NO Bassel F. El-Rayes 1 Basic Principles Clinical practice - PowerPoint PPT Presentation

Role of radiation in resectable and locally advanced pancreatic cancer? NO Bassel F. El-Rayes 1

Basic Principles • Clinical practice should be • Clinical practice should not be based on data showing benefit based on absence of data of an intervention showing futility • The only time we should add treatment modality B to A is when the data clearly confirms A+B is better than A alone Winship Cancer Institute | Emory University 2

Adjuvant Therapy 3

CONKO 001: Gemcitabine vs. Observation in Patients w ith Resected Pancreatic Cancer Oettle H, et al. JAMA . 2013;310(14):1473-1481. Winship Cancer Institute | Emory University 4

CONKO-001 Randomized Trial Median DFS 13.4 months (95% CI, 11.6-15.3 months) gemcitabine Median OS 22.8 months (95% CI, 18.5-27.2 months) 6.7 months (95% CI, 6.0-7.5 months) observation 20.2 months (95% CI, 17.7-22.8 months) hazard ratio, 0.55 [95% CI, 0.44-0.69] hazard ratio, 0.76 [95% CI, 0.61-0.95] Oettle H, et al. JAMA . 2013;310(14):1473-1481. Winship Cancer Institute | Emory University 5

Oettle H, et al. JAMA . 2013;310(14):1473-1481. Winship Cancer Institute | Emory University 6

ESPAC-1: A Randomized Trial of Chemoradiotherapy and Chemotherapy after Resection of Pancreatic Cancer The Two-by-Two Randomization Procedure Used for Both Chemoradiotherapy and Chemotherapy. Neoptolemos JP, et al. N Engl J Med. 2004;350(12):1200-1210. Winship Cancer Institute | Emory University 7

Overall Survival ESPAC-1 Trial Neoptolemos JP, et al. N Engl J Med. 2004;350(12):1200-1210.

ESPAC 4: Gemcitabine vs Gemcitabine Capