Pro: Neoadjuvant Chemoradiation for Pancreas Cancer Manisha Palta - PowerPoint PPT Presentation

Pro: Neoadjuvant Chemoradiation for Pancreas Cancer Manisha Palta Associate Professor Department of Radiation Oncology Duke University

Disclosures • Employed by Duke University • Varian: Research funding • Merck: Research funding • UptoDate: section editor author

3 Reasons in Favor of Neoadjuvant Chemoradiation • Local recurrence is common in pancreas cancer • Neoadjuvant radiation therapy facilitates a margin negative resection • Higher rates of compliance and less toxicity with neoadjuvant radiation therapy

Respecting Disease Biology

Patterns of Recurrence Study # Pts. Local Peritoneal Liver (%) (%) (%) Tepper 26 50 - - Griffin 36 53 31 44 Whittington 29 85 23 23 Ozaki 14 86 36 79 Westerdahl 74 86 - 92

Even in the modern era….. Neoptolemos Lancet 2017

Higher rates of R0 resection

Trial N Treatment Arms R0 resection Median Survival OS rate CONKO 83% 5 yr (98-04) 368 Obs 20.2 mo 10% Gem 22.8 mo 21% RTOG 9704 451 42% 5 yr (98-02) 388 5FU, CRT, 5FU 17.1 mo 18% head Gem, CRT, Gem 20.5 mo 22% ESPAC-3 84% 2 yr (07-09) 1088 5FU 23 48% Gem 23.6 49% ESPAC-4 2 yr (08-14) 732 Gem 60% 25.5 mo 52.1% Gem/Cap 28 mo 53.8% PRODIGE 3 yr (12-16) 493 Gem 60% 35 mo 48.6% FOLFIRINOX 54.4 mo 63.4%

R0 Resection is Important Neoptolemos Lancet 2017

Majority CRT R0 resection with Neoadjuvant Therapy • Meta-Analysis • 38 studies • 3484 patients • 1738 neoadjuvant therapy • R0: 66.9% (surgery 1 st ) vs. 86.8% (NAT) • Median OS: 14.8mo (surgery 1 st ) vs. 18.8mo (NAT) Versteijne BJS 2018

Preopanc RCT R0 resection: 31% (surgery 1 st ) and 63% (CRT) Van Tienhoven ASCO 2018

Preopanc Trial Van Tienhoven ASCO 2018

Phase II/III RCT Borderline Resectable Pancreas Cancer R A Upfront Surgery N Borderline Resectable Pancreas D Adenocarcinoma O (NCCN) Neoadjuvant CRT M 54Gy I Gem: 400mg/m 2, Weekly 58/110 pts Z (planned interim analysis) E Jang Ann Surgery 2018

Phase II/III RCT Borderline Resectable Pancreas Cancer CRT • R0: 26% (surgery 1 st ) vs. 52% (CRT) Upfront Surgery • Median OS: 12mo (surgery 1 st ) vs. 24mo (CRT) Jang Ann Surgery 2018

Higher rates of compliance/Less toxicity

Trial N Treatment Arms Completion Median Survival OS Adjuvant Tx CONKO 5 yr (98-04) 368 Obs 62% 20.2 mo 10% Gem 22.8 mo 21% RTOG 9704 451 5 yr (98-02) 388 5FU, CRT, 5FU 87%/86% 17.1 mo 18% head Gem, CRT, Gem 90%/88% 20.5 mo 22% ESPAC-3 2 yr (07-09) 1088 5FU 55% 23 48% Gem 60% 23.6 49% ESPAC-4 2 yr (08-14) 732 Gem 65% 25.5 mo 52.1% Gem/Cap 54% 28 mo 53.8% PRODIGE 3 yr (12-16) 493 Gem 79% 35 mo 48.6% FOLFIRINOX 66% 54.4 mo 63.4%

Compliance with Neoadjuvant CRT Trial N Treatment Arms Completion Median Survival Neoadjuvant Tx Preopanc 248 Upfront Surgery 13.7 mo CRT->Surgery 89% 17.1 mo Korea RCT 58/110 Upfront Surgery 12 mo CRT->Surgery 96% 24 mo Van Tienhoven ASCO 2018 Jang Ann Surgery 2018

Toxicity: Neoadjuvant vs. Adjuvant CRT Trial N Treatment Arms Toxicity Median Survival Preopanc 248 Upfront Surgery 13.7 mo CRT->Surgery 46% 17.1 mo RTOG 97-04 5 yr 451 5FU, CRT, 5FU 62% 18% 388 head Gem, CRT, Gem 79% 22% Van Tienhoven ASCO 2018 Regine JAMA 2008

3 Reasons in Favor of Neoadjuvant Chemoradiation • Local recurrence is common in pancreas cancer • Neoadjuvant radiation therapy facilitates a margin negative resection • Higher rates of compliance and less toxicity with neoadjuvant radiation therapy