V652 NIVOSWITCH: Phase II Studie - Nivolumab Erhaltungstherapie nach TKI Induktion bei Patienten mit metastasiertem Nierenzellkarzinom: Endgültige Ergebnisse der Effektivität und der Lebensqualitätsdaten (PROs)
Philipp Ivanyi, Hannover, D

Background: Tyrosine kinase inhibitors (TKI) and checkpoint inhibitors (CPI) are considered standard of care in patients (pts) with mRCC. Here, we addressed the question whether or not a 1st line switch- maintenance approach (CPI after TKI) improved outcomes in mRCC.

Methods: After 12 weeks of TKI based induction therapy 49 mRCC pts. with partial remission (PR) or stable disease (SD) were 1:1 randomized either to receive TKI continuation (n=24) or nivolumab (NIVO; 25 pts.; 240 or 480 mg IV q2-4wk). ECOG 0-2 and adequate organ function were permitted. 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. Patient-reported outcomes (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.

Results: 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. The 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).

Conclusions: A switch-maintenance approach in mRCC is not supported by our findings. A lower degree of grade ≥3 AEs for NIVO was observed, a PRO benefit was not detected. However, a major limitation of our trial is the small sample size and the selection of TKI-sensitive pts.

V497 Die sequentielle Behandlung von Patienten mit metastasiertem Nierenzellkarzinom: Analysen aus der deutschen Registerplattform CARAT
Peter J. Goebell, Erlangen, D

Introduction: Multiple novel treatments options have emerged for advanced renal cell carcinoma (mRCC) including several tyrosine kinase inhibitors (TKIs), mTOR inhibitors (mTOR), and checkpoint- inhibitors (CPIs). Here, we analysed changes in sequential treatment patterns over time since 2008. Methods: CARAT (NCT03374267) is a prospective, observational, multicentre clinical registry, which continues the preceding Tumor Registry Renal Cell Carcinoma (RCC Registry) in Germany. By April 2021, about 2084 patients (pts) in total have been enrolled with about 600 pts since the start of CARAT in 2017. Pts are recruited at start of 1st-line treatment, independent of their treatment. Details on treatments, patient and tumour characteristics, clinical and patient-reported outcomes are collected.

Follow-Up is until death or up to 3 years. For the analyses here, all pts with at least one year of follow-up (N=1477, start of treatment prior to 31/12/2019, database cut 31/12/2020) were considered.

Results: Of 1477 pts, 52% started a 2nd-line treatment, while 26% died during 1st-line treatment. For 13% 1st-line treatment was ongoing, 9% were lost to follow-up.

Pts who died prior to 2nd-line treatment were older (median 72 vs. 69 years) and more often had poor risk IMDC score (38% vs. 16%) and/or comorbidities (Charlson-Comorbidity-Index ≥1 31% vs. 21%). At the time of analysis, 69% of patients with start of treatment since 2018 were alive.

Conclusions: Sequential treatments of pts with mRCC are changing showing that novel treatment options are quickly implemented into routine care in Germany. Currently, sequential use of TKI and CPI are the preferred choice. At least a quarter of pts dies prior to receiving 2nd-line treatment highlighting an unmet medical need for this high-risk population. With longer follow-up, clinical and patient-reported outcomes will provide valuable additional evidence to guide treatment strategies in the future.


V598 Symptomatisches versus asymptomatisches Nierenzellkarzinom in Deutschland: 32-Monatsdaten der nicht-interventionellen, prospektiven VERSUS-Studie von d-uo
Manfred Johannsen, Berlin, D

Introduction: In May 2018, the German Uro-Oncologists (Deutsche Uro-Onkologen, d-uo) opened their prospective VERSUS study (VERSorgUngsStudie, VERSUS) for the documentation of outpatient diagnosis and treatment of urological tumors. This analysis addressed the question whether age and tumor stage at diagnosis differed between symptomatic vs. asymptomatic renal cell carcinoma (RCC) cases.

Methods: VERSUS is a nation-wide non-interventional, prospective, multicentric study for the documentation and evaluation of outpatient diagnosis, treatment and follow-up of urological tumors using descriptive statistics. In this analysis we evaluated patients with first diagnosis of RCC. In the d-uo database, the cause of first diagnosis (e.g. symptomatic) can be documented.

Results: Until December 2020, 7,469 patients with first diagnosis of a urological tumor were documented. Out of these, 594 patients (8%) had RCC. 70.5% were men and 29.5% were women, median age was 70.3 years (men 70.6 years and women 69.7 years). In 189 cases (31.8%, median age 68.0 years), RCC was diagnosed because of symptoms vs. 405 cases (68.2%, median age 71.2 years) without symptoms. Median Distribution of stages and gender in symptomatic vs. asymptomatic RCC cases is shown in table 1.

