1. Lo sviluppo clinico di nab-paclitaxel Discussant: Nicola Silvestris
III Sessione - Il carcinoma del pancreas
Chair: C. Pinto - Moderatori: F. de Braud, A. Falcone
Lo sviluppo clinico di nab-paclitaxel Discussant: Nicola Silvestris
Studio PACT-19
Michele Reni
IRCCS Ospedale San Raffaele, Milano
• Studio PACT-19 M. Reni • Studio NABUCCO F. Di Costanzo
• Studio GAP A. Zaniboni • Studio APACT A. Bittoni
• Studio LAPACT A. Sobrero

2. PACT-19 BACKGROUND - 1
PEFG was the 1st regimen to significantly  PFS & OS over GEM in a phase III trial
GEM-nab-PTX significantly  OS over GEM in a phase III study in M+ PA
N Engl J Med Oct 31;369(18):

3. PACT-19 BACKGROUND - 2
Taxanes yield synergism with platinum compounds, GEM and fluoropyrimidines :
 intra-cellular activity of thymidine phosphorylase thus  the conversion of capecitabine into FU1
 integration of gem-triphosphate & its interaction with mRNA2
 multi-drug resistance proteins thus  cytotoxicity of DDP3
Sawada N, et al CCR 1998; 4:
Ricotti L, et al CCR 2003; 9:
Maeda S, et al Cancer Sci 2004: 95:

4. PACT-19 - OBJECTIVE
to define the RP2D of nab-PTX combined with cisplatin, capecitabine, and GEM (PAXG regimen; phase Ib study)
Secondary endpoints were OS, PFS, response rate, resection rate, toxicity

5. PAXG regimen phase I GEM (800 mg/m2 day 1, 14)
CDDP (30 mg/m2 day 1, 14)
CAPE (1250 mg/m2 day 1 to 28)
nab-paclitaxel : level mg/m2 level  mg/m2
level  mg/m2

6. PACT-19
MTD: dose at which > 2 of 3-6 pts develop DLT during the 1st month of therapy
DLT
G≥4 neutropenia lasting ≥ 7 days;
G≥3 febrile neutropenia, PLT, nausea diarrhea, or vomiting
fever ≥38.5°C, thrombocytopenia
G≥2 neurological toxicity
failure to recover to grade ≤1 toxicity or to baseline values after delaying the initiation of next cycle by > 2 weeks

7. ELIGIBILITY CRITERIA Chemo-naive patients age 18-75 yr
Karnofsky PS >70
pathological diagnosis of PA
locally advanced (stage III)
adequate baseline organ functions

8. PACT-19 BACKGROUND - 3 PDXG PEXG PEFG (n=23) (n=75) (n=59)
mOS
1yOS 74% 64% 66%
2yOS 35% 27% 20%
5yOS 17% 3% 3%

9. TRIAL POPULATION Characteristic N° (%)
Patients enrolled (Dec 12-Apr 14) 24
Median age (range) 63 (50-75)
Male 17 (71)
KPS (88)
Biliary Stent 8 (33)
Disease Site Head 17 (71)
Median CA19.9 (range) 295 (1-4591)
> ULN 19 (79)
Dose Level Level 1 3
Level 2 5
Level 3 16

10. TOXICITY Grade 3 (%) Grade 4 (%) FFX Neutropenia 29% 17% 46%
Febrile Neutropenia 0 0 5%
Platelets 0 0 9%
Hemoglobin 13% 0 8%
Nausea 4% 0 nr
Vomiting %
Diarrhea 4% 0 13%
Fatigue 17% 0 24%
Hand-foot syndrome 8% 0 0
Neuropathy 0 0 9%
Thromboembolism 0 0 7%

11. #4 – BG; 63 y

12. #9 – BR; 67 y

13. #6 – BM; 53 y

14. #10 – BA; 56 y

15. RESULTS TC N=24 PET N=21  CA19.9 N=19 LEVEL N PR SD CR >90%
>50%
100 3 2 1
125 5 -
150 16 10 6 7
TOTAL 24 17 9 8
71%
29%
43%
48% 9%
42%
53%
PDXG 23
61%
26%
56%
28%

16. RESULTS PAXG PDXG PEXG PEFG Surgery 25% 13% 15% 14% N0 80% 67% 55% 63%
mFU (12 alive)
mOS
mPFS (5 PF)
PFS-6 96% 78% 80% 81%

17. open-label, randomised, monocentric
PACT-19 - PHASE II
open-label, randomised, monocentric
Stage III and IV R
PAXG
Gem+nab-paclitaxel