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

Zusammenfassung Hintergrund und Fragestellung Ziel dieser wissenschaftlichen Arbeit war es, Genderaspekte und Trends in Klinik, Forschung und Niederlassung in der Urologie zu analysieren. Dabei lag der Fokus auf der Objektivierung des genderspezifischen Wandels im Fachgebiet „Urologie“ zum aktuellen Zeitpunkt und in der Zukunft. Material und Methoden Es erfolgte eine digitale Umfrage bei urologischen Ärzt:innen in Deutschland über das Portal SurveyMonkey©, welche über den E‑Mail-Verteiler der Deutschen Gesellschaft für Urologie e. V. (DGU) und des Berufsverbands der Deutschen Urologen e. V. (BvDU) an alle eingetragenen Mitglieder verschickt wurde. Es wurden Basisdaten im ambulanten und stationären Sektor erhoben, sowie geschlechtsspezifische Daten in Bezug auf Arbeitsplatzverteilung, Ziele, Zufriedenheit und Gründe für berufliche Entscheidungen. Ergebnisse Die Auswertung von 398 Antworten ergab, dass urologische Kolleg:innen in der Niederlassung seltener weiblich (23,6 %) und deutlich älter (mittleres Alter 53 Jahre) waren als im stationären Sektor (Frauenanteil 47,2 %, mittleres Alter 43 Jahre). Niedergelassene Vertragsärzt:innen waren mehr Männer (49,4 %) als Frauen (29,9 %) und die Niederlassung wurde von mehr Männern als Berufswunsch angegeben (28,1 % vs. 22,8 %). Die Gründe für die Niederlassung lagen bei Frauen häufiger im familiären Bereich als bei den Männern (Hauptgründe gute Gelegenheit oder Berufswunsch). Frauen arbeiteten häufiger Teilzeit (27,0 % vs. 11,5 %) und strebten häufiger eine Karriere als Oberärztin an (29,1 % der Frauen, 9,4 % der Männer). Entsprechend war der Wunsch nach einer Habilitation oder Professur bei den Frauen häufiger als bei den Männern (20,5 % vs. 15 %). Signifikant mehr Urologinnen sahen eine Ungleichheit bei den beruflichen Aufstiegschancen (59,7 % vs. 17,5 %, p < 0,001) und 73,3 % (vs. 18,5 % der Männer, p < 0,001) empfanden ihr Geschlecht als Ursache einer Benachteiligung. Dies führte zu einer signifikant geringeren Zufriedenheit von Frauen mit ihrem beruflichen Status (p = 0,008), sowie einem geringeren Gefühl der Wertschätzung (p < 0,001). Schlussfolgerung Um die Urologie zukunftsfähig zu machen ist es essenziell, Genderaspekte noch stärker zu berücksichtigen. Der eingeschlagene Weg, der nächsten Generation von Urolog:innen ein modernes Fachgebiet zu bieten, in dem alle Ärzt:innen unabhängig von ihrem Geschlecht gerne arbeiten, wertgeschätzt werden und Chancengleichheit herrscht, sollte unbedingt weiter verfolgt und intensiviert werden, um die Urologie für die Zukunft gut aufzustellen.

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.

Background: The value of continuation of luteinizing hormone-releasing hormone (LHRH) therapy in castration-resistant prostate cancer (CRPC) remains controversial and clear evidence is lacking. Especially upon treatment with the life-prolonging cytochrome P450 17-alpha-hydroxylase/C17,20 lyase (Cyp17)-inhibitor, abiraterone, which in combination with prednisone, has the ability to further suppress testosterone serum levels over LHRH therapy alone, continuation of LHRH therapy seems to be negligible. The aim of the SPARE trial therefore was to explore the role of continuation of LHRH therapy when starting treatment with abiraterone acetate plus prednisone (AA+P) in patients with asymptomatic or mildly symptomatic, chemotherapy-naïve CPRC. Methods: Patients were randomized to receive continuing LHRH therapy versus LHRH withdrawal at the time of starting abiraterone AA+P therapy (NCT02077634). The primary endpoint was rate of rPFS at month 12. Secondary endpoints included PSA response rate, objective response, time to PSA progression and safety. Results: Altogether, 68 patients were randomized. Median age was 75 (60-86) years with a median PSA at baseline of 23.9 (0.17-1680) ng/ml. Results of the secondary endpoints were evaluated.Table: 810PLHRH+AA+PAA+PHR (p-value)Patients (n)3433Median age (range)74 (60-86) years76 (60-86) yearsMedian baseline PSA (range)31.9 (0.17-313.2) ng/ml20.59 (1.97-1680) ng/mlPSA-decline ≥50%23/34 (67.6%)24/33 (72.7%)Median treatment duration (d)2664201.667 (0.197)*study was not powered for these endpoints.Time to PSA progression (d)2883361.733 (0.188)*study was not powered for these endpoints.* study was not powered for these endpoints. Open table in a new tab Conclusions: The results of the exploratory study show that AA + P without continuation of LHRH therapy leads to considerable PSA response rates and longer time to PSA progression. The currently assessed efficacy is comparable to the results of the COU-AA-302 trial, hypothesising that continuation of LHRH therapy may not be necessary upon treatment with AA + P. Results on the primary endpoint and the safety profile are pending and are currently being evaluated. Clinical trial identification: NCT02077634. Legal entity responsible for the study: Saarland University. Funding: Janssen-Cilag. Disclosure: C. Ohlmann: Research funding: Janssen-Cilag. All other authors have declared no conflicts of interest.