ssion Free Survivala
Number of events (%) 16 (25.4) 38 (59.4)
Disease progression 12 31
Death events 4 7
Median (95% CI), months NR 5.8 (5.3, 7.9)
HR (95% CI) 0.25 (0.14, 0.45)
Overall Response Ratea 47.6% 4.7%
RESONATE-2
The RESONATE-2 study (A Randomized, Multicenter, Open-label, Phase 3 Study of the Bruton’s Tyrosine Kinase Inhibitor PCI-32765 versus Chlorambucil in Patients 65 Years or Older with Treatment-naive Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma) (NCT01722487) was conducted in patients with treatment naïve CLL or SLL who were 65 years of age or older. Patients (n = 269) were randomized 1:1 to receive either IMBRUVICA 420 mg daily until disease progression or unacceptable toxicity, or chlorambucil at a starting dose of 0.5 mg/kg on Days 1 and 15 of each 28-day cycle for a maximum of 12 cycles, with an allowance for intrapatient dose increases up to 0.8 mg/kg based on tolerability.
The median age was 73 years (range, 65 to 90 years), 63% were male, and 91% were Caucasian. Ninety one percent of patients had a baseline ECOG performance status of 0 or 1 and 9% had an ECOG performance status of 2. The trial enrolled 249 patients with CLL and 20 patients with SLL. At baseline, 20% of patients had 11q deletion. The most common reasons for initiating CLL therapy include: progressive marrow failure demonstrated by anemia and/or thrombocytopenia (38%), progressive or symptomatic lymphadenopathy (37%), progressive or symptomatic splenomegaly (30%), fatigue (27%) and night sweats (25%).
With a median follow-up of 28.1 months, there were 32 observed death events [11 (8.1%) and 21 (15.8%) in IMBRUVICA and chlorambucil treatment arms, respectively]. With 41% of patients switching from chlorambucil to IMBRUVICA, the overall survival analysis in the ITT patient population resulted in a statistically significant HR of 0.44 [95% CI (0.21, 0.92)] and 2-year survival rate estimates of 94.7% [95% CI (89.1, 97.4)] and 84.3% [95% CI (76.7, 89.6)] in the IMBRUVICA and chlorambucil arms, respectively.
Efficacy results for RESONATE-2 are shown in TABLE 18 and the Kaplan-Meier curve for PFS, assessed by an IRC according to IWCLL criteria is shown in FIGURE 3.
Table 18: Efficacy Results in Patients with CLL/SLL in RESONATE-2
Endpoint IMBRUVICA
N=136 Chlorambucil
N=133
a IRC eva luated; Five subjects (3.7%) in the IMBRUVICA arm and two subjects (1.5%) in the Chlorambucil arm achieved complete response
b HR = hazard ratio; NR = not reached
Progression Free Survivala
Number of events (%) 15 (11.0) 64 (48.1)
Disease progression 12 57
Death events 3 7
Median (95% CI), months NR 18.9 (14.1, 22.0)
HRb (95% CI) 0.16 (0.09, 0.28)
Overall Response Ratea (CR + PR) 82.4% 35.3%
P-value <0.0001
Figure 3: Kaplan-Meier Curve of Progression-Free Survival (ITT Population) in Patients with CLL/SLL in RESONATE-2
Figure 3
HELIOS
The HELIOS study (Randomized, Double-blind, Placebo-controlled Phase 3 Study of Ibrutinib, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Combination with Bendamustine and Rituximab (BR) in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lym |
