risk group

Treatment-free interval, duration of therapy, duration of response, and subsequent systemic therapy in all patients with sRCC and I/P-risk disease and confirmed response (A, complete responders; B, partial responders).

<p>Supplementary Figure S2. Cells resistant to sunitinib overexpress VEGFC. VEGFC mRNA and protein are overexpressed in sunitinib-resistant RCC cells. Such induction is linked to increased transcription and mRNA stability.</p>

Comparison of OS stratified by genotype and treatment group

Objectifs L’objectif était de présenter une néphrectomie totale de cytoréduction robot assistée avec thrombectomie cave de niveau 2 et curage rétropéritonéal chez un patient précédemment traité par immunothérapie.