istical significance. At the time of the second interim OS analysis, 331 events had occurred. The co-primary endpoint of OS was met; OS was significantly improved in patients receiving KADCYLA (HR = 0.68, 95% CI: 0.55, 0.85, p = 0.0006). This result crossed the pre-specified efficacy stopping boundary (HR = 0.73 or p = 0.0037). The median duration of survival was 30.9 months in the KADCYLA arm vs. 25.1 months in the lapatinib plus capecitabine arm. See Table 8 and Figure 2.
A treatment benefit with KADCYLA in terms of PFS and OS was observed in patient subgroups based on stratification factors, key baseline demographic and disease characteristics, and prior treatments. In the subgroup of patients with hormone receptor-negative disease (n=426), the hazard ratios for PFS and OS were 0.56 (95% CI: 0.44, 0.72) and 0.75 (95% CI: 0.54, 1.03), respectively. In the subgroup of patients with hormone receptor-positive disease (n=545), the hazard ratios for PFS and OS were 0.72 (95% CI: 0.58, 0.91) and 0.62 (95% CI: 0.46, 0.85), respectively. In the subgroup of patients with non-measurable disease (n=205), based on IRC assessments, the hazard ratios for PFS and OS were 0.91 (95% CI: 0.59, 1.42) and 0.96 (95% CI: 0.54, 1.68), respectively; in patients with measurable disease the hazard ratios were 0.62 (95% CI: 0.52, 0.75) and 0.65 (95% CI: 0.51, 0.82), respectively. The PFS and OS hazard ratios in patients who were younger than 65 years old (n=853) were 0.62 (95% CI: 0.52, 0.74) and 0.66 (95% CI: 0.52, 0.83), respectively. In patients ≥ 65 years old (n=138), the hazard ratios for PFS and OS were 1.06 (95% CI: 0.68, 1.66) and 1.05 (95% CI: 0.58, 1.91), respectively.
Table 8 Summary of Efficacy from Study 1
KADCYLA
N= 495
Lapatinib +Capecitabine
N= 496
PFS: progression-free survival; OR: objective response
* Stratified by world region (United States, Western Europe, other), number of prior chemotherapeutic regimens for locally advanced or metastatic disease (0-1 vs. >1), and visceral vs. non-visceral disease. † The second interim analysis for OS was conducted when 331 events were observed and the results are presented in this table.
Progression-Free Survival
(independent review)
Number (%) of patients with event
265 (53.5%)
304 (61.3%)
Median duration of PFS (months)
9.6
6.4
Hazard Ratio (stratified*)
0.650
95% CI for Hazard Ratio
(0.549, 0.771)
p-value (Log-Rank test, stratified*)
<0.0001
Overall Survival †
Number (%) of patients who died
149 (30.1%)
182 (36.7%)
Median duration of survival (months)
30.9
25.1
Hazard Ratio (stratified*)
0.682
95% CI for Hazard Ratio
(0.548, 0.849)
p-value (Log-Rank test*)
0.0006
Objective Response Rate
(independent review)
Patients with measurable disease
397
389
Number of patients with OR (%)
173 (43.6%)
120 (30.8%)
Difference (95% CI)
12.7% (6.0,
