Patients and characteristics
From February 2015 through June 2018, a total of 141 eligible patients were enrolled in the parent study, and 136 patients (96%) (44, 45 and 47 in the SD, MD, and LD groups, respectively) were included in QoL analysis (Figure 1).
The characteristics of the patients in the QoL substudy are shown in Table 1. In the SD, MD and LD groups, the mean ages were 57.9, 58.4 and 57.6 years, and the mean body mass indexes (BMIs) were 25.2, 23.6 and 22.3 kg/m2, respectively, with significant differences among BMIs (P=0.03). There was no significant difference in PS, estrogen receptor status, pre-treatment by chemotherapy, pre-treatment by taxane, and comorbidities.
The response rates of questionnaire in the 2nd, 4th, and 6th courses of protocol treatment were 98%, 95% and 97% in the SD group, 98%, 100% and 97% in the MD group, and 91%, 97% and 94% in the LD group, respectively. Reasons for missing surveys are listed in Appendix Table A1.
Taxane-related QoL
Mean scores and standard deviations for FACT-Taxane, EQ-5D and CFS at each survey point are shown in Table 2. The baseline scores did not differ significantly among the groups. The mean change from baseline and 95% CI for each dose are shown in Appendix Figure A1.
In comparison of baseline-adjusted means by MMRM analysis between SD and MD, there were significant differences in FACT-Taxane TOI (overall treatment effect, P<0.001) (Figure 2). The estimated mean differences and 95% CI between SD and MD in the FACT-Taxane TOI score change from baseline in the 2nd, 4th, and 6th course of treatment were 9.8 (3.9, 15.6), 12.1 (5.9, 18.4), and 16.2 (9.7, 22.8), and the taxane-related QoL for MD was significantly better than that for SD during all observation periods. For other summary and domain scores, the estimated difference in the score change from baseline for MD was significantly higher for FACT-Taxane total (P<0.001), taxane subscale (P<0.001), PWB (P=0.002), and EWB (P=0.024). On the other hand, the SFWB score was significantly lower for MD than for SD (P=0.037) (Figure 2). Significant differences between the groups were noted, especially for the PWB and taxane subscale.
In comparison of baseline-adjusted means by MMRM analysis between SD and LD, there were significant differences in FACT-Taxane TOI (overall treatment effect, P<0.001) (Figure 2.). The estimated mean differences and 95% CI between SD and LD for the FACT-Taxane TOI score change from baseline to the 2nd, 4th, and 6th courses of treatment were 11.6 (5.8, 17.4), 15.3 (9.1, 21.4), and 16.5 (10.0, 23.0), and taxane-related QoL for LD was significantly better than that for SD during all observation periods. For other summary and domain scores, the estimated difference of the score change from baseline for LD was significantly higher for FACT-Taxane total (P<0.001), FACT-General total (P<0.011), taxane subscale (P<0.001), PWB (P<0.001), and EWB (P=0.004) (Figure 2). Significant differences between the groups were noted, especially for the PWB and taxane subscale.
In a comparison of baseline adjusted means by MMRM analysis, there were significant differences in EQ-5D utility scores between SD and MD (P=0.011), and SD and LD (P<0.001) (Figure 3). This reveals that preference-based QoL for MD and LD was also significantly better than that for SD during all observation periods.
Cancer fatigue
The mean change from baseline and 95% CI for each dose are shown in Appendix Figure A2. In comparison of baseline-adjusted means by MMRM analysis, these variables showed no significant differences at SD and MD (Figure 4). However, there were significant differences between SD and LD for CFS total score (P=0.013), and physical (P=0.001) and cognitive (P=0.033) subscores (Figure 4). The estimated mean differences and 95% CI between SD and LD in the CFS total score change from baseline to the 2nd, 4th, and 6th courses of treatment were -3.0 (-5.3, -0.8), -2.9 (-5.2, -0.5), and -3.5 (-6.0, -1.0). These data revealed that cancer fatigue for LD was significantly milder than that for SD during all observation periods.