Real world evidence from a retrospective multi-center analysis on first-line therapy for metastatic renal cell carcinoma with chromophobe histology.

488 Background: Chromophobe (chRCC) renal cell carcinoma are rare cancers and obtain a worse prognosis. We evaluated real-world treatment outcomes of 1 st line treatment in these cohort in Germany. Methods: We retrospectively analyzed patients with metastatic chRCC treated at 17 German tertiary cancer centres being treated from 2008-2023. Adverse events (AE) were reported according to CTCAE 5.0, objective response rate (ORR) according to local standard of radiological and clinical judgement. Progression free survival (PFS) and overall survival (OS) were calculated from start of treatment to progression or death, respectively and determined by KM plots. Results: We included 39 patients with a median age of 59 (IQR 55-71) years. ECOG PS was 0/1/≥2 in 70/17/12%. IMDC risk was favorable/intermediate/poor in 13/61/26%. 87% received prior nephrectomy. Lymphatic (58%), pulmonary (37%) bone (34%) and metastases were the most common metastatic sites. 52% patients received first-line IO-combinations (IO-IO: 43%, TKI-IO: 57%) and 48% patients TKI-monotherapy, predominantly sunitinib. Subsequent therapy was mostly Cabozantinib (after IO-IO), Lenvatinib/Everolimus (after IO-TKI) or Nivolumab (after TKI mono). AE of all grades occurred in 59% and 71% during IO-based therapy or TKI monotherapy, and CTCAE grade ≥3 in 29% or 25%, respectively. ORR and survival outcomes with median follow-up of 14 months (IQR 7-28) are described in the table. Conclusions: IO-combinations are frequently applied in chRCC. Our data suggests that first-line IO-/TKI-based combinations yields higher ORR compared to IO-/IO-based combinations and single agent TKI, but did not translate into an improved PFS or OS. The retrospective nature and small sample size are major limitations of our analysis. However, the rarity of metastatic chRCC contributes to inconsistent findings not only in our dataset but also across previously published studies, making it difficult to establish clear treatment guidelines. Further research is essential to refine treatment strategies for patients with metastatic chRCC. ORR and survival outcomes of study population. Parameter All therapies (n=31) IO/IO (n=8) IO/TKI (n=10) TKI (n=13) ORR (CR+PR) 19% 12,5% 30% 15% SD 16% 12,5% 40% 0% PD 65% 75% 30% 85% ORR vs. SD vs. PD - p=0.05 Parameter All therapies IO/IO IO/TKI TKI mPFS, months, 95% CI 3 (0,0-10,2) 3 (2,4-3,6) 8 (0,0-19,2) 4 (0,0-10,2) - P=0.077 mOS; months, 95% CI 24 (22,7-25,3) 12 (2,3-21,7) NR (NR-NR) 24 (22,5-25,5) - p=0.183