KEY TAKEAWAYS
- The Regosinti phase II trial aimed to evaluate the combined efficacy of regorafenib and immune checkpoint inhibitors.
- The primary endpoint was to measure OS. Secondary endpoints included measuring PFS, ORR, DCR, and safety.
- The study found that the R+S combination for mCRC showed promising results with a manageable safety profile.
Regorafenib can boost anti-tumor immunity by reducing tumor-associated macrophages (TAMs) and other immunosuppressive cells. This works synergistically with anti-PD-1/PD-L1 antibodies in microsatellite stable (MSS) or mismatch repair (MMR)-proficient colorectal cancer (CRC).
Researchers aimed to evaluate the combined efficacy of regorafenib and immune checkpoint inhibitors. The study determined the combined dose of Regorafenib (R) (80mg QD 3 weeks/4) + Sintilimab(S) (200mg every 3 weeks) for non-MSI-H metastatic colorectal cancer(mCRC) patients (pts). The Primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety.
Around 103 mCRC pts received R+S with a median age of 57 (range 28-75). Male 59.2%, ECOG PS 0/1/2 20.4%/66.0%/13.6%, left-sided colon/right-sided colon/rectum 39.8%/15.5%/44.7%, RAS mutant 42.7%. ORR 21.4%, DCR 63.1%, cCR 1 (1.0%), PR 21 (20.4%), SD 43 (41.7%). The median follow-up was 19.9 months(range 0.1-41.4). The median PFS was 4.0 months (95% CI 3.1-4.4 months), while the median OS was 13.0 months (95% CI 12.0-16.5 months). ORR pts had significantly longer PFS (20.8 vs. 3.2 months, P< 0.001) and OS (not reached vs. 12.0 months, P< 0.001) than non-ORR pts. Median PFS was consistent across KRAS mutation status, primary sidedness, or liver metastases. Multivariate analysis revealed worse OS association with male gender, ECOG PS2, ≥2 metastatic sites, and RAS mutation. Common grade 3/4 adverse events(AEs) included hand-foot syndrome (1.9%), stomatitis (1.9%), rash (1.0%), hypertension (1.0%), allergic reaction (1.0%), fatigue (1.0%), and fever (1.0%). Treatment modifications affected 8 (7.8%) pts. No treatment-related deaths occurred.
The study found R+S combination for mCRC showed promising results with a manageable safety profile. Female, ECOG PS0/1, single metastases, RAS wild type mCRC had better OS.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.3562
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04745130
Rui Liu, Zhi Ji, Xia Wang, Le Zhang, Yuchong Yang, Tao Ning, Shaohua Ge, Hongli Li, Ming Bai, Ting Deng, and Yi Ba. DOI: 10.1200/JCO.2023.41.16_suppl.3562 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 3562-3562
