Table 3. Cox proportional hazards models for PFS and OS with HFS as time-dependent covariate.

		Univariate		Multivariatea
End point	Time-dependent variable	Hazard ratio (95% CI)	P-value	Hazard ratio (95% CI)	P-value
PFS	HFS (yes vs no)	0.577 (0.431–0.772)	0.0002	0.558 (0.409–0.760)	0.0002
	Grade 1 HFS	0.639 (0.440–0.927)	0.0184	0.536 (0.350–0.821)	0.0042
	Grade 2 HFS	0.481 (0.321–0.720)	0.0004	0.487 (0.320–0.741)	0.0008
	Grade 3 HFS	0.641 (0.411–0.999)	0.0495	0.740 (0.466–1.178)	0.2043
OS	HFS (yes vs no)	0.417 (0.273–0.637)	<0.0001	0.436 (0.285–0.666)	0.0001
	Grade 1 HFS	0.568 (0.334–0.968)	0.0375	0.548 (0.322–0.934)	0.0270
	Grade 2 HFS	0.417 (0.227–0.765)	0.0048	0.448 (0.243–0.824)	0.0098
	Grade 3 HFS	0.220 (0.093–0.520)	0.0006	0.247 (0.104–0.586)	0.0015

Abbreviations: CI=confidence interval; HFS=hand–foot syndrome; OS=overall survival; PFS=progression-free survival.

Grade 1 HFS was defined as minimal skin changes or dermatitis (e.g., erythema) without pain; grade 2 was defined as skin changes (e.g., peeling, blisters, bleeding, oedema) or pain, not interfering with function; and grade 3 was defined as ulcerative dermatitis or skin changes with pain interfering with function.

^aSignificant baseline factors in multivariate models: Eastern Cooperative Oncology Group performance status (0 vs 1/2) in all models; oestrogen receptor/progesterone receptor status (any positive vs other) in both OS models.