1. Alliance A021101: Preoperative mFOLFIRINOX + Chemoradiation in Borderline Resectable Pancreatic Cancer CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting*
May 29 - June 2, 2015
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
This program is supported by educational grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene Corporation, Genentech, Incyte, and Novartis.

2. Alliance A021101: Background
Pts with advanced pancreatic cancer often have limited survival based on incomplete resection due to involvement with mesenteric vasculature[1]
In addition, adjuvant chemotherapy delivery may be incomplete[2]
Rationale for systemic therapy and radiotherapy exist, but earlier studies in pts with borderline resectable pancreatic cancer are few
Systemic therapy: gemcitabine well tolerated, but success rate low (RR of 9%); mFOLFIRINOX with better success, but less well tolerated[3]
Radiotherapy: limited data in any other stage of localized disease
Current Alliance A pilot study sought to evaluate mFOLFIRINOX and radiotherapy as preoperative regimen for pts with borderline resectable pancreatic cancer[4]
mFOLFIRINOX; modified 5-fluorouracil, oxaliplatin, leucovorin, and irinotecan; RR, response rate.
1. Yamada S, et al. Pancreas. 2013;42: Simons JP, et al. Cancer. 2010;116: Conroy T, et al. N Engl J Med. 2011;364: Katz MHG, et al. ASCO Abstract 4008.

3. Alliance A021101: Study Design
Multicenter pilot study[1]
Primary endpoints
Accrual
Rate of preoperative treatment-related toxicity or delay
Rate of completion of all planned preoperative and operative therapy
No evidence of disease progression
Pts with borderline resectable pancreatic cancer by Intergroup definition
(N = 22)
mFOLFIRINOX
2 mos
50.4 gy EBRT +
Capecitabine
Surgery + Gemcitabine
2 mos
Criteria for Radiographic Interface Between Tumor and Vessel for Borderline Resectable[2]
Portal vein
TVI ≥ 180° and/or reconstructable occlusion
Superior mesenteric artery
TVI < 180°
Hepatic artery
Reconstructable short-segment TVI of any degree
Celiac trunk
EBRT, external beam radiation therapy; mFOLFIRINOX; modified 5-fluorouracil, oxaliplatin, leucovorin and irinotecan; TVI, tumor-vein interface.
1. Katz MHG, et al. ASCO Abstract Katz MHG, et al. Ann Surg Onc. 2013;20:

4. Alliance A021101: Baseline Characteristics
Accrual accomplished early with 13 of 14 sites enrolling ≥ 1 pt
Baseline Characteristic
All Pts
(N = 22)
Median age, yrs (range)
64 (50-76)
Male, n (%)
10 (45)
ECOG PS 0, n (%)
14 (64)
Median tumor diameter, mm (range)
30 (16-49)
Radiographic Interface in Enrolled Pts, n (%)
Total
TVI < 180
TVI ≥ 180
Portal vein
16 (73)
7 (32)
9 (41)
Superior mesenteric artery
Superior mesenteric vein
13 (59)
10 (46)
6 (27)
Hepatic artery
5 (23)
1 (5)
Celiac trunk
2 (9)
ECOG PS, Eastern Cooperative Oncology Group performance status; TVI, tumor-vein interface.
Katz MHG, et al. ASCO Abstract 4008.

5. Alliance A021101: mFOLFIRINOX Preoperative AE
Grade 3 AE in 50% of pts
Grade 4 AE: n = 1
Dose reductions of mFOLFIRINOX: n = 9 (41%)
Treatment delays: n = 10 (46%)
Median treatment delay: 1 wk (range: wks)
Treatment omissions: n = 1 (0.5%)
Event, n (%)
Grade 3
Grade 4
Dehydration
4 (18)
Diarrhea
3 (14)
Leukopenia
2 (9)
1 (5)
Thromboembolic event
Hypokalemia
AE, adverse event; mFOLFIRINOX; modified 5-fluorouracil, oxaliplatin, leucovorin and irinotecan.
Katz MHG, et al. ASCO Abstract 4008.

6. Alliance A021101: Capecitabine-XRT Preoperative AE
Capecitabine-XRT: grade 3 AEs in 36% of pts
Lymphopenia most common event: n = 3 (14%)
Other events experienced by n = 1 pt: increase in alkaline phosphatase, bilirubin, AST, or ALT; glucose intolerance; hyperglycemia; HTN; nausea; vomiting; leukopenia; paralytic ileus; metabolism disorder; nutrition disorder–other
Dose reductions: n = 1 (5%)
Treatment delay: n = 1 (5%)
Delay 1.6 wks
Treatment omissions: n = 3 (14%)
Radiation interruptions: n = 5 (24%)
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; HTN, hypertension; XRT, radiotherapy.
Katz MHG, et al. ASCO Abstract 4008.

7. Alliance A021101: Surgery, Pathology, and AEs
Among 15 pts undergoing surgery
80% (n = 12) with portal vein resection
27% (n = 4) with hepatic artery resection
R0 resection in 93%
N0 status in 67% of pathologic specimens
< 5% residual tumor cells in 47%
Complete pathologic response in 13%
1 death occurred within 90 days of surgery
Surgery Grade ≥ 3 AEs, %
Pts
(N = 15)
Anemia 38
Infection with unknown ANC 23
Infection with normal or grade 1/2 ANC 15
Surgical or postoperative hemorrhage
Anorexia
AE, adverse event; ANC, absolute neutrophil count.
Katz MHG, et al. ASCO Abstract 4008.

8. Alliance A021101: Best Preoperative Response
Best Response, n (%)
At Any Point
After mFOLFIRINOX
After Capecitabine/ XRT CR
2 (9) 2 PR
4 (18) 4 SD
14 (64) 16 11 PD
2 (9)* -- 3
Resection 15
CR, complete response; mFOLFIRINOX; modified 5-fluorouracil, oxaliplatin, leucovorin and irinotecan; PD, progressive disease; PR, partial response; SD, stable disease; XRT, radiotherapy.
*Local progression but kept on protocol, n = 1; metastases, n = 1.
Katz MHG, et al. ASCO Abstract 4008.

9. Alliance A021101: Investigator Conclusions
Small, pilot establishes feasibility of conducting intergroup study on borderline resectable pancreatic cancer
Accrual surpassed goal
Preoperative toxicity manageable
Majority of pts underwent resection (64%)
Survival data maturing
Katz MHG, et al. ASCO Abstract 4008.

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