Abstract
Background
Methods and Patients
Results
Conclusion
Keywords
Introduction
Patients and Methods
Study Design and Patients
Treatment
Assessment
Endpoints
Statistical Analysis
Results

Regorafenib (N = 260) | Fruquintinib (N = 106) | P | |||
---|---|---|---|---|---|
Characteristics | N | % | N | % | |
Age (years, median (range)) | 61 (21 - 89) | 59.5 (28 - 84) | .958 | ||
< 65 y | 173 | 66.5 | 70 | 66.0 | .927 |
≥ 65 y | 87 | 33.5 | 36 | 34.0 | |
Sex | .711 | ||||
Male | 154 | 59.2 | 65 | 61.3 | |
Female | 106 | 40.8 | 41 | 38.7 | |
ECOG PS | .796 | ||||
0-1 | 247 | 95.0 | 100 | 94.3 | |
2 | 13 | 5.0 | 6 | 5.7 | |
Histology | .373 | ||||
Well/moderately differentiated | 201 | 77.3 | 77 | 72.6 | |
Low differentiated/mucinous/signet ring | 48 | 18.5 | 26 | 24.5 | |
Unknown | 11 | 4.2 | 3 | 2.8 | |
Primary tumor site | .567 | ||||
Right colon | 57 | 21.9 | 24 | 22.6 | |
Left colon | 83 | 31.9 | 28 | 26.4 | |
Rectum | 120 | 46.2 | 54 | 50.9 | |
RAS mutation status | .221 | ||||
Wild-type | 128 | 49.2 | 57 | 53.8 | |
KRAS mutation | 121 | 46.5 | 42 | 39.6 | |
NRAS mutation | 4 | 1.5 | 5 | 4.7 | |
Unknown | 7 | 2.7 | 2 | 1.9 | |
BRAF V600E status | .712 | ||||
Wild-type | 233 | 89.6 | 96 | 90.6 | |
Mutation | 15 | 5.8 | 7 | 6.6 | |
Unknown | 12 | 4.6 | 3 | 2.8 | |
MMR | .574 | ||||
dMMR | 7 | 2.7 | 3 | 2.8 | |
pMMR | 239 | 91.9 | 100 | 94.3 | |
Unknown | 14 | 5.4 | 3 | 2.8 | |
Main metastatic sites at study entry | |||||
Liver | 163 | 62.7 | 64 | 60.4 | .679 |
Lung | 161 | 61.9 | 63 | 59.4 | .658 |
Lymph node | 113 | 43.5 | 34 | 32.1 | .044 |
Peritoneum | 60 | 23.1 | 23 | 21.7 | .755 |
Number of metastatic sites at study entry | .502 | ||||
1-2 | 162 | 62.3 | 70 | 66.0 | |
≥ 3 | 98 | 37.7 | 36 | 34.0 | |
Status of primary tumor at treatment start | .424 | ||||
Resected | 231 | 88.8 | 91 | 85.8 | |
Unresected | 29 | 11.2 | 15 | 14.2 | |
Time from diagnosis of metastatic disease at study start | .434 | ||||
< 18 mo | 127 | 48.8 | 47 | 44.3 | |
≥ 18 mo | 133 | 51.2 | 59 | 55.7 | |
Prior systemic anti-cancer therapy | |||||
Fluoropyrimidine | 257 | 98.8 | 105 | 99.1 | .861 |
Oxaliplatin | 242 | 93.1 | 98 | 92.5 | .833 |
Irinotecan | 221 | 85.0 | 88 | 83.0 | .635 |
Anti-VEGF antibody | 199 | 76.5 | 81 | 76.4 | .980 |
Anti-EGFR antibody | 80 | 30.8 | 29 | 27.4 | .517 |
Number of prior systemic anti-cancer therapies | .325 | ||||
1 | 57 | 21.9 | 16 | 15.1 | |
2 | 158 | 60.8 | 69 | 65.1 | |
≥ 3 | 45 | 17.3 | 21 | 19.8 |
Treatment

