1. What do we do after FOLFIRINOX? Gemcitabine-Based Therapy is Standard
Tanios Bekaii-Saab, MD
Professor of Medicine and Pharmacy
The Ohio State University – James Cancer Hospital

2. Is There a Role for Second Line Treatment In Advanced Pancreas Cancer
A comprehensive analysis of published clinical trials show an advantage for second line therapy in pancreas cancer
Data supports 5-FU based therapy for patients with PD on gemcitabine therapy
Data supports gemcitabine-based therapy for patients with progressive disease on 5-FU ( or even gemcitabine ) based therapy

3. Gemcitabine Following 5FU
Phase II study with N=63
Primary end point = Clinical Benefit Response (CBR)
27% achieved a CBR ( median duration = 14 weeks)
mOS = 3.85 mos
Tolerable
Rothenberg ML, et al. Annals of Oncology 7: , 1996

4. Gemcitabine in combination with a platinum agent
Paclitaxol
Rahma OE, et al . Annals of Oncology 00:1-8;2013

5. Nab-paclitaxel monotherapy in pretreated patients: Phase II study
69% prior gemcitabine
5% prior FOLFIRINOX
mOS = 7.3 mos ( 95% CI, months)
mPFS = 1.7 mos ( 95% CI, mos)
1 PR and 6 SD
Hosein PJ et al. American Journal of Clinical Oncology.2013 : 36(2)

6. Nab-paclitaxel monotherapy in pretreated patient : Single institute experience
All patients had prior gemcitabine
40% had prior FOLFIRINOX
No PR; 65% SD
mPFS = 3.7 mos
mOS = 5.3 mos
Tolerable
Peddi P, et al . J Gastrointest Oncol. 2013;4(4):

7. Gemcitabine following FOLFIRINOX failure : Retrospective analysis
100 % with prior FOLFIRINOX
Median time to TF = 5 months
mOS = 5.7 mos ( 95% CI )
mPFS = 2.0 mos ( 95% CI )
Da Rocha Lino A et al . Abstract #473 – ASCO GI 2015

8. Gemcitabine plus Nab-paclitaxel in Refractory Pancreas Cancer : Single Institution Analysis
N=23 pts
Prior therapies included G, G + Oxaliplatin and FOLFIRINOX
4 PR ( including 2 pts on prior FOLFIRINOX) , 6 SD and 12 PD
mOS = 5 mos ( mos)
Zaniboni A et al. e15202 – ASCO 2014

9. Gemcitabine plus Nab-paclitaxel Following First-Line FOLFIRINOX in Refractory Pancreas Cancer : Single Institution Analysis
N=28
Med Interval from FOLFIRINOX to G + Nab-paclitaxel = 5 weeks
5 PR, 8 SD and 12 PD
OS = 23 weeks ( weeks)
TTF = 12.0 weeks ( weeks)
Median Dose Density ~ 60%
Zhang Y et al . Abstract ASCO GI 2014

10. A modified regimen of gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer
Chemotherapy
Dose
Administration
Frequency
Gemcitabine
1000 mg/m2
IVPB over 30 min
given q2weeks
Nab-paclitaxel
125 mg/m2
IVPB over 30 min
Survival analyses N
Median (months)
95% CI (months)
Progression free survival (PFS) 47
4.8
(2.6, 7.4))
Overall survival (OS)
11.1
(5.3, NR)
Toxicities
N(%)
Grades
All grades
3 / 4
Neutropenia
12 (25)
5 (10)
Febrile neutropenia
1 (2.1) --
Thrombocytopenia
9 (15)
3 (2)
Neuropathy
13 (27)
1 (2)
Fatigue
3 (6)
Krishna K et al. Abstract 366 – ASCO GI 2015

11. Capecitabine +/- Ruxolitinib (RECAP) Overall Survival
Ruxolitinib + Cape (n=64)
Placebo + Cape (n=63)
Median OS, days
136.5
129.5
Survival rate, %
3-months 64 58
6-months 42 35
12-months 22 11
HR=0.79 (95% CI: 0.53–1.18)
2-sided P=0.25
HR, hazard ratio; ITT, intent-to-treat.
Hurwitz et al. J Clin Oncol 32:5s, 2014 suppl; abstr 4000

12. RECAP: Overall Survival in Patients with CRP > 13 mg/L
Ruxolitinib + Cape (n=31)
Placebo + Cape (n=29)
Median OS, days
83.0
55.0
Survival rate, %
3-months 48 29
6-months 42 11
12-months
HR=0.47 (95% CI: 0.26–0.85)
2-sided P=0.01
Hurwitz et al. J Clin Oncol 32:5s, 2014 suppl; abstr 4000

13. RECAP : Progression-Free Survival in Patients with CRP > 13 mg/L
Ruxolitinib + Cape (n=31)
Placebo + Cape (n=29)
Median PFS, days
48.0
41.5
Survival rate, %
3-months 35 13
6-months 21 5
12-months
HR=0.62 (95% CI: 0.35–1.10)
2-sided P=0.10
PFS in patients with CRP ≤ 13 mg/L: 0.82 (95% CI: 0.47–1.41); P=0.47
Hurwitz et al. J Clin Oncol 32:5s, 2014 suppl; abstr 4000

14. Conclusions
Gemcitabine alone or gemcitabine-based combinations are considered standard of care following FOLFIRINOX failure in patients with mPCA
A modified regimen of gemcitabine + Nab-paclitaxel may be optimal if choice is made for this regimen
Phase III trials are needed to evaluate the potential benefit from gemcitabine-based therapy following FOLFIRINOX failure
JAK/Stat inhibition does not seem to produce a benefit in patients with mPCA who failed prior gemcitabine.
At best , a subgroup of patients with CRP elevation may have a marginal benefit