(22%). The median duration of treatment was 7.6 months (range 0.3 – 20.5) for patients receiving CABOMETYX and 4.4 months (range 0.21 – 18.9) for patients receiving everolimus.
A statistically significant improvement in PFS was demonstrated for CABOMETYX compared to everolimus (Figure 1 and Table 3). A planned interim analysis of OS was conducted at the time of the PFS analysis and did not reach the interim boundary for statistical significance (202 events, HR=0.68 [0.51, 0.90], p=0.006). In a subsequent unplanned interim analysis of OS, a statistically significant improvement was demonstrated for patients randomized to CABOMETYX as compared with everolimus (320 events, median of 21.4 months vs. 16.5 months; HR=0.66 [0.53, 0.83], p=0.0003; Figure 2). Comparable results for OS were observed with a follow-up analysis (descriptive) at 430 events.
Exploratory analyses of PFS and OS in the ITT population have also shown consistent results in favour of CABOMETYX compared to everolimus across different subgroups according to age (<65 vs. ≥65, sex, MSKCC risk group (favourable, intermediate, poor), ECOG status (0 vs. 1), time from diagnosis to randomisation (<1 year vs. ≥1 year), tumour MET status (high vs. low vs. unknown), bone metastases (absence vs. presence), visceral metastases (absence vs. presence), visceral and bone metastases (absence vs. presence), number of prior VEGFR-TKIs (1 vs. ≥2), duration of first VEGFR-TKI (≤6 months vs. >6 months).
Objective response rate findings are summarized in Table 4.
Figure 1: Kaplan Meier curve for progression-free survival by independent radiology review committee, in RCC subjects following prior vascular endothelial growth factor (VEGF)-targeted therapy (first 375 subjects randomized)
Table 3: Summary of PFS findings by independent radiology review committee in RCC subjects following prior vascular endothelial growth factor (VEGF)-targeted therapy
Primary PFS analysis Population
Intent-To-Treat Population
Endpoint
CABOMETYX
Everolimus
CABOMETYX
Everolimus
N = 187
N = 188
N = 330
N = 328
Median PFS (95% CI), months
7.4 (5.6, 9.1)
3.8 (3.7, 5.4)
7.4 (6.6, 9.1)
3.9 (3.7, .1)
HR (95% CI), p-value1
0.58 (0.45, 0.74), p<0.0001
0.51 (0.41, 0.62), p<0.0001
1 stratified log-rank test
Figure 2: Kaplan-Meier curve of overall survival in RCC subjects following prior vascular endothelial growth factor (VEGF)-targeted therapy
Table 4: Summary of ORR findings per independent radiology committee review (IRC) and investigator review, in RCC subjects following prior vascular endothelial growth factor (VEGF)-targeted therapy
Primary Analysis ORR Intent-To-Treat Population (IRC)
ORR per Investigator Review Intent-To-Treat Population
Endpoint
CABOMETYX
Everolimus
CABOMETYX
Everolimus
N = 330
N = 328
N = 330
N = 328
ORR (partial responses only) (95% CI)
17% (13%, 22%)
3% (2%, 6%)
24% (19%, 29%)
4% (2%, 7%)
p-value1
p<0.0001
p< 0.0001
Partial Response
17%
3%
24%
4%
Median time to First Response, months (95% CI)
1.91 (1.6, 11.0)
2.14 (1.9, 9.2)
1.91 (1.3, 9.8)
3.50 (1.8, 5.6)
Stable Disease as Best Response
65%
62%
63%
63%
Progressive Disease as Best Response
12%
27%
9%
27%
1 chi-squared test
Clinical data in treatment-naïve renal cell carcinoma
The safe
