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MicheleMilellaIstitutoNazionaleTumoriReginaElena
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• Adjuvant Gem has been evaluated in multiple phase III trials1,2
• Adjuvant 5-FU/leucovorin is equally effective, but more toxic
a Gem was administered for only three 28-day cycles in the JSAP-02 trial vs six 28-day cycles in CONKO-001 and ESPAC-3.b Although they had similar efficacy, Gem had fewer treatment-related serious toxicities (7.5% vs 14%) than 5-FU.5-FU, 5-fluorouracil; DFS, disease-free survival; Gem, gemcitabine; HR, hazard ratio; nab-P, nab-paclitaxel; NCCN, National Comprehensive Cancer Network; Obs, observation; OS, overall survival; PC, pancreatic cancer. 1. Neoptolemos JP, et al. JAMA. 2010;304:1073-1081. 2. Neoptolemos JP, et al. Lancet. 2001;358:1576-1585. 3. Oettle H, et al. JAMA. 2007;297:267-277. 4. Oettle H, et al. JAMA. 2013;310:1473-1481. 5. Ueno H, et al. Br J Cancer. 2009;101:908-915. 6. The National Comprehensive Cancer Network. NCCN Guidelines in Oncology: Pancreatic Adenocarcinoma, v1.2013.
Adjuvant Weekly Gem at 1000 mg/m2 in Phase III Trials3-7
Trial Comparisona Primary Endpoint Median, mo HR P Value
CONKO-001 Gem vs Obs DFS 13.4 vs 6.7 0.55 < 0.001JSAP-02 Gem vs Obs OS 22.3 vs 18.4 0.77 0.19
ESPAC-3 (v2) Gem vs 5-FU/leucovorin OSb 23.6 vs 23.0 0.94 0.39
Available evidence supports adjuvantchemotherapy in operable PDAC
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Adjuvant CHT
Available evidence supports adjuvantchemotherapy inoperable PDAC
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Andit’s probably your (andpatient’s)bestbetinroutineclinical practice too…
USregistrydata(confidential information)
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5nab® is a registered trademark of Celgene Corporation.
ABI-007-PANC-003A Phase III, Multicenter, Open-Label, Randomized Study of nab®-Paclitaxel Plus Gemcitabine Versus Gemcitabine Alone as Adjuvant Therapy in Subjects With Surgically Resected Pancreatic Adenocarcinoma
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ABI-007-PANC-003 (APACT): Phase III Trial of nab-P + Gem vs Gem as Adjuvant PC TreatmentPrimary Objective
• To compare disease-free survival between patients randomized to nab-P + Gem vs Gem alone
Gem, gemcitabine; nab-P, nab-paclitaxel; PC, pancreatic cancer.ClinicalTrials.gov: NCT01964430.
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ABI-007-PANC-003 (APACT): Phase III Trial of nab-P + Gem vs Gem as Adjuvant PC TreatmentSchema
DFS, disease-free survival; EORTC, European Organisation for Research and Treatment of Cancer; Gem, gemcitabine; LN, lymph node; nab-P, nab-paclitaxel; OS, overall survival; PC, pancreatic cancer; QLQ, quality of life questionnaire; qw 3/4, first 3 of 4 weeks. 1. Celgene Data on File. Protocol ABI-007-PANC-003. 2. ClinicalTrials.gov: NCT01964430.
nab-P 125 mg/m2 qw 3/4 + Gem 1000 mg/m2 qw 3/4
× 6 cycles
Gem 1000 mg/m2 qw 3/4× 6 cycles
Confirmed resected PC with macroscopic
complete resection (R0 and R1) and no
evidence of metastases
Planned N ≈ 800
Treatment should begin within 12 weeks of surgery
Randomized 1:1
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ABI-007-PANC-003 (APACT): Phase III Trial of nab-P + Gem vs Gem as Adjuvant PC TreatmentDose Reductions
• Two dose reductions are allowed for toxicities• Patients will be discontinued from the study if further dose reductions
are required
a Dose reductions may or may not be concomitant in the nab-P + Gem arm.Gem, gemcitabine; nab-P, nab-paclitaxel, PC, pancreatic cancer.1. Celgene Data on File. Protocol ABI-007-PANC-003.
