N is approved in 2L mUC after platinum-based chemotherapy. Studies suggest improved outcomes for dual checkpoint inhibition in particular with high doses of ipilimumab (N 1mg/kg + I 3mg/kg). We report final data of TITAN-TCC, NCT03219775, that used a tailored approach with N and N+I boosts for non-response. Pts with mUC started N induction (240mg Q2W x4). Non-responders of cohorts 1 (dose escalation) and 2 (high dose ipilimumab) received N+I boosts as reported in the table. Responders to N induction continued with N maintenance (240mg Q2W), but could receive N+I per the respective schedules for later progression. Repeated boost phases were possible. Primary endpoint was objective response rate (ORR) to N ± N+I per RECIST1.1. Secondary endpoints included ORR to N induction, progression-free survival (PFS), and overall survival (OS). TITAN-TCC was conducted from 08/2017 to 02/2023. In cohort 1, 42 pts were 1L and 44 2/3L. Cohort 2 recruited 2/3L pts only with 83 being enrolled. For follow-up times see the table. ORR to N induction was 29%, 23%, and 20% for cohort 1 – 1L, cohort 1 – 2/3L, and cohort 2, respectively. In total, 105 pts received any boost doses, 14 had repeated boost phases. Best overall response to N ± N+I was 48% (95% CI 32-64), 27% (95% CI 15-43), and 33% (95% CI 23-44), respectively. 1-, 2-, and 3- year OS rates were 55%, 37%, and 31% for cohort 1 – 1L, 42%, 31%, and 18% for cohort 1 – 2/3L, and 40%, 34%, and 34% for cohort 2. For median OS and PFS see the table.Table: 2372PParameterCohort 1 - 1L N=42Cohort 1 - 2/3 L N=44Cohort 2 (2/3 L) N=83Boost schedule2x N 3mg/kg +I 1mg/kg (Q3W); if no response: 2x N 1mg/kg +I 3mg/kg (Q3W)2x N 3mg/kg +I 1mg/kg (Q3W); if no response: 2x N 1mg/kg +I 3mg/kg (Q3W)2x N 1mg/kg +I 3mg/kg (Q3W); if no response: 2x N 1mg/kg +I 3mg/kg (Q3W)Median age, years (range)70 (45-84)68 (45-80)68 (37-84)Median follow-up, months (range)10.4 (0.6-51.8)7.5 (0.3-60.3)5.6 (0.3-42.6)ORR N induction, n (%)12 (29)10 (23)17 (20)ORR N ± N+I, n (%)20 (48)12 (27)27 (33)Median OS, months (95% CI)16.4 (7.3-28.5)8.3 (5.3-19.3)7.6 (5.0-14.9)Median PFS, months (95% CI)3.0 (1.8-6.8)1.9 (1.7-5.8)1.9 (1.8-3.2) Open table in a new tab Despite meaningful clinical activity of the TITAN-TCC approach in cohort 1 – 1L, starting treatment with N monotherapy appears inadequate given the aggressiveness of mUC. In 2/3L, N+I boosts with escalating dose of ipilimumab (cohort 1 – 2/3L) did not improve ORR vs. N monotherapy as reported in the literature. However, it did for boosts with high dose ipilimumab (cohort 2) with a considerable 3-year OS rate for 2/3L mUC.

In mRCC patients combinations of tyrosine kinase inhibitors (TKI) and checkpoint inhibitors (CPI) are standards of care. We previously reported on our switch-maintenance approach (CPI after TKI) in mRCC. Today, we report on exploratory analyses that investigated predictive value of the PD-L1 status. Pts. with measurable clear cell mRCC, ECOG 0-2, adequate organ function and partial remission or stable disease to TKI therapy were eligible. 49 patients were randomized to early study termination between 12/2016 and 08/2018. After 12 weeks, 1:1 randomization to TKI continuation (24 pts.) or nivolumab (NIVO; 25 pts.; 240 or 480 mg IV q2-4wk) was performed. PD-L1 expression was determined by immunohistochemistry using the SP163 antibody clone and defined as combined positivity score (CPS) with setting 1 as cut-point for positivity (n=41). Objective response rate (ORR) was assessed according to RECIST 1.1. KM and log-Rank analyses were used for survival analyses. Median age was 65 years (range 35 - 79), 82% were male and 4% had ECOG PS 2. With metastases predominantly in lung (47%), lymph nodes (27%) and liver (24%). 55% received sunitinib. ORR for NIVO vs. TKI differed when assessed from randomization (16 vs. 48%; P=0.03). Accordingly, progression free survival (PFS) from randomization was 3.0 vs. 11.9 mo. (HR = 2.57 [95% CI: 1.36 – 4.89]) in favor for TKI continuation. With a 2-year OS of 64% for NIVO vs. 66% for TKI (HR = 1.12 [95% CI: 0.43 – 2.89]; P=0.82). ORR in CPS<1 vs >1 RCC was 13.3% and 40.0% for NIVO and 37.5% and 75.0% in TKI cases. Tumors with a CPS<1 most frequently showed PD as the best response in both arms. However, a greater proportion of patients reported PD for NIVO (n=9, 60.0%) compared to TKI (n=1, 12.5%). Continuation of TKI is more efficacious than early switch to NIVO, despite PD-L1 positivity. The major limitation of our trial is the premature closure and its limited sample size. Authoring Group Name: IAG-N of the German Cancer Society Sponsor, funding source: AIO-Studien-gGmbH, financial support BMS