Efficacy

Regorafenib (N = 225) | Fruquintinib (N = 93) | |||
---|---|---|---|---|
Response | N | % | N | % |
Best of response | ||||
Complete response | 0 | 0.0 | 0 | 0.0 |
Partial response | 3 | 1.3 | 1 | 1.1 |
Stable disease | 114 | 50.7 | 52 | 55.9 |
Progressive disease | 108 | 48.0 | 40 | 43.0 |
Objective response rate | 3 | 1.3 | 1 | 1.1 |
Disease control rate | 117 | 52.0 | 53 | 57.0 |
Safety
Regorafenib n = 260 | Fruquintinib n = 106 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Any grade | ≥ Grade 3 | Any grade | ≥ Grade 3 | P-value | P-value | |||||
Adverse Events | N | % | N | % | N | % | N | % | (Any grade) | (Grade ≥3) |
Any TRAE | 221 | 85.0 | 55 | 21.2 | 84 | 79.2 | 24 | 22.6 | .180 | .754 |
Clinical adverse events | ||||||||||
HFSR | 114 | 43.8 | 18 | 6.9 | 28 | 26.4 | 4 | 3.8 | .002 | .250 |
Hypertension | 81 | 31.2 | 13 | 5.0 | 33 | 31.1 | 12 | 11.3 | .997 | .030 |
Fatigue | 41 | 15.8 | 5 | 1.9 | 15 | 14.2 | 1 | 0.9 | .696 | .829 |
Diarrhea | 26 | 10.0 | 4 | 1.5 | 8 | 7.5 | 1 | 0.9 | .463 | 1.000 |
Anorexia | 28 | 10.8 | 2 | 0.8 | 12 | 11.3 | 1 | 0.9 | .878 | 1.000 |
Weight loss | 21 | 8.1 | 0 | 0.0 | 7 | 6.6 | 0 | 0.0 | .631 | NA |
Voice changes | 19 | 7.3 | 0 | 0.0 | 3 | 2.8 | 0 | 0.0 | .102 | NA |
Rash | 15 | 5.8 | 1 | 0.4 | 5 | 4.7 | 0 | 0.0 | .688 | 1.000 |
Oral mucositis | 26 | 10.0 | 2 | 0.8 | 9 | 8.5 | 1 | 0.9 | .656 | 1.000 |
Nose bleed | 11 | 4.2 | 0 | 0.0 | 5 | 4.7 | 0 | 0.0 | .785 | NA |
Fever | 5 | 1.9 | 0 | 0.0 | 1 | 0.9 | 0 | 0.0 | .829 | NA |
Nausea/Vomiting | 12 | 4.6 | 0 | 0.0 | 4 | 3.8 | 0 | 0.0 | .940 | NA |
Muscle pain | 7 | 2.7 | 1 | 0.4 | 4 | 3.8 | 1 | 0.9 | .832 | .496 |
Colonic perforation | 3 | 1.2 | 3 | 1.2 | 2 | 1.9 | 2 | 1.9 | .959 | .959 |
Laboratory abnormalities | ||||||||||
Leukopenia/Neutropenia | 24 | 9.2 | 5 | 1.9 | 11 | 10.4 | 1 | 0.9 | .735 | .829 |
Anemia | 10 | 3.8 | 1 | 0.4 | 3 | 2.8 | 0 | 0.0 | .869 | 1.000 |
Thrombopenia | 15 | 5.8 | 3 | 1.2 | 10 | 9.4 | 1 | 0.9 | .207 | 1.000 |
ALT/AST increase | 43 | 16.5 | 5 | 1.9 | 18 | 17.0 | 2 | 1.9 | .918 | .829 |
Hyperbilirubinemia | 56 | 21.5 | 7 | 2.7 | 13 | 12.3 | 2 | 1.9 | .040 | .937 |
Proteinuria | 35 | 13.5 | 4 | 1.5 | 22 | 20.8 | 5 | 4.7 | .081 | .159 |
Treatment Sequence

Discussion
Conclusion
Clinical Practice Points
- •Precious indirect meta-analyses have showed similar efficacy and toxicity profiles of regorafenib and fruquintinib.
- •There is no randomized controlled trial directly comparing regorafenib and fruquintinib.
- •We compared regorafenib and fruquintinib, and explored the appropriate sequence in real-world set in Chinese mCRC patients.
- •The regorafenib group and the fruquintinib group showed similar efficacy, and regorafenib followed by fruquintinib showed longer overall survival than the reverse.
- •We performed propensity score-matched analysis, and subgroup analysis of single-agent therapy for sensitivity analysis, and the result did not change.
- •Most of patients received regorafenib with reduced dose, while received fruquintinib with standard dose.
- •Most AEs were similar, while any grade of HFSR and hyperbilirubinemia were more frequently observed in the regorafenib group and ≥grade 3 hypertension was more common in the fruquintinib group.
- •Regorafenib followed by fruquintinib may prolong OS over fruquintinib followed by regorafenib, and the strategy to improve the tolerance of regorafenib are desperately needed.
Compliance with Ethical Standards
Author Contributions
Data Availability Statement
Acknowledgments
Disclosure
Appendix. Supplementary materials
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