Dose Levela nab-P, mg/m2 Gem, mg/m2
Starting dose 125 1000−1 100 800−2 75 600
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ABI-007-PANC-003 (APACT): Phase III Trial of nab-P + Gem vs Gem as Adjuvant PC TreatmentSelect Inclusion Criteria
• Histologically confirmed resected PC with macroscopic complete resection (R0 and R1)
– No neuroendocrine tumors• Stage T1-3, N0-1, M0• Able to begin treatment ≤ 12 weeks after resection• Age ≥ 18 years• ECOG PS 0 or 1• Adequate hematologic and blood chemistry parameters, including
– Absolute neutrophil count ≥ 1500 cells/mm3
– Total bilirubin ≤ ULN (patients with Gilbert syndrome, ≤ 1.5 ×ULN)• CA19-9 < 100 U/mL assessed within 14 days of randomization
CA19-9, carbohydrate antigen 19-9; ECOG PS, Eastern Cooperative Oncology Group performance status; Gem, gemcitabine; nab-P, nab-paclitaxel; PC, pancreatic cancer; ULN, upper limit of normal. 1. Celgene Data on File. Protocol ABI-007-PANC-003. 2. ClinicalTrials.gov: NCT01964430.
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ABI-007-PANC-003 (APACT): Phase III Trial of nab-P + Gem vs Gem as Adjuvant PC TreatmentSelect Exclusion Criteria• Prior neoadjuvant treatment or radiation therapy or systemic therapy
for PC• Presence or history of metastatic PC• Any other malignancy within 5 years of randomization, excluding
adequately treated in situ cervical, uterus, or nonmelanomatous skin cancer
– Treatment should have been completed 6 months before randomization• Active, uncontrolled bacterial, viral, or fungal infection(s) requiring
systemic therapy• Known infection of active Hepatitis B or C• Known history of HIV or use of immuno/myelosuppressive
medications that could increase the risk of neutropenia
Gem, gemcitabine; HIV, human immunodeficiency virus; nab-P, nab-paclitaxel; PC, pancreatic cancer. 1. Celgene Data on File. Protocol ABI-007-PANC-003. 2. ClinicalTrials.gov: NCT01964430.
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ABI-007-PANC-003 (APACT): Phase III Trial of nab-P + Gem vs Gem as Adjuvant PC TreatmentStatistical Design1,2
• Assumption based on 2 previous phase III trials: Gem will result in a median DFS of 14 months1,3,4
• The estimated enrollment of this trial is 800 patients1,2
– If nab-P + Gem results in a median DFS of 19 months, this would represent an HR of 0.74
– At least 489 DFS events from 800 patients would allow 90% power to detect the HR of 0.74 at a 2-sided significance level of 0.05
DFS, disease-free survival; Gem, gemcitabine; HR, hazard ratio; nab-P, nab-paclitaxel; PC, pancreatic cancer. 1. Celgene Data on File. Protocol ABI-007-PANC-003. 2. ClinicalTrials.gov: NCT01964430. 3. Oettle H, et al. JAMA. 2007;297:267-277. 4. Neoptolemos JP, et al. JAMA. 2010;304:1073-1081
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Enrollment has been completed inMarch2016
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Italy is thetopenroller…
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Italian enrollment
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Dataanalysis is ongoing…
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APACTincontext
• ThegoalsofadjuvanttherapyaretoreducerecurrenceandimproveDFSandOSfollowingsurgeryforresectable PC
• TherearefewongoingphaseIIItrialsofadjuvanttherapyinPC
Trial No. Treatment Estimated Enrollment
NCT01013649 Gem ± radiotherapy with Cape or 5-FU N ≈ 950NCT01526135 Gem vs mFolfirinoxa N ≈ 490
NCT01150630b Neoadjuvant and adjuvant Gem ± Cis, Epi, and Cape vs adjuvant Gem N ≈ 370
Tempero MA, Cardin D, Biankin A, et al. APACT: a phase III, multicenter, open-label, randomized study of nab® -paclitaxel plus gemcitabine vs gemcitabine alone as adjuvant therapy in patients with surgically resected pancreatic adenocarcinoma. Poster presented at: American Society of Clinical Oncology Annual Meeting; May 30 - Jun 3, 2014; Chicago, IL [abstract TPS4162].
a Modified: oxaliplatin 80 mg/m2, irinotecan 180 mg/m2, folinic acid 400 mg/m2, 5-fluourouracil 1200 mg/m2/day (no bolus), q2w × 24 weeks.b Phase II/III.
5-FU, 5-fluourouracil; Cape, capecitabine; Cis, cisplatin; DFS, disease-free survival; Epi, epirubicin; Gem, gemcitabine; nab-P, nab-paclitaxel; OS, overall survival; PC, pancreatic cancer; q2w, every 2 weeks.