Fruquintinib Combined With PD-1 Inhibitors for the Treatment of the Patients With Microsatellite Stability Metastatic Colorectal Cancer: Real-World Data

Abstract

Aims: Programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors have shown limited effectiveness in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Combining anti-angiogenesis inhibitors with PD-1 inhibitors has the potential to reverse the immunosuppressive tumour microenvironment, synergistically enhancing the anti-tumour immune response in MSS mCRC. The goal is to present real-world data that prove the clinical efficacy and safety of fruquintinib combined with PD-1 inhibitors in MSS mCRC.

Materials and methods: We conducted a real-world retrospective study in patients with MSS mCRC who received treatment with fruquintinib combined with PD-1 inhibitors between May 2019 and March 2023 in our centre.

Results: Seventy seven patients with MSS mCRC received fruquintinib combined with PD-1 inhibitors. In total, 5.2% of patients (4/77) achieved a partial response (PR), while 50.6% (39/77) had a stable disease (SD). Notably, three lesions achieving PR were all lung metastases and the overall disease control rate (DCR) reached 55.8% (43/77). Median progression-free survival (PFS) and overall survival (OS) reached 5.1 months (95% CI: 3.6-6.7) and 14.6 months (95% CI: 9.6-15.6), respectively. Multivariate Cox analysis showed that prior treatment without vascular endothelial growth factor (VEGF) inhibitors was significantly associated with PFS and OS (p < 0.05). Further analysis indicated that total- or polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) significantly decreased after treatment (P = 0.039), especially in the PR/SD group (P = 0.003). Most adverse events included abdominal pain, rash, oedema, diarrhoea, and immunotherapy-associated hypothyroidism, yet symptoms were controllable.

Conclusion: Our results provided additional evidence that patients with MSS mCRC could benefit from the combination of fruquintinib and PD-1 inhibitors, especially those with lung metastases or without prior treatment with VEGF inhibitors. The detection of MDSCs may be an immune indicator for predicting of the combined therapy.

Keywords: Fruquintinib; PD-1 inhibitors; metastatic colorectal cancer; microsatellite stability; real-world data.