Neoadjuvant Chemotherapy
JORDAN BERLIN, MD
DISCLOSURES
• Advisory Boards here and there in last year or so– Genentech/Roche– Celgene– FivePrime– EMD Serono– Arno– Gritstone– Erytech– Abbvie– Nestle– Astra Zeneca– Eisai
• Current Research Support– Novartis (Array) , Abbvie,
Immunomedics,, Taiho, Genentech/Roche, Bayer, Incyte, Pharmacyclics, FIvePrime, Loxo, EMD Serono, PsiOxus,
• DSMB– Astra Zeneca
ADJUVANT VS NEOADJUVANT
• Pancreas cancer is a systemic disease upon presentation– 10% of patients survive
10 years with surgery alone
• Highest response rates available are for chemotherapy– Still only 31% for
FOLFIRINOX
• Goal of adjuvant and neoadjuvant therapy is to kill micrometastaticdisease– Best “kill” is when it is
smallest (presentation, not post-op)
– In a study of patients in Ontario, Canada only 75% of resected patients even received adjuvant gemcitabine*
• But now our standard has moved past gemcitabine
*Kagedan, et al Curr Oncol 334-42, 2016 23:
PRODIGE 24/CCTG PA.6, AN UNICANCER GI TRIAL: A MULTICENTER INTERNATIONAL RANDOMIZED PHASE III TRIAL OF ADJUVANT MFOLFIRINOX VERSUS GEMCITABINE (GEM) IN PATIENTS WITH RESECTED PANCREATIC DUCTAL ADENOCARCINOMAS.
Presented By Thierry Conroy at 2018 ASCO Annual Meeting
SLIDE 3
Presented By Thierry Conroy at 2018 ASCO Annual Meeting
DISEASE-FREE SURVIVAL
Presented By Thierry Conroy at 2018 ASCO Annual Meeting
SLIDE 21
Presented By Thierry Conroy at 2018 ASCO Annual Meeting
PREOPERATIVE RADIOCHEMOTHERAPY VERSUS IMMEDIATE SURGERY FOR RESECTABLE AND BORDERLINE RESECTABLE PANCREATIC CANCER (PREOPANC) : <BR />A RANDOMIZED, CONTROLLED, MULTICENTER PHASE III TRIAL OF THE<BR /> DUTCH PANCREATIC CANCER GROUP
Presented By Geertjan Van Tienhoven at 2018 ASCO Annual Meeting
TRIAL DESIGN
Presented By Geertjan Van Tienhoven at 2018 ASCO Annual Meeting
DISEASE FREE SURVIVAL
Presented By Geertjan Van Tienhoven at 2018 ASCO Annual Meeting
OVERALL SURVIVAL (ITT)
Presented By Geertjan Van Tienhoven at 2018 ASCO Annual Meeting
NEOADJUVANT FOLFIRINOX
• Phase II studies have given as much as 8 weeks of neoadjuvant FOLFIRINOX– Apparent higher rates of R0 resection– Majority of patients can receive full dose or
full number of cycles of FOLFIRINOX– On studies when resection is unable to be
performed, it is usually due to progression, not due to toxicity of therapy
• Many used xrt as well prior to surgeryMurphy, et al JAMA Oncol epub ahead of print May 3, 2018Katz, et al Jama Surg 151:e161137, 2016Yoo et al Oncotarget 8:46337-47, 2017
CONCLUSIONS
• FOLFIRINOX is now our standard adjuvant therapy for healthy patients
• Post-op FOLFIRINOX is proven– But ~25% of resected patients never get to
adjuvant therapy– Post-op delays systemic therapy in a systemic
disease• Pre-op FOLFIRINOX is safe and effective
– While some patients progress to unresectable, those patients are unlikely to ever benefit from surgery