Differential performance of immune-combinations (ICI-ICI vs ICI-TKI) in metastatic renal cell carcinoma (mRCC) with sarcomatoid features (sRCC) (Meet-URO 33 analysis).

Abstract

449 Background: The treatment landscape of mRCC has deeply evolved with the advent of 1 st line immune-combinations (ICI-ICI, ICI-TKI), but many unmet needs still remain in clinical practice. Sarcomatoid feature is a well-established negative prognostic factor but also confers sensitivity to immunotherapy. However, there are still uncertainties regarding the choice of the ICI-combinations type, warranting large-scale ad-hoc analyses. Methods: The Meet-URO 33 is an Italian multicentric retrospective/prospective observational study enrolling mRCC patients receiving 1 st line systemic therapy according to clinical practice from January 2021. Analyses on the different response and survival performance of ICI-ICI vs ICI-TKI in intermediate/poor-risk patients with sarcomatoid component (I/P-sRCC) were performed using univariate and multivariate analyses. Univariate and multivariate analyses were conducted, including also the novel prognostic Meet-URO score (IMDC + NLR + Bone metastases). Results: Among 1695 patients enrolled from 58 centres, 184 (10.9%) had sRCC, 961 (56.7%) non-sRCC and 550 (32.5%) non-assessable. Of sRCC patients, 21 patients (11.4%) were IMDC favorable-risk, 107 (58.2%) intermediate-risk and 56 (30.4%) poor-risk. In I/P-sRCC, the choice of ICI-ICI was preferred in patients with Meet-URO groups 4-5 (p = 0.018) and the choice of ICI-TKI in patients with liver and bone metastases and Meet-URO groups 2-3 (Standardized Mean Difference – SMD > 0.35). With a median follow-up of 21.8 months (mo), overall survival (OS) was longer with ICI-ICI vs ICI-TKI, while progression-free survival (PFS) and objective response rate (ORR) were comparable, although a non-statistically significant long-term trend toward improved PFS was observed (Table 1). The superiority of ICI-ICI in OS was confirmed in the multivariate analysis adjusted for the known prognostic factors (ECOG, liver/bone metastases, IMDC and Meet-URO score, histology, stage, surgery) (HR 0.47, p = 0.014). Conclusions: In the large-scale Meet-URO 33 study, I/P-sRCC patients treated with ICI-TKI had more liver and bone metastases and belonged to the more-favorable Meet-URO groups (groups 2-3). In addition, 1 st line treatment with ICI-ICI combination was associated with better long-term outcomes compared with ICI-TKI, maintaining similar response outcomes in both terms of ORR and PD. Clinical trial information: CESC IOV 2023-78. Survival Outcomes ICI-ICI ICI-TKI HR (ICI-ICI vs ICI-TKI) (95% CI) P value OS (mo) NR 23 0.58 (0.35 – 0.97) 0.04 3y-OS (%) 55.5 25.3 3y RMST OS (mo) 25.7 21.1 PFS (mo) 18.1 12.9 0.75 (0.49 – 1.15) 0.18 2y-PFS (%) 39.1 26.1 2y RMST PFS (mo) 14.4 12.6 Response Outcomes ICI-ICI ICI-TKI OR (ICI-ICI vs ICI-TKI) (95% CI) P value ORR 49.1% 50.6% 0.94 (0.47 – 1.88) 0.86 PD 20.8% 21.5% NR not reached; RMST restricted mean survival time, CI confidence interval.