1. Slides: Neoadjuvant and Adjuvant Therapy
Strategies for Patients with Resectable
Pancreatic Cancer
This program is supported by educational grants from Bristol-Myers Squibb and
Ipsen Biopharmaceuticals, Inc.
2. About These Slides
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Slide credit: clinicaloptions.com
3. Faculty
Paul E. Oberstein, MD
Assistant Professor of Medicine
Division of Hematology/Medical Oncology
NYU Langone Health
Director of GI Medical Oncology
NYU Perlmutter Comprehensive Cancer Center
New York, New York
Paul E. Oberstein, MD, has disclosed that he has received consulting fees from
Genentech, Ipsen, Merck, and Rubius.
4. Pancreatic Cancer Resection Categories
Resectable
Borderline resectable
‒ Now a distinct category
‒ Neoadjuvant therapy may increase likelihood of R0 resection
Unresectable (eg, locally advanced or metastatic)
Lopez. World J Gastroenterol. 2014;20:10740. Katz. Semin Radiat Oncol. 2014;24:105. Slide credit: clinicaloptions.com
5. Neoptolemos. Lancet. 2017;389:1011.
OS
(%)
100
80
60
40
20
0
0 10 20 30 40 50 60 70 80
Mos
ESPAC-4: Adjuvant Gemcitabine ± Capecitabine in
Resected Pancreatic Cancer
Gemcitabine + capecitabine
Gemcitabine
HR: 0.82 (95% CI: 0.68-0.98; P = .032)
Median OS, Mos (95% CI)
28.0 (23.5-31.5)
25.5 (23.5-31.5)
Multicenter, randomized, open-label phase III trial (N = 732)
Slide credit: clinicaloptions.com
6. PRODIGE 24/CCTG PA.6: Adjuvant mFOLFIRINOX vs
Gemcitabine in Resected Pancreatic Cancer
Multicenter, randomized phase III trial
Slide credit: clinicaloptions.com
Conroy. NEJM. 2018;379:2395.
Primary endpoint: DFS
Secondary endpoints: toxicity, OS, cancer-specific survival, metastasis-free survival
Patients 18-79 years of age with
histologically confirmed R0 or R1
resected pancreatic ductal
adenocarcinoma; CA19-9 level
< 180 U/mL ≤ 12 wks post surgery;
ECOG PS 0/1; no prior
chemotherapy or RT (N = 493)
mFOLFIRINOX*
Q2W x 12 cycles
(n = 247†)
Gemcitabine 1000 mg/m2
Day 1, 8, 15 of 28-day cycle x 6 cycles
(n = 246‡)
*On Day 1 of each cycle, oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, and irinotecan 180 mg/m2 (reduced to 150 mg/m2 due to
20% grade 3/4 diarrhea rate in first 30 patients); continuous fluorouracil IV 2.4 g/m2 over 46 hrs. †n = 238 treated. ‡n = 243 treated.
CT scans
every 3 mos
8. APACT: Adjuvant nab-Paclitaxel Plus Gemcitabine vs
Gemcitabine in Resected Pancreatic Cancer
Multicenter, randomized, open-label phase III trial
Slide credit: clinicaloptions.com
Treatment-naive patients with
surgically resected pancreatic
cancer, ECOG PS 0/1, CA19-9 level
< 100 U/mL; within 12 wks of
surgery
(N = 866)
Continue for 6 cycles unless
disease recurrence, death,
unacceptable toxicity,
consent withdrawal, or
patient/physician decision
nab-Paclitaxel 125 mg/m2 on Days 1, 8, 15 +
Gemcitabine 1000 mg/m2 on Days 1, 8, 15
(n = 432)
Gemcitabine 1000 mg/m2 on Days 1, 8, 15
(n = 434)
28-day cycle x 6 cycles
Tempero. ASCO 2019. Abstr 4000.
