Tumor shrinkage and depth of response with fruquintinib in patients with metastatic colorectal cancer: Results from FRESCO and FRESCO-2.

3555 Background: In metastatic colorectal cancer (mCRC), early tumor shrinkage (ETS) and depth of response (DpR) are predictors of overall survival (OS) and progression-free survival (PFS). Durable stable disease (SD) also reflects disease control and can contextualize PFS and OS improvements. The phase 3 FRESCO (F) and FRESCO-2 (F2) trials of fruquintinib vs placebo in patients (pts) with mCRC showed significantly longer OS (F median: 9.3 vs 6.6 months [mo], HR 0.65, P<0.001; F2 median: 7.4 vs 4.8 mo, HR 0.66, P<0.001) and PFS (F median: 3.7 vs 1.8 mo, HR 0.26, P<0.001; F2 median: 3.7 vs 1.8 mo, HR 0.32, P<0.001) with fruquintinib. We report a post-hoc analysis of tumor shrinkage (TS), ETS, and DpR, and the correlation with OS and PFS in F and F2. Methods: Pts were randomized to receive fruquintinib + best supportive care (BSC; F n=278; F2 n=461) or placebo + BSC (F n=138; F2 n=230). Tumors were assessed at screening and every 8 weeks until progressive disease (PD). TS was defined as a decrease from baseline in the sum of the longest diameters of target lesions; ETS was TS by the first post-treatment assessment; duration of TS (DTS) was time from first TS to first tumor size increase, PD, or death; in pts with best overall response of SD, duration of SD was assessed as the time from first occurrence of SD to PD/death; and DpR was the maximum percentage change from baseline in the sum of the longest diameters of target lesions. OS and PFS were assessed in pts who received fruquintinib and had TS/ETS. Results: In F, 129 (46%) fruquintinib-treated pts had TS, of which 124 (45%) achieved ETS; with placebo, 5 pts (4%) had TS and ETS. In F2, similarly, 178 (39%) fruquintinib-treated pts had TS, of which 154 (33%) achieved ETS; with placebo, 15 pts (7%) had TS and 13 pts (6%) had ETS. In pts with TS in F and F2, median DTS with fruquintinib was 1.9 and 2.0 mo, respectively. Median duration of SD was longer with fruquintinib vs placebo in both F (5.5 vs 3.7 mo) and F2 (5.6 vs 3.7 mo). Magnitude of DpR was greater with fruquintinib vs placebo in both trials. In F and F2, median OS and PFS in pts who received fruquintinib were longer in those who achieved TS and ETS vs the ITT fruquintinib arm (Table). Conclusions: ETS was observed in most fruquintinib-treated pts with TS in both F and F2 (F: 96% [124/129 pts]; F2: 87% [154/178 pts]); pts with both TS and ETS showed longer median OS and PFS compared with the fruquintinib ITT population. These data indicate that TS and ETS appear to be predictors of OS and PFS outcomes, and support the prognostic relevance of TS, ETS, and DpR in pts with mCRC. Clinical trial information: NCT02314819 and NCT04322539 . OS and PFS in pts who received fruquintinib with TS/ETS vs the ITT fruquintinib arm in F and F2. Months (95% CI) With TS With ETS ITT Fruquintinib arm F n = 129 n = 124 N = 278 OS 12.1 (10.8–14.9) 11.6 (10.7–14.9) 9.3 (8.2–10.5) PFS 5.5 (5.5–7.3) 5.5 (5.5–6.6) 3.7 (3.7–4.6) F2 n = 178 n = 154 N = 461 OS 10.9 (9.9–12.5) 10.8 (8.9–12.7) 7.4 (6.7–8.2) PFS 5.6 (5.4–6.2) 5.6 (5.1–5.8) 3.7 (3.5–3.8)