Efficacy, treatment modalities, and safety of regorafenib in Chinese metastatic colorectal cancer patients: A multiple centers real-world study.

Abstract

e15569 Background: For patients with refractory metastatic colorectal cancer (mCRC) treatment with regorafenib improved the overall survival (OS) in two phase 3 trials. Regorafenib has been recognized as a standard third line treatment in mCRC. However, the efficacy and safety of regorafenib in real world for Chinese patients is lacking. Methods: Patients of mCRC treated with at least one cycle of regorafenib (40, 80, 120 or 160mg OD for 21 days, as a 28-day cycle) from August 2017 to June 2020 in three Chinese medical centers were enrolled. Data of demographic, treatment, dosimetry, safety and survival was collected retrospectively. The primary endpoint was OS. Secondary endpoints were progression free survival (PFS), objective response rate (ORR), disease control rate (DCR) and the incidence of adverse events (AEs). Results: 372 patients were enrolled, of whom 266 (71.5%) accepted regorafenib alone and 106 (28.5%) received combination therapy with regorafenib. In these patients, 75 (20.16%) and 275 (73.9%) patients received regorafenib as third or higher line treatment. Starting dose was 160mg in 93 (25.0%) patients, 120mg in 74 (19.9%) patients, 80mg in 142 (38.2%) patients and 40mg in 7 (1.9%) patients. The maintenance dose was confirmed in 236 patients. Among them, 111 (46.6%) and 75 (31.8%) accepted 80 and 120mg as the last daily dose. Only 50 (21.2%) patients could receive 160mg as a long-term therapy. Median follow-up time was 15.2 months. ORR and DCR were 3.8% and 55.3%. The mPFS was 3.1 months (95%CI: 2.50-3.53) and mOS was 10.2 months (95% CI: 9.27-11.93) . The mOS of 80, 120 and 160mg last daily dose were 10.5, 14.1 and 14.3 months, respectively. Patients received regorafenib in combination with other drugs including chemotherapy or PD-1 inhibitor had longer survival compared with regorafenib alone with mOS of 15.5 (95% CI: 10.1-19.0) and 9.7 months (95% CI: 7.8-11.0) (p = 0.004). The mOS of patients developed lung metastasis and the counterpart with liver metastasis was13.3 versus 9.7 months. The common AEs were anemia (26.1%), hyperbilirubinemia (25.3%), liver injury (24.7%), thrombocytopenia (18.0%) and recorded hand-foot skin reaction (HFSR) (19.6%). The most common grade 3-4 AEs included hyperbilirubinemia (3.5%), recorded HFSR (3.5%), anemia (2.2%) and thrombocytopenia (1.1%). Due to most patients was reviewed in clinic, some data of AEs was missing or incomplete. Conclusions: In the real world, regorafenib showed promising efficacy and manageable toxicities in Chinese patients with refractory mCRC. The dose of 120mg of regorafenib seemed to have a similar survival benefit compared with 160mg. In addition to a better tolerance, 120mg may be a more suitable dose for Chinese mCRC patients. Clinical trial information: NCT04735991. [Key words] Colorectal cancer; Regorafenib; Real world