Fruquintinib in less pretreated patients: Multivariate profile-matching analysis of FRESCO-2 to FRESCO

Background: In the phase 3 FRESCO (NCT02314819) and FRESCO-2 (NCT04322539) studies, fruquintinib vs placebo, plus best supportive care, significantly improved overall survival (OS) in patients with metastatic colorectal cancer (mCRC). These studies were conducted in temporally and geographically diverse populations that received distinct prior therapies; FRESCO patients were less pretreated than FRESCO-2 patients. This analysis assessed the efficacy and safety of fruquintinib in a less pretreated global population than the FRESCO-2 intention-to-treat (ITT) population. Methods: In FRESCO and FRESCO-2, patients were randomized 2:1 to receive oral fruquintinib 5 mg or matched placebo. Profile matching was undertaken using the following variables: age, Eastern Cooperative Oncology Group performance status, RAS status, number of metastatic sites, liver metastases, and number of prior treatment lines. OS, progression-free survival (PFS), and safety were assessed. Results: Of 691 patients in FRESCO-2, 152 (fruquintinib n = 103; placebo n = 49) were matched to the FRESCO ITT population. After matching, the FRESCO-2 subset and FRESCO ITT population had similar baseline characteristics and pretreatment profiles. In the FRESCO-2 subset, FRESCO ITT population, and combined dataset, respectively, unstratified hazard ratios for OS were 0.63, 0.62, and 0.63, and for PFS were 0.34, 0.27, and 0.30; 63.7 %, 61.2 %, and 61.8 % of patients had grade ≥ 3 treatment-emergent adverse events with fruquintinib. Conclusion: Clinically meaningful efficacy of fruquintinib was maintained in a global patient population with less pretreated mCRC than the FRESCO-2 ITT population, with no new safety signals, demonstrating efficacy regardless of prior treatment lines.