Efficacy comparison of fruquintinib, regorafenib monotherapy or plus programmed death-1 inhibitors for microsatellite stable metastatic colorectal cancer

Table 5 Univariate and multivariate analyses of risk factors for progression-free survival and overall survival

All patients	Progression-free survival						Overall survival
	Univariate analysis			Multivariate analysis			Univariate analysis			Multivariate analysis
	HR	95%CI	P value	HR	95%CI	P value	HR	95%CI	P value	HR	95%CI	P value
Age (< 65/≥ 65 yr)	0.764	0.533-1.095	0.143				1.054	0.713-1.558	0.791
Sex (female/male)	0.713	0.552-0.923	0.010	0.587	0.447-0.771	< 0.001a	0.755	0.556-1.024	0.071
Primary tumor location (left/right)	1.123	0.826-1.527	0.460				1.162	0.815-1.657	0.407
Baseline ECOG (0/1)	1.434	0.931-2.207	0.102				1.426	0.893-2.278	0.137
RAS mutation status (wild/mutant)	1.058	0.886-1.262	0.536				1.001	0.808-1.240	0.992
BRAF mutation status (wild/mutant)	1.034	0.888-1.204	0.664				1.127	0.946-1.342	0.180
Status of primary tumor (unresected/resected)	0.728	0.529-1.002	0.051	0.815	0.583-1.141	0.233	0.696	0.478-1.012	0.058	0.882	0.591-1.318	0.540
Liver metastasis (no/yes)	1.591	1.221-2.071	0.001a	1.796	1.353-2.383	< 0.001a	1.843	1.344-2.527	< 0.001a	1.645	1.184-2.285	0.003a
Lung metastasis (no/yes)	0.994	0.766-1.290	0.963				0.729	0.538-0.988	0.042a	0.705	0.511-0.973	0.033a
Number of metastatic sites (</≥ 3)	1.350	1.035-1.762	0.027a	1.181	0.893-1.562	0.244	1.726	1.267-2.350	0.001a	1.714	1.235-2.378	0.001a
Prior treatment lines (2/> 2)	1.270	0.976-1.653	0.075				1.094	0.800-1.494	0.575
Irinotecan (no/yes)	1.833	1.157-2.905	0.010a	1.625	0.976-2.707	0.062	1.586	0.900-2.794	0.111
Oxaliplatin (no/yes)	0.656	0.388-1.108	0.115				0.859	0.438-1.683	0.657
Prior treatment with VEGF (no/yes)	1.640	1.122-2.398	0.011a	1.747	1.133-2.692	0.011a	1.617	1.018-2.568	0.042a	1.709	1.068-2.734	0.026a
Prior treatment with EGFR (no/yes)	1.281	0.921-1.781	0.141				1.264	0.866-1.844	0.225
Regimen (The F group as the reference)
R	0.928	0.632-1.363	0.702				0.917	0.564-1.491	0.727
Regimen (the R group as the reference)
RP	1.145	0.787-1.666	0.479				1.474	0.966-2.250	0.072	1.517	0.744-1.801	0.518
Regimen (the FP group as the reference)
F	1.400	0.979-2.001	0.065	1.399	0.974-2.010	0.070	1.012	0.640-1.600	0.959
RP	1.487	1.052-2.103	0.025a	1.470	1.030-2.097	0.034a	1.369	0.920-2.035	0.121

^aP < 0.05, and the difference is statistically significant.

F: Fruquintinib; R: Regorafenib; FP: Fruquintinib plus programmed death-1 inhibitors; RP: Regorafenib plus programmed death-1 inhibitors; HR: Hazard ratio; ECOG: Eastern cooperative oncology group.