In mRCC patients (pts) combinations of tyrosine kinase inhibitors (TKI) and checkpoint inhibitors (CPI) are considered standards of care. Our study investigated whether a 1st line switch-maintenance approach (CPI after TKI) improved outcome in mRCC. 49 mRCC pts. with partial remission (PR) or stable disease (SD) after 12 weeks TKI induction therapy were 1:1 randomized to receive either TKI continuation (24 pts.) or nivolumab (NIVO; 25 pts.; 240 or 480 mg IV q2-4wk). Objective response rate (ORR) (according to RECIST 1.1), progression free survival (PFS) and adverse events (AE, according to CTCAE v4.03) were assessed from time of randomization. KM plots/log-Rank analyses were used for time to event analyses. PRO were assessed by the FACT Kidney Symptom Index (FKSI-15). Time to deterioration (TTD) was defined as time between randomization to PRO decrease ≥3 points. Data base was closed on December 2020. Median age was 65 years, 82% were male and 4% had ECOG 2. Main metastatic sites were lung (47%), lymph nodes (27%) and liver (24%). MSKCC risk was favorable in 31%, intermediate in 65% and poor in 4%. Response to TKI induction therapy was PR in 59% and SD in 41% of pts. ORR from randomization favored TKI continuation (16 vs. 48%; P=0.03). After a median follow-up of 26.3 mo (1.3-45.6), 40 PFS events and 17 deaths occurred. PFS was 3.0 vs. 11.9 mo. (HR = 2.57 [95% CI: 1.36 – 4.89]) in favor for TKI continuation. Median OS was not reached. 2-year OS was 64% for NIVO and 66% for TKI treatment (HR = 1.12 [95% CI: 0.43 – 2.89]; P=0.82). AEs for NIVO vs. TKI occurred in 96% vs. 100%, grade 3-5: 56% vs. 71% and serious AE (SAE): 48% and 50%, respectively. Median FKSI15 score at therapy initiation to end of therapy showed no significant difference, 46 and 47 for NIVO as well as for TKI with 42 and 43. Median TTD favoured NIVO (NR) vs. TKI (6.9 mo), but difference remained insignificant (P=0.16). Our data does not support the use of a switch-maintenance approach in mRCC. Although a lower degree of grade ≥3 AEs for NIVO was observed, a PRO benefit was not detected. A major limitation is the small sample size and the selection of TKI-sensitive pts.

Das Nierenzellkarzinom ist der dritthaufigste Tumor auf dem urologischen Fachgebiet. Die Therapie kleinerer Tumoren besteht zunehmend in organerhaltenden Ansatzen wie der partiellen Nephrektomie, fokalen Ablation mittels Kryoablation oder Radiofrequenzablation oder auch der aktiven Uberwachung. Diese Therapieformen erhohen die Anforderungen an eine Tumornachsorge. Wie sind die aktuellen Empfehlungen zur Nachsorge des Nierenzellkarzinoms aufgrund der neuen Therapiemoglichkeiten? In der vorliegenden Arbeit werden die verschiedenen tumorbiologischen Aspekte, die diagnostischen Moglichkeiten der Tumornachsorge sowie die Empfehlungen der verfugbaren Leitlinien (S3-Leitlinie, EAU-Leitlinie [European Association of Urology] und AUA-Leitlinie [American Urological Association]) dargestellt. Die Nachsorge des Nierenzellkarzinoms ist nicht sehr standardisiert, insbesondere weil die Datenlage begrenzt ist. Prinzipiell sollte die Nachsorge in den ersten 3 Jahren nach der erfolgten Therapie und bei Patienten mit einem erhohten Rezidivrisiko intensiver vorgenommen werden. Fur die Risikoeinteilung stehen mehrere Prognosemodell zur Verfugung, die ausschlieslich auf klinischen Parametern basieren. Bisherige Empfehlungen zur Nachsorge des Nierenzellkarzinoms basieren auf retrospektiven Analysen. Zukunftige Nachsorgestrategien sollten (noch zu bestimmende) Marker einschliesen und prospektiv gepruft werden.

