Safety of fruquintinib monotherapy and combination therapy in Chinese patients with colorectal cancer in real-world clinical practice: A subgroup analysis from phase IV study.

Abstract

e15515 Background: Although Fruquintinib (Fru) monotherapy is one of the standard treatments for third line mCRC patients(pts), combination of Fru and other anti-cancer treatments, such as chemotherapy, immunotherapy is widely used in Chinese real world clinical practice due to its synergistic or additive anticancer effect and also by potentially reducing drug resistance. A phase IV study evaluating the safety of fruquintinib in Chinese patients with mCRC demonstrated a favorable safety profile. With the increasing number of CRC patients receiving Fru therapy, it is crucial to understand its safety profile as combination therapy. This subgroup analysis of the phase IV study aims to evaluate the safety of Fru monotherapy and combination therapy in real-world setting. Methods: The data of mCRC patients were obtained from the Phase IV study (NCT04005066). Based on the treatment received, the study population was grouped into Fru monotherapy and combination therapy groups. At each follow up visit, the safety profile of the patients, including Treatment Emergent Adverse Events (TEAE) and Treatment Related Adverse Events (TRAE) was assessed and recorded. Results: A total of 2798 mCRC patients enrolled in the phase IV study between April 2019 to September 2022, received Fru administration at a dose of 5mg/day once daily for 21 days in the 28 days cycle or as determined by physicians. Fru monotherapy was administered to 1888 pts while 910 pts received combination therapy with 775 pts combined with Immune Checkpoint Inhibitor (ICI) and or chemo therapy and 135 pts combined with other anti-cancer treatment including Chinese Traditional Medicine or target therapy. For those 775pts who combined with ICI or chemo could be further divided into Fru +chemo (359 pts), Fru +ICI (493 pts), with 77 pts (Fru+ chemo + ICI) overlapped. The median treatment duration for the Fru monotherapy subgroup was 2.50 months while it was 4.70 months for the Fru + chemo+ ICI subgroup. 74.47% patients reported any grade TEAE and 23.94% reported grade ≥3 TEAE in the Fru monotherapy subgroup while 83.87% reported any grade TEAE and 26.06% reported grade ≥3 TEAE in the combination therapy group. The most common TRAEs in monotherapy and combination treatment subgroups were palmar-plantar erythrodysesthesia (PPES) (19.70% vs 22.84%) followed by hypertension (17.00% vs 16.52%). Among the Grade ≥3 TRAE, hypertension (6.73% vs 7.74%) and PPES (2.54% vs 1.81%) were the top two TRAEs in mono and combination treatment groups respectively. Conclusions: Fruquintinib demonstrated a satisfactory safety profile in monotherapy and combination therapy groups. The combination therapy groups demonstrated a longer treatment duration time, it might indicate an improved patient outcome. Clinical trial information: NCT04005066 .