32% of patients had 2 or more prior lines of metastatic therapy.
Patients received treatment until disease progression or unacceptable toxicity. The primary outcome measure was Overall Survival (OS). Additional outcome measures included Progression Free Survival (PFS) and Objective Response Rate (ORR). Results are shown in Table 4. Overall survival is illustrated in Figure 1.
Table 4: Efficacy results from NAPOLI-1 clinical study
ONIVYDE+5-FU/LV
(N= 117)
5-FU/LV
(N= 119)
Overall Survival1
Number of deaths, n (%)
75 (64)
80 (67)
Median OS (months)
6.1
4.2
(95% CI)
(4.8, 8.9)
(3.3, 5.3)
Hazard Ratio (95% CI)3
0.67 (0.49-0.92)
p-value4
0.0122
Progression-Free Survival1,2
Death or progression, n (%)
83 (71)
92 (77)
Median PFS (months)
3.1
1.5
(95% CI)
(2.7, 4.2)
(1.4, 1.8)
Hazard Ratio (95% CI)3
0.56 (0.41-0.75)
p-value4
0.0001
Objective Response Rate2
N
19
1
ORR (%)
16.2
0.8
95% CI of Rate5
9.6, 22.9
0.0, 2.5
Rate Difference (95% CI)5
15.4 (8.5, 22.3)
p-value6
< 0.0001
1 Median is the Kaplan-Meier estimate of the median survival time
2 Per RECIST guidelines, v 1.1.
3 Cox model analysis
4 Unstratified log-rank test
5 Based on Normal approximation
6 Fisher's exact test
Abbreviations: 5-FU/LV=5-fluorouracil/leucovorin; CI=confidence interval
Figure 1: Overall survival
In the limited number of patients with prior exposure to non-liposomal irinotecan, no benefit of ONIVYDE has been demonstrated.
Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with ONIVYDE in all subsets of the paediatric population in treatment of adenocarcinoma of the pancreas (see section 4.2 for information on paediatric use).
5.2 Pharmacokinetic properties
Absorption
Liposome encapsulation of irinotecan extends circulation and limits distribution relative to those of the non-liposomal irinotecan.
The plasma pharmacokinetics of total irinotecan and total SN-38 were eva luated in patients with cancer who received ONIVYDE, as a single agent or as part of combination chemotherapy, at doses between 60 and 180 mg/m2. The pharmacokinetic parameters of total irinotecan and SN-38 analytes, following the administration of ONIVYDE 80 mg/m2 are presented in Table 5.
Table 5: Summary of mean (±standard deviation) total irinotecan and total SN-38
Analyte
PK parameters
Unit
ONIVYDE geomean (95% CI)a
80 mg/m2(n=353)b
Non-liposomal irinotecan mean (SD)
125 mg/m2 (n=99)c
Total irinotecan
AUC
h ng/ml
919228
(845653-999204)
10529
(3786)
Cmax
ng/ml
28353
(27761-28958)
1492
(452)
Clearance (CL)
l/h/m2
0.087
(0.080-0.094)
13.0
(5.6)
Volume (V)
l/m2
2.6
(2.6-2.7)
138
(60.9)
t1/2 effective
h
20.8
(19.4-22.3)
6.07
(1.19)
Total SN-38
AUC
h ng/ml
341
(326-358)
267
(115)
Cmax
ng/ml
3.0
(2.9-3.1)
27.8
(11.6)
t1/2 effective
h
40.9
(39.8-42.0)
11.7
(4.29)
SD= standard deviation
AUC= area under the plasma concentration curve (extrapolated to infinity for ONIVYDE and AUC24h for non-liposomal irinotecan)
Cmax= maximum plasma concentration
t1/2 effective= effective half-lives
aValues are estimated from population PK analysis
bN=353 refers to all the subjects included in the population PK analysis
cValues are obtained from published data [Schaaf LJ et al. Clin Can |
