Real world evidence from a retrospective multi-center analysis on first-line therapy for metastatic renal cell carcinoma with non-clear cell and/or sarcomatoid histologies

• Published in: Journal of clinical oncology Vol. 42; no. 4_suppl; p. 392
• Main Authors: Zschaebitz, Stefanie, Casuscelli, Jozefina, Rinderknecht, Emily, Mattigk, Angelika, Gür, Melis, Ivanyi, Philipp, Hilser, Thomas, Darr, Christopher, Mandal, Subhajit, Schlack, Katrin, Seidl, Daniel, Handke, Analena, Klee, Melanie, Nestler, Tim, Rehlinghaus, Marc, Hijazi, Sameh, Heidenreich, Axel, Grünwald, Viktor, Schostak, Martin
• Format: Journal Article
• Language: English
• Published: American Society of Clinical Oncology 01.02.2024
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2024.42.4_suppl.392

392Background: Papillary (pRCC), chromophob (chRCC) and predominantly sarcomatoid renal cell carcinoma (sRCC) as well as RCC with sarcomatoid features are rare cancers. We evaluated real-world treatment outcomes of 1st line treatment in these cohorts in Germany. Methods: We retrospectively analyzed patients with non-clear cell RCC treated at 17 German tertiary cancer centres. Adverse events (AE) were reported according to CTCAE 5.0, objective response rate (ORR) according to RECIST 1.1. 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 189 patients with a median age of 63 years (IQR 54-72). Of these, 49% were pRCC, 12% chRCC, 12% sRCC. 17% of all RCC had a sarcomatoid features. 87% had an ECOG PS of 0/1. IMDC risk was favorable/intermediate/poor in 15/54/31%. 74% received prior nephrectomy. Lymphatic (63%) and pulmonary (51%) metastases were the most common metastatic sites. 72% patients received first-line IO-combinations (IO-IO: 36%, TKI-IO: 64%) and 28% patients TKI-monotherapy, predominantly sunitinib. AE of all grades occurred in 86% and 72% during IO-based therapy or TKI monotherapy, and CTCAE grade ≥ 3 in 46% or 36%, of which led to discontinuation of treatment in 42% or 29% of patients, respectively. ORR and survival outcomes with median follow-up of 17 months (IQR 9-30) are described in the table. Conclusions: IO-combinations are frequently applied in pRCC, chRCC and sRCC. Our data suggests that first-line IO-combinations yields higher ORR compared to single agent TKI in sRCC, but not in chRCC. However, the retrospective nature and small sample size are major limitations of our analysis. Additional analyses to tailor treatment strategies in patients with metastatic nccRCC or sRCC is warranted. ParameterpRCC (n=70)chRCC (n=17)sRCC + sarcomatoid features (n=38)TKI n=29IO n=41TKI n=4IOn=13TKI n=4IOn=34ORR (CR+PR)38%46%50%31%0%59%SD34%32%25%23%25%15%PD28%22%25%46%75%26%ORR vs. SD vs. PDp=0.867p=0.007p=0.072ParameterpRCC (n=92)chRCC (n=19)sRCC + sarcomatoid features (n=38)TKI n=37IO n=55TKI n=6IOn=13TKI n=4IO n=34mPFS, months, 95% CI7 (5.2-8.8)3 (0.2-5.8)4 (2.5-5.5)8 (4.9-11.1)6 (4.2-7.7)10 (4.9-15.1)1 (NA)2 (NA)4 (2.8-5.2)mOS;months, 95% CI34 (23.2-44.8)28 (21.7-34.3)34 (11.3-56.7)38 (19.7-56.8)32 (16.6-47.4)24 (7.0-41.0)28 (17.5-38.5)22 (0-52.4)not reached