Subgroup analyses of safety and efficacy by number and types of prior lines of treatment in FRESCO-2, a global phase III study of fruquintinib in patients with refractory metastatic colorectal cancer.

Abstract

3604 Background: Effective treatment options are limited for patients (pts) with refractory metastatic colorectal cancer (mCRC). Fruquintinib (F), a highly selective, potent, oral tyrosine kinase inhibitor of VEGFR-1, -2, and -3, was evaluated in the global phase III FRESCO-2 study (NCT04322539) and demonstrated a clinically meaningful and statistically significant improvement in OS and PFS with a favorable safety profile. Here we report subgroup analyses of efficacy and safety by prior lines (PL) and types of anti-cancer treatment (Tx) for metastatic disease (MD). Methods: FRESCO-2 was conducted in the US, Europe, Japan & Australia, comparing F + best supportive care (BSC) with Placebo (P) + BSC. Pts were given 5 mg PO, QD, 3 wks on, 1 wk off, in a 28-day cycle. Eligible pts received prior chemotherapy, anti-VEGF, and if RAS wild type, anti-EGFR therapies; if BRAFV600E mutant or MSI-H, and appropriate targeted regimen; and had progressed on, or were intolerant to, trifluridine/tipiracil (TAS-102) and/or regorafenib (R). Subgroup (sbgrps) analyses for efficacy and safety were performed according to number of prior lines of tx (LOT) and by types of therapy. Results: A total of 691 pts were randomized; F:461 vs P:230. The median number of prior lines of anti-cancer tx for metastatic disease F vs P was 4 (2, 16) vs 4 (2, 12). F improved OS and PFS compared to P for all sbgrps and prior tx for MD, consistent with those of the ITT population (pop). (Table: OS reported by sbgrps and prior tx for MD). Occurrence of adverse events (AEs) and serious adverse events were generally balanced between F vs P and consistent across all subgroups. The most common ≥ G3 AEs in ≥5% of pts on F within majority of sbgrps were hypertension, asthenia and palmar plantar erythrodysesthesia and were consistent with the overall safety population. Additional analyses based on duration of prior anti-VEGF and last therapy prior to F will be presented at the conference. Conclusions: F demonstrated clinically meaningful improvement in OS, PFS with an acceptable safety profile across all sbgrps. These results were consistent with the effect observed in the overall population; irrespective of previous tx with anti-VEGF, anti-EGFR, TAS-102 and R further supporting F as a potential new tx option for pts with refractory mCRC. Clinical trial information: NCT04322539 . [Table: see text]