Primary endpoint: DFS by independent review (first adjuvant trial in pancreatic
cancer using independently assessed DFS as the primary endpoint)
Secondary endpoints: OS, safety
9. APACT: DFS and OS
Tempero. ASCO 2019. Abstr 4000.
nab-paclitaxel + gemcitabine
Gemcitabine
HR: 0.88 (95% CI: 0.729-1.063; P = .1824)
Number of events: 439
Median DFS*, Mos
19.4
18.8
Probability
of
DFS
(%)
80
60
40
0
20
0 6 12 18 24 30 36 42 48 54
Mos
100
3 9 15 21 27 33 38 45 51
Slide credit: clinicaloptions.com
*Independently assessed.
nab-paclitaxel + gemcitabine
Gemcitabine
HR: 0.82 (95% CI: 0.680-0.996; P = .045)
Number of events: 427;
median FU: 38.5 mos
Median OS, Mos
40.5
36.2
Probability
of
OS
(%)
80
60
40
0
20
0 6 12 18 24 30 36 42 48 54
Mos
100
3 9 15 21 27 33 38 45 51 57
10. PREOPANC-1: Neoadjuvant Chemoradiotherapy vs
Immediate Surgery for Resectable Pancreatic Cancer
International, randomized, controlled phase III trial
Primary endpoint: OS (ITT)
Secondary endpoints: R0 resection rate, DFS, distant metastases–free interval,
locoregional recurrence-free interval, perioperative complications
Versteijne. JCO. 2020;38:1763.
Adult patients with
WHO PS 0/1 and
resectable* or
borderline resectable†
pancreatic cancer
(N = 246)
Gem‡
Surgery
(n = 127)
*No contact with superior mesenteric, celiac trunk, or common hepatic arteries and ≤ 90° contact with superior mesenteric portal vein.
†≥ 1 of the following required: ≤ 90° contact with superior mesenteric, celiac trunk, or common hepatic arteries or 90° to 270° contact with superior
mesenteric portal vein and no occlusion.
Gem x 6
Gem-RT Gem‡ Surgery
(n = 119)
Gem x 4
Gem: 1000 mg/m2 on Days 1, 8, 15, then 1-wk rest
‡Gem: 1000 mg/m2 on Days 1, 8, then 1-wk rest
RT: 36 Gy in 15 fractions of 2.4 Gy
All patients
followed for
12 mos
Slide credit: clinicaloptions.com
11. PREOPANC-1: Efficacy
Outcome
Preoperative
Radiochemotherapy
(n = 119)
Immediate
Surgery
(n = 127)
HR
P
Value
Median OS, mos (ITT population) 16.0 14.3 0.78 .096
Resection rate, n (%) 72 (61) 92 (72) 0.58 .058
R0 resection rate, n/N (%) 51/72 (71) 37/92 (40) 3.61 < .001
Median DFS, mos 8.1 7.7 0.73 .032
Median distant metastases–free interval, mos 17.4 12.5 0.82 .24
Median locoregional failure-free interval, mos NR 13.4 0.56 .0034
Serious AEs, n (%) 62 (52) 52 (41) 1.57 .096
Slide credit: clinicaloptions.com
Versteijne. JCO. 2020;38:1763.
12. *Resectability determined by CT or MRI of C/A/P within 28 days of registration: no interface with celiac, common hepatic, or superior mesenteric arteries; < 180° interface
with portal and superior mesenteric veins; patent portal vein/splenic vein confluence; no lesions suspicious for metastases (nodes beyond surgical basin, visceral lesions).
†5-FU 2400 mg/m2 over 46 hrs + irinotecan 180 mg/m2 + oxaliplatin 85 mg/m2. ‡Gemcitabine 1000 mg/m2 + nab-paclitaxel 125 mg/m2.
