ty and efficacy of CABOMETYX for the treatment of treatment-naïve renal cell carcinoma were eva luated in a randomized, open-label, multicenter study (CABOSUN). Patients (N=157) with previously untreated, locally advanced or metastatic RCC with a clear cell component were randomized (1:1) to receive CABOMETYX (N=79) or sunitinib (N=78). Patients had to have intermediate or poor risk disease as defined by the International Metastatic RCC Database Consortium (IMDC) risk group categories. Patients were stratified by IMDC risk group and presence of bone metastases (yes/no). Approximately 75% of patients had a nephrectomy prior to onset of treatment.
For intermediate risk disease, one or two of the following risk factors were met, while for poor risk, three or more factors were met: time from diagnosis of RCC to systemic treatment < 1 year, Hgb < LLN, Corrected calcium > ULN, KPS < 80%, Neutrophil count > ULN and Platelet count > ULN.
The primary endpoint was PFS. Secondary efficacy endpoints were objective response rate (ORR) and overall survival (OS). Tumor assessments were conducted every 12 weeks.
The baseline demographic and disease characteristics were similar between the CABOMETYX and sunitinib arms. The majority of the patients were male (78%) with a median age of 62 years. Patient distribution by IMDC risk groups was 81% intermediate (1-2 risk factors) and 19% poor (≥3 risk factors). Most patients (87%) had ECOG performance status of 0 or 1; 13% had an ECOG performance status of 2. Thirty-six percent (36%) of patients had bone metastases.
A statistically significant improvement in PFS as retrospectively assessed by a blinded Independent Radiology Committee (IRC) was demonstrated for CABOMETYX compared to sunitinib (Figure 3 and Table 5). The results from the Investigator determined analysis and IRC-determined analysis of PFS were consistent.
Patients with both positive and negative MET status showed a favourable effect with CABOMETYX compared to sunitinib, with greater activity in patients with a positive MET status compared to patients with a negative MET status (HR=0.32 (0.16, 0.63) vs 0.67 (0.37, 1.23)) respectively.
CABOMETYX treatment was associated with a trend for longer survival compared to sunitinib (Table 5). The study was not powered for the OS analysis and the data are immature.
Objective response rate (ORR) findings are summarized in Table 5.
Figure 3: Kaplan Meier curve for progression-free survival by IRC in treatment-naïve RCC subjects
Table 5: Efficacy results in treatment-naïve RCC subjects (ITT population, CABOSUN)
CABOMETYX
(N=79)
Sunitinib
(N=78)
Progression-free survival (PFS) by IRC a
Median PFS in months (95% CI)
8.6 (6.2, 14.0)
5.3 (3.0, 8.2)
HR (95% CI); stratified b,c
0.48 (0.32, 0.73)
Two-sided log-rank p-value: stratified b
p=0.0005
Progression-free survival (PFS) by Investigator
Median PFS in months (95% CI)
8.3 (6.5, 12.4)
5.4 (3.4, 8.2)
HR (95% CI); stratified b,c
0.56 (0.37, 0.83)
Two-sided log-rank p-value: stratified b
p=0.0042
Overall Survival
Median OS in months (95% CI)
30.3 (14.6, NE)
21.0 (16.3, 27.0)
HR (95% CI); stratified b,c
0.74 (0.47, 1.14)
Objective Response Rate n (%) by IRC
Complete responses
0
0
Partial responses
16 (20)
7 (9)
ORR (partial responses only)
16 (20)
7 (9)
Stable disease
43 (54)
30 (38)
Progressive Disease
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