Conclusions: Patients with symptomatic RCC are younger and display more unfavourable tumor stages at diagnosis. This applies mainly to men, where every fourth symptomatic patient has UICC stage IV. The VERSUS study continues to collect epidemiologic and clinical data of patients with RCC.


V189 Nivolumab plus Cabozantinib (N + C) vs Sunitinib (S) bei fortgeschrittenem Nierenzellkarzinom (aRCC): Ergebnisse (stratifiziert) nach Ausgangskrankheitsmerkmalen in der Phase-3-Studie CheckMate 9ER
Jens Bedke, Tübingen, D

Introduction: First-line N+C significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) vs S in aRCC patients (pts) in the phase 3 CheckMate 9ER trial, leading to FDA approval of N+C in this setting. Assessing outcomes of N+C vs S by baseline disease characteristics can help inform clinical decision making.

Methods: Pts with clear cell aRCC were randomized to N 240 mg IV Q2W + C 40 mg PO QD vs S 50 mg PO QD (4 weeks on/2 weeks off). In this post hoc exploratory analysis, PFS, OS, and ORR were assessed across pt subgroups: IMDC risk, number of organs with ≥1 target/nontarget lesion (T/NT), sum of diameters of target lesions (sDTL), and site of metastasis (mets). PFS and ORR were evaluated per RECIST v1.1 by blinded independent central review.

Results: Median follow-up in ITT pts was 23.5 months. PFS, OS, and ORR outcomes are summarized in the Table across subgroups. PFS HR favored N+C vs S across all subgroups and median (m) PFS was longer with N+C. OS HR also favored N+C vs S across most subgroups. ORR ranged from 38%-66% (N+C) vs 10%-44% (S), and complete response benefits were seen with N+C in most subgroups.

Conclusions: Consistent with outcomes of the primary analysis, efficacy benefits with N+C vs S were maintained regardless of IMDC risk, site of mets, or extent of tumor burden at baseline, supporting N+C as a new first-line treatment option for pts with aRCC.


V471 Ansprechtiefe und Wirksamkeit unter Lenvatinib (L) + Pembrolizumab (P) und Sunitinib (S) in ausgewählten Subgruppen der CLEAR-Studie bei Patienten mit fortgeschrittenem Nierenzellkarzinom (RCC)
Viktor Grünwald, Essen, D

Introduction: In the phase 3 CLEAR study, L+P had significant PFS and OS benefits, and improved ORR vs S in 1L advanced RCC.

Methods: Pts in the CLEAR study were randomized 1:1:1 to 1 of 3 treatment arms: L 20 mg PO QD + P 200 mg IV Q3W; L 18 mg + everolimus 5 mg PO QD; or S 50 mg PO QD (4 wks on/2 wks off). We report PFS, OS, and ORR based on IMDC risk group (favorable and intermediate/poor) and presence of a target kidney lesion at baseline (post hoc analysis). Post hoc 6-month landmark analyses assessed the association between tumor shrinkage and OS. Pts who were alive at 6 months were grouped based on maximum tumor shrinkage from baseline or confirmed complete response (CR) up to 6 months. Tumor assessments were performed by independent review committee per RECIST v1.1.

Results: Among 1069 pts randomized in the CLEAR study, 355 were assigned to L+P and 357 to S. Median follow-up was 27 months for the L+P group and 26 months for the S group. PFS favored L+P (median 22.1 months, n=243) vs S (median 5.9 months, n=229) in the IMDC-intermediate/poor (HR 0.36, 95% CI 0.28-0.47) and IMDC-favorable (median 28.1 months, n=110 vs median 12.9 months, n=124; HR 0.41, 95% CI 0.28-0.62) subgroups. OS favored L+P vs S in the IMDC-intermediate/poor subgroup (HR 0.58, 95% CI 0.42-0.80); as few events were observed in the IMDC-favorable subgroup, it was inadequate to evaluate OS. ORR favored L+P vs S in the IMDC-intermediate/poor (72.4% vs 28.8%; odds ratio 6.60, 95% CI 4.39-9.90) and IMDC-favorable (68.2% vs 50.8%; odds ratio 2.00, 95% CI 1.17-3.42) subgroups. In pts with target kidney lesions, PFS, OS, and ORR were improved with L+P vs S (Table). The 6-month landmark analysis in the L+P arm showed that the OS rate at 24 months was 100% (95% CI not estimable [NE]-NE) for pts with confirmed CR, and 91.7% (95% CI 53.9-98.8) both for pts with >75% to < 100%, and 100% target-lesion reduction.

Conclusions: In pts with target kidney lesions and across evaluable IMDC subgroups, L+P conferred survival benefits vs S similar to benefits observed in the overall population. Overall, pts treated with L+P who had >75% reduction in target lesions had similar OS rates to pts with CR.