Das Nierenzellkarzinom ist der dritthäufigste Tumor auf dem urologischen Fachgebiet. Die Therapie kleinerer Tumoren besteht zunehmend in organerhaltenden Ansätzen wie der partiellen Nephrektomie, fokalen Ablation mittels Kryoablation oder Radiofrequenzablation oder auch der aktiven Überwachung. Diese Therapieformen erhöhen die Anforderungen an eine Tumornachsorge. Wie sind die aktuellen Empfehlungen zur Nachsorge des Nierenzellkarzinoms aufgrund der neuen Therapiemöglichkeiten? In der vorliegenden Arbeit werden die verschiedenen tumorbiologischen Aspekte, die diagnostischen Möglichkeiten der Tumornachsorge sowie die Empfehlungen der verfügbaren Leitlinien (S3-Leitlinie, EAU-Leitlinie [European Association of Urology] und AUA-Leitlinie [American Urological Association]) dargestellt. Die Nachsorge des Nierenzellkarzinoms ist nicht sehr standardisiert, insbesondere weil die Datenlage begrenzt ist. Prinzipiell sollte die Nachsorge in den ersten 3 Jahren nach der erfolgten Therapie und bei Patienten mit einem erhöhten Rezidivrisiko intensiver vorgenommen werden. Für die Risikoeinteilung stehen mehrere Prognosemodell zur Verfügung, die ausschließlich auf klinischen Parametern basieren. Bisherige Empfehlungen zur Nachsorge des Nierenzellkarzinoms basieren auf retrospektiven Analysen. Zukünftige Nachsorgestrategien sollten (noch zu bestimmende) Marker einschließen und prospektiv geprüft werden.

Concepts for measuring and improving the quality of patient care in hospitals have become increasingly important in recent years.The peer review procedure which has been developed by the Helios Clinic Group and Initiative for Quality Medicine (IQM) is described.In peer review, medical records are reviewed by experienced external physicians. Inadequacies are identified, improvement protocols initiated, and concrete measures for improvement of patient care derived.The described procedure is able to identify patient risks and errors during the course of treatment with the subsequent goal of avoiding repetition. In a retrospective, observational quality management study, peer review led to a significant decrease in mortality rates for various diseases.Peer review represents the optimal procedure of medical quality management by systematic review and open discussion with colleagues.

4584 Background: The therapeutic landscape for metastatic renal cell carcinoma (mRCC) has evolved rapidly with the approval of targeted therapies like tyrosine kinase-, mTOR-, multikinase-, and immune checkpoint inhibitors. Real-world data are urgently needed to monitor the translation of these approaches into daily practice. Methods: PAZOREAL is a prospective, non-interventional study to evaluate efficacy, tolerability, safety, and quality-of-life (QoL) in mRCC patients (pts) treated with first-line PAZO, second-line nivolumab (NIVO) or EVE, or third-line EVE (± lenvatinib) after NIVO. The primary variable was time on drug (TD) in the respective Tx lines. Other endpoints were overall survival (OS), dosing, safety, and QoL. Results: Between Dec 2015 and Nov 2017, 421 pts were enrolled. Interim results for 385 pts treated with PAZO in first line are presented here, majority of pts presented with ECOG 0-1 (81.0%) and clear cell carcinoma (80.3%). Median TD was 6.5 months (95%CI, 5.5-8.3). Using commonly applied trial eligibility criteria i.e. Karnofsky PS ≥ 70%, normal hemoglobin and clear-cell histology, the median TD in trial-eligible pts (39.5% of 385 pts) was 8.0 months (95%CI, 6.2-11.2). Progressive disease (n = 104/212 pts) was the most common reason for end of PAZO Tx, followed by toxicity (n = 34) and unrelated adverse events (AEs) (n = 20). 75 pts subsequently received NIVO as second-line treatment. Median OS was not reached. Death was reported for 20.8% of pts. Survival follow-up is ongoing. PAZO Tx was well tolerated. Treatment-emergent AEs (TEAEs) were reported for 308 of 378 pts included in the safety analysis, PAZO-related TEAEs for 246 pts (65.1%), and PAZO-related grade 3/4 TEAEs for 75 pts (19.8%). Most commonly reported AEs were diarrhea, nausea, and fatigue. QoL evaluated by EQ-5D-5L remained stable during PAZO Tx. Conclusions: The PAZOREAL study demonstrated acceptable efficacy, safety and tolerability of PAZO in the real-world setting. For patients considered trial-eligible, TD was comparable with results from clinical trials. The sequence of PAZO followed by NIVO as second line Tx is commonly applied in Germany.

