García‐Alfonso, Pilar

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]

512 Background: Angiogenesis is an important therapeutic target in CRC; VEGF plays a key role in angiogenesis. RAM is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. The RAISE study evaluated the efficacy and safety of adding RAM to standard second-line treatment FOLFIRI. Methods: Eligible pts with mCRC who progressed on or after first-line combination therapy with bev, ox, and fp, had an ECOG PS of 0 or 1, and adequate organ function were randomized 1:1 (stratified by region, KRAS mutation status, and time to progressive disease [PD] after beginning first-line treatment) to receive RAM (8 mg/kg IV) plus FOLFIRI or PBO plus FOLFIRI every 2 weeks until PD, unacceptable toxicity, or death. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Planned sample size of 1,050 pts ensured 85% power to demonstrate statistical significance at an overall two-sided alpha of 0.05, assuming a hazard ratio (HR) of 0.8. Results: Between Dec 2010 and Aug 2013, 1,072 eligible pts were randomized (RAM 536; PBO 536). Baseline pt characteristics were similar between treatment arms. The OS HR was 0.84 (95% CI: 0.73, 0.98; log-rank p=0.0219). Median OS was 13.3months (m) for RAM vs 11.7m for PBO. The PFS HR was 0.79 (95% CI: 0.70, 0.90; log-rank p = 0.0005). Median PFS with RAM was 5.7m and 4.5m for PBO. ORR was 13.4% RAM; 12.5% PBO (p = 0.6336). Subgroup results were consistent with the OS and PFS results. Grade ≥3 adverse events (AEs) occurring in >5% of pts in RAM+FOLFIRI were: neutropenia (RAM 38.4% vs PBO 23.3% ), hypertension (11.2% vs 2.8%), diarrhea (10.8% vs 9.7%), and fatigue (11.5% vs 7.8%). Conclusions: RAISE met its primary end-point, demonstrating a statistically significant improvement in OS for RAM and FOLFIRI vs PBO and FOLFIRI in second-line mCRC pts. Benefits were similar across important clinical subgroups and no unexpected AEs were identified. Clinical trial information: NCT01183780.