Fruquintinib Combined With PD-1 Inhibitors for the Treatment of the Patients With Microsatellite Stability Metastatic
1State Key Laboratory of Systems Medicine for Cancer, Department of Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
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.
Insights
Combining fruquintinib with PD-1 inhibitors shows promise for microsatellite stable metastatic colorectal cancer (MSS mCRC). This real-world study found a disease control rate of 55.8% and manageable side effects.
Area of Science:
- Oncology
- Immunotherapy
- Colorectal Cancer Research
Background:
- Programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors have limited efficacy in microsatellite stable (MSS) metastatic colorectal cancer (mCRC).
- Combining anti-angiogenesis and PD-1 inhibitors may enhance anti-tumour immunity in MSS mCRC by modulating the tumour microenvironment.
Purpose of the Study:
- To evaluate the clinical efficacy and safety of combining fruquintinib with PD-1 inhibitors in patients with MSS mCRC using real-world data.
- To identify potential predictive biomarkers for treatment response.
Main Methods:
- A retrospective real-world study was conducted on 77 patients with MSS mCRC treated with fruquintinib plus PD-1 inhibitors from May 2019 to March 2023.
- Clinical outcomes including partial response (PR), stable disease (SD), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were analyzed.
- Multivariate Cox analysis and immune cell analysis (PMN-MDSCs) were performed.
Main Results:
- The overall disease control rate (DCR) was 55.8% (43/77), with 5.2% achieving PR and 50.6% achieving SD.
- Median PFS was 5.1 months and median OS was 14.6 months.
- Prior treatment without vascular endothelial growth factor (VEGF) inhibitors was associated with improved PFS and OS. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) decreased post-treatment, particularly in responders.
Conclusions:
- Combination therapy of fruquintinib and PD-1 inhibitors demonstrates clinical benefit in MSS mCRC patients, especially those with lung metastases or no prior VEGF inhibitor treatment.
- Reduced PMN-MDSCs may serve as a predictive immune biomarker for this combination therapy.
- The treatment regimen was generally well-tolerated with manageable adverse events.