Die Etablierung qualitätssichernder Maßnahmen im Krankenhaus hat in den vergangenen Jahren zunehmende Bedeutung erlangt. Zielstellung ist es, die Behandlungsqualität durch Erkennung und konsekutive Vermeidung von Behandlungsfehlern zu verbessern.

Background: The treatment (tx) of metastatic renal cell carcinoma (mRCC) has markedly changed over the last decade with the introduction of targeted therapies including vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin (mTOR) inhibitors. Current tx recommendations include the VEGFR inhibitor pazopanib (PAZ) as first-line option and the mTOR inhibitor everolimus (EVE) after VEGF-targeted therapy. The approval of programmed cell death 1 (PD-1) checkpoint inhibitor nivolumab (NIVO) in 2016 provides an additional second-line option. Methods: PAZOREAL is a prospective, non-interventional study to evaluate the effectiveness, tolerability, safety and quality of life on the routine tx of 450 adult patients (pts) with histologically confirmed mRCC treated with first-line PAZ, second-line EVE or NIVO, or third-line EVE after NIVO. The main objective is time on drug (TD) in the respective tx lines and overall, other objectives include overall survival, dosing parameters, safety and quality of life. Results: Between December 2015 and March 2017, 305 pts have been enrolled; 302 in the first-line PAZ cohort and 3 in third-line EVE after NIVO. The latter cohort was opened for documentation after approval of NIVO. 266 first-line pts had a documented first intake of PAZ and were eligible for analysis; 201 (75.6%) had a clear-cell histology. Median TD on PAZ was 6.5 months. For 98 pts (36.8%) discontinuation of PAZ tx was reported. The main reasons were progressive disease (N = 36), followed by toxicity (N = 18) and (serious) adverse event (N = 13). Details on subsequent tx with NIVO or EVE were documented for 24 and 4 pts, respectively, while 8 pts started other therapies in second line. During PAZ tx, the most frequently reported treatment-emergent adverse events (TEAE) of grade 1/2 were diarrhea (N = 57), nausea (N = 36), and fatigue (N = 24), of grade 3/4 were hypertension (N = 11), diarrhea and anemia (each N = 4). Fatal TEAEs were reported in 28 pts with progression being the most common term. Conclusions: PAZ is an effective and safe first-line therapy for pts with mRCC in a real life setting. Second line therapy has rapidly shifted towards NIVO. Clinical trial identification: BfArM AWB No. 6687 Legal entity responsible for the study: Novartis Pharma GmbH Funding: Novartis Pharma GmbH Disclosure: J. Bedke: Reports consultancies, honoraria or study participation from Bayer, Bristol-Myers Squib, Novartis, Pfizer and Roche. M. Welslau: Reports grants from Novartis, during the conduct of the study. M. Schostak: Reports grants and other from Novartis, during the conduct of the study; and honorarium from Novartis for scientific talks. C. Hering-Schubert: Reports grants from Roche, Novartis, Amgen, Bristol-Myers Squib Boehringer and Cellgene, outside the submitted work T. Wolf: Nothing to disclose. J. Schleicher: Reports grants and personal fees from Bristol-Myers Squib, Novartis; grants from Essai, Celegene; personal fees from Jansen, Pfizer, outside the submitted work. V. Grünwald: Advisory role at Pfizer, Novartis, Bristol-Myer Squibb, Ipsen, Eisai, Roche and has received honoraria from Pfizer, Novartis, Bristol-Myer Squibb, Ipsen, Eisai and Roche. Research support is given from Pfizer, Novartis, Bristol-Myers Squib and MSD Merck. R. Ehness: Employee of Novartis Pharma GmbH and holds stocks or stock options of Novartis and of GSK. D. Klein, T. Medinger: Employed at iOMEDICO AG. P.J. Goebell: Received honoraria for participation in expert rounds and honoraria/support as a speaker from Astellas, AstraZeneca, Bayer, Bristol-Myers Squib, Eisai, Ipsen, Janssen, Novartis, Pfizer, Sanofi. All other authors have declared no conflicts of interest.