Bianchi, Andrea Sartore

142 Background: Fruquintinib (F) is a highly selective, oral tyrosine kinase inhibitor of all 3 vascular endothelial growth factor receptors (VEGFRs -1, -2, -3) that is approved by the US FDA and in the EU, UK, and Japan for previously treated metastatic colorectal cancer (mCRC), regardless of biomarker status. FRESCO-2 (NCT04322539) met its primary endpoint demonstrating significantly improved overall survival (OS) with F + best supportive care (BSC) vs placebo (P) + BSC. This subgroup analysis assessed landmark survival of all FRESCO-2 patients (pts), and baseline (BL) characteristics and safety data of pts treated with F who had OS ≥10 months (mos) compared with the intent-to-treat (ITT) population (pop). Methods: Pts were randomized 2:1 to receive F 5 mg or matching P, by mouth, once daily, 3 weeks on, 1 week off, + BSC. Pts had received prior chemotherapy, anti-VEGF therapy and, if RAS wild type, anti-EGFR therapy; and had prior exposure to trifluridine/tipiracil (TAS-102) and/or regorafenib. The hazard ratio (HR) between the two treatment arms was calculated from a stratified Cox proportional hazard model with treatment group as the only covariate in the model. Results: In the ITT pop, OS was improved with F vs P (HR 0.66); OS rates (95% confidence intervals [CIs]) at 6 and 9 mos were 60.4% (55.9–64.9) vs 41.5% (35.0–48.0) and 41.1% (36.4–45.8) vs 28.2% (22.1–34.3), respectively. Progression-free survival (PFS) rates (95% CIs) at 6 and 9 mos were 23.8% (19.7–28.0) vs 1.1% (0–2.6) and 11.3% (8.1–14.6) vs 0.5% (0–1.6), respectively. Of 461 pts who received F, 113 (24.5%) had OS ≥10 mos (range 10.0–18.9) with a median duration of F treatment of 6.3 mos (range 0.7–19.1). Among pts receiving F, a higher proportion (≥10% difference) of pts with OS ≥10 mos had no liver metastases (mets) and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 at BL compared with the ITT pop (Table). In pts with OS ≥10 mos, 61.9% experienced a grade ≥3 treatment-emergent adverse event compared with 62.7% in the ITT pop. Conclusions: Longer-term OS and PFS rates at 6 and 9 mos were higher with F vs P in the FRESCO-2 ITT pop. The data show a higher proportion of pts with OS ≥10 mos had an absence of liver mets and ECOG PS 0 at BL than the ITT pop. The safety profile of F in pts with OS ≥10 mos was consistent with the ITT pop. Clinical trial information: NCT04322539 . BL characteristics of pts treated with F with OS ≥10 mos vs ITT pop. BL characteristic Pts with OS ≥10 mos (n=113) ITT pop(n=461) ECOG PS (0 / 1), % 54.0 / 46.0 42.5 / 57.5 Median time since 1 st CRC diagnosis, mos 52.0 47.2 Primary tumor location at 1 st diagnosis (colon / rectum / both), % 51.3 / 35.4 / 13.3 60.5 / 31.0 / 8.5 Primary site at 1 st diagnosis (colon left / colon right), % 42.5 / 15.9 41.6 / 21.0 Liver mets, % 58.4 73.5 Median duration of mCRC, mos 42.7 37.9 Prior lines of therapy for mCRC (≤3 / >3), % 26.5 / 73.5 27.1 / 72.9 Prior TAS-102, % 46.9 52.1 Prior regorafenib, % 12.4 8.7

3579 Background: Fruquintinib (F) is a highly selective, oral tyrosine kinase inhibitor of all 3 VEGF receptors. Based on FRESCO (NCT02314819) and FRESCO-2 (NCT04322539) data, F was approved by the US FDA for previously treatedmetastatic colorectal cancer (mCRC). Efficacy and safety of F + best supportive care (BSC) vs placebo (P) + BSC were analyzed according to prior treatment (tx) sequence using FRESCO and FRESCO-2 data. Methods: In FRESCO and FRESCO-2, patients (pts) were randomized 2:1 to receive F 5 mg or matching P, PO daily x 21 days every 28 days. In FRESCO, eligible pts had received ≥2 prior chemotherapy regimens and were permitted to have received prior anti-VEGF and/or anti-EGFR therapies, whereas in FRESCO-2, in addition to standard chemotherapies, anti-VEGF, and anti-EGFR therapies if indicated, prior exposure to trifluridine/tipiracil (TAS) and/or regorafenib (rego) was required. FRESCO-2 pts must have also received a BRAF inhibitor and/or immunotherapy, if indicated and available in their country. Results: In FRESCO (F n=278 vs P n=138), no pts had received rego and 16/416 pts (4%) had received TAS. InFRESCO-2, prior therapies were balanced between F vs P arms; pts had received prior TAS or rego in these sequences: prior TAS only (n=240 vs n=121); prior rego only (n=40 vs n=18); prior rego then TAS (n=84 vs n=45); prior TAS then rego (n=95 vs n=44). Improvements in OS and PFS were seen with F vs P regardless of prior tx sequence (Table), with similar magnitudes of benefit for OS (HRs 0.53–0.77) and PFS (HRs 0.25–0.37). F safety profile was consistent regardless of prior tx sequence (Table). Conclusions: F is effective in mCRC with a manageable safety profile regardless of prior TAS or rego tx and sequence. Improvement with F was similar for OS and PFS despite the number and sequence of prior regimens. F provides a new tx option for pts with previously treated mCRC regardless of prior TAS or rego exposure. Clinical trial information: NCT04322539 . [Table: see text]