itinib upon RECIST-defined disease progression confirmed by blinded independent review committee (BIRC). One hundred and five (105) patients out of the 145 patients (72.4%) that discontinued treatment in the chemotherapy arm received subsequent ALK inhibitor as first antineoplastic therapy. Of these patients 81 received ceritinib.
The median duration of follow-up was 19.7 months (from randomisation to cut-off date).
The study met its primary objective demonstrating a statistically significant improvement in progression free survival (PFS) by BIRC (see Table 3 and Figure 1). The PFS benefit of ceritinib was consistent by investigator assessment and across various subgroups including age, gender, race, smoking class, ECOG performance status and disease burden.
The overall survival (OS) data was not mature with 107 deaths representing approximately 42.3% of the required events for the final OS analysis.
Efficacy data from Study A2301 are summarised in Table 3, and the Kaplan-Meier curves for PFS and OS are shown in Figure 1 and Figure 2, respectively.
Table 3 ASCEND-4 (Study A2301) - Efficacy results in patients with previously untreated ALK-positive advanced NSCLC
Ceritinib
(N=189)
Chemotherapy
(N=187)
Progression-free survival (based on BIRC)
Number of events, n (%)
89 (47.1)
113 (60.4)
Median, monthsd (95% CI)
16.6 (12.6, 27.2)
8.1 (5.8, 11.1)
HR (95% CI)a
0.55 (0.42, 0.73)
p-valueb
<0.001
Overall survivalc
Number of events, n (%)
48 (25.4)
59 (31.6)
Median, monthsd (95% CI)
NE (29.3, NE)
26.2 (22.8, NE)
OS rate at 24 monthsd, % (95% CI)
70.6 (62.2, 77.5)
58.2 (47.6, 67.5)
HR (95% CI)a
0.73 (0.50,1.08)
p-valueb
0.056
Tumour response (based on BIRC)
Overall response rate (95% CI)
72.5% (65.5, 78.7)
26.7% (20.5, 33.7)
Duration of response (based on BIRC)
Number of responders
137
50
Median, monthsd (95% CI)
23.9 (16.6, NE)
11.1 (7.8, 16.4)
Event-free rate at 18 monthsd, % (95% CI)
59.0 (49.3, 67.4)
30.4 (14.1, 48.6)
HR=hazard ratio; CI=confidence interval; BIRC=Blinded Independent Review Committee; NE=not estimable
a Based on the Cox proportional hazards stratified analysis.
b Based on the stratified log-rank test.
c OS analysis was not adjusted for the effects of cross-over.
d Estimated using the Kaplan-Meier method.
Figure 1 ASCEND-4 (Study A2301) - Kaplan-Meier curves of progression-free survival as assessed by BIRC
Figure 2 ASCEND-4 (Study A2301)- Kaplan-Meier plot of overall survival by treatment arm
Patient reported outcome questionnaires (Lung cancer symptom scale [LCSS], EORTC-QLQ-C30 [C30], EORTC QLQ-LC13 [LC13] and EQ-5D-5L) were completed by 80% or more of patients in the ceritinib and chemotherapy arms for all questionnaires at most of the time-points during the course of the study.
Ceritinib significantly prolonged time to deterioration for the pre-specified lung cancer specific symptoms of interest of cough, pain and dyspnoea (composite endpoint LCSS: HR=0.61, 95% CI: 0.41, 0.90, median Time to Deterioration [TTD] NE [95% CI: 20.9, NE] in the ceritinib arm versus 18.4 months [13.9, NE] in the chemotherapy arm; LC13: HR=0.48, 95% CI: 0.34, 0.69, median TTD 23.6 months [95% CI: 20.7, NE] in the ceritinib arm versus 12.6 months [95% CI: 8.9, 14.9] in the chemotherapy arm).
Patients receiving ceritinib showed significant improvements over chemotherapy in general Q |
