At ESMO 2025 in Berlin, Zhenhua Liu from Chengdu, China, presented phase 3 results from the randomized, open-label FRUSICA-2 trial (NCT05522231). The talk reviewed the efficacy and safety of FRUQ+SIN versus investigator-selected AXI/EVE as second-line therapy after one prior VEGFR-TKI in advanced or metastatic RCC. This article summarizes the key data and discussion points from that presentation.
Introduction
The randomized, open-label FRUSICA-2 trial (NCT05522231) evaluated Fruquintinib plus Sintilimab against investigator-selected monotherapy (axitinib [AXI] or everolimus [EVE]) as second-line treatment for patients with locally advanced or metastatic renal cell carcinoma (RCC) previously exposed to one VEGFR-TKI. In the phase 3 readout (data cut-off Feb 17, 2025; median follow-up 16.56 months), FRUQ+SIN delivered a marked improvement in blinded independent review committee (BIRC)–assessed progression-free survival (PFS) and objective response rate (ORR), with durable responses and acceptable tolerability.
Study Design
FRUSICA-2 enrolled 234 patients (Oct 2022–Dec 2023) and randomized them 1:1 to FRUQ+SIN or AXI/EVE in 21-day cycles, stratified by ECOG performance status and IMDC risk. The primary endpoint was BIRC-assessed PFS per RECIST 1.1; key secondary endpoints included ORR, duration of response (DOR), overall survival (OS), and safety.
Population: Advanced/metastatic RCC after one prior VEGFR-TKI
Arms: 1:1, by ECOG PS and IMDC risk
- Fruquitinib+Sintilimab: FRUQ 5 mg QD (2 weeks on/1 week off) + SIN 200 mg IV Q3W
- Investigator’s choice Axitinib 5 mg BID or Everolimus 10 mg QD
Disposition: 119 to FRUQ+SIN; 115 to AXI/EVE (101 received AXI; 1 untreated)
Data cut-off: Feb 17, 2025; median follow-up 16.56 months
Results
FRUQ+SIN significantly improved efficacy vs AXI/EVE: mPFS 22.21 vs 6.90 months (HR 0.373; p<0.0001), with higher ORR 60.5% vs 24.3% and longer DOR 23.69 vs 11.33 months. Benefits were consistent across IMDC risk groups (strongest in favorable/intermediate). OS is immature (~20% events). Safety was manageable: more grade ≥3 TEAEs, but fatal TEAEs were comparable.
- Primary (BIRC PFS): 22.21 vs 6.90 mo; HR 0.373; p<0.0001
- ORR: 60.5% vs 24.3% (OR 4.622; p<0.0001)
- DOR: 23.69 vs 11.33 mo
- Subgroups: Benefit across IMDC; strongest in favorable/intermediate
- OS: Not mature (~20% data)
- Safety: ↑ grade ≥3 TEAEs; fatal TEAEs similar (4.2% vs 4.4%)
Key Take-Home Messages
- FRUQ+SIN tripled PFS vs AXI/EVE and >2× ORR, with long DOR.
- Benefits observed across IMDC risk groups, strongest in favorable/intermediate risk.
- Median DOR ~24 months supports depth and persistence of response.
- Higher grade ≥3 events with combo, but fatal TEAEs comparable to control.
- Survival data not mature; continued follow-up will clarify magnitude of OS benefit.
- For patients post-VEGFR-TKI, FRUQ+SIN represents a highly effective, tolerable option.
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