SWOG S1505: Perioperative mFOLFIRINOX vs
Gem/nab-Paclitaxel for Resectable Pancreatic Cancer
Randomized, open-label phase II trial
Sohal. JAMA Oncol. 2021:e207328. Sohal. ASCO 2020. Abstr 4504. Slide credit: clinicaloptions.com
Patients with resectable*
pancreatic adenocarcinoma;
no previous cancer therapy;
Zubrod PS 0/1
(N = 147 enrolled; n = 102
eligible and evaluable)
Gemcitabine/nab-Paclitaxel‡
Days 1,8,15 Q28D for 12 wks
(n = 47)
mFOLFIRINOX†
Q2W for 12 wks
(n = 55)
Gemcitabine/nab-Paclitaxel‡
Days 1,8,15 Q28D for 12 wks
mFOLFIRINOX†
Q2W for 12 wks
Restaging
Surgery
if
no
PD
Baseline scans underwent retrospective central radiology review for eligibility; determined that
44/147 enrolled patients ineligible for trial
Primary endpoint: 2-yr OS (“pick the winner” design: 2-yr OS for each arm first compared with
historical rate of 40%; arms compared if 2-yr OS rate ≥ 58% (power: 88%; 1-sided α = 0.05); 90%
probability of selecting OS with HR ≥ 1.4 if 50 patients/arm
13. SWOG S1505: Survival and Resection Outcomes
Study failed to meet primary endpoint (2-yr OS rate ≥ 58%)
Slide credit: clinicaloptions.com
Surgery outcomes,
n (%)
mFOLFIRINOX
(n = 40)
Gemcitabine/
nab-Paclitaxel
(n = 33)
R0 resection 34 (85) 28 (85)
Complete/moderate
pathologic response
10 (25) 13 (40)
Median no. total
nodes resected
(range)
19 (1-56) 18 (3-45)
Node-negative
resection
16 (40) 15 (45)
DFS after resection,
mos
10.9 14.2
Sohal. JAMA Oncol. 2021:e207328. Sohal. ASCO 2020. Abstr 4504.
OS
OS
(%)
Mos After Registration
mFOLFIRINOX
Gem/nab-P
At Risk
55
47
2-Yr
OS
47%
48%
mOS
23.2 mos
23.6 mos
48
0 6 12 18 24 30 36 42
100
80
60
40
20
0
mFOLFIRINOX
Gemcitabine/nab-paclitaxel
+
+ + +
+ + +
+
+
+
+
+
++
+
+
++ +
+
+
++
+ +
+
++
14. Alliance A021501: Neoadjuvant mFOLFIRINOX With or
Without RT in Borderline Resectable Pancreatic Cancer
Multicenter, randomized phase II trial
Slide credit: clinicaloptions.com
Katz. ASCO GI 2021. Abstr 377.
Primary endpoint: binary 18-month OS rate
Key secondary endpoints: EFS, safety, R0 resection rate, pCR rate
Adult patients with
borderline resectable
pancreatic
adenocarcinoma;
ECOG PS 0/1
(N = 126)
mFOLFIRINOX
4 cycles
mFOLFIRINOX
4 cycles
Restage
mFOLFIRINOX
4 cycles
mFOLFIRINOX
3 cycles + RT
Restage
Surgery
Surgery
Restage
FOLFIOX
4 cycles
FOLFOX
4 cycles
15. Alliance A021501: OS and EFS
Slide credit: clinicaloptions.com
Katz. ASCO GI 2021. Abstr 377.
Outcome
mFOLFIRINOX
(n = 65)
mFOLFIRINOX + RT
(n = 55)
OS
Events 35 40
Median OS, mos 29.8 17.1
18-mo OS rate, % 66.4 47.3
EFS
Events 45 44
Median EFS, mos 15.0 10.2
16. Ongoing Trials of Interest in the Neoadjuvant and
Adjuvant Settings
Slide credit: clinicaloptions.com
Trial Phase Treatment Notes
NCT03941093 III
Gem + nab-paclitaxel ±
pamrevlumab (anti-CTGF Ab)
Unresectable, locally advanced
disease
Alliance A021806
(NCT04340141)
III
Perioperative vs adjuvant
FOLFIRINOX
Resectable disease
PANDAS-PRODIGE 44
(NCT02676349)
II
Neoadjuvant mFOLFIRINOX ±
CRT
Borderline resectable disease
17. clinicaloptions.com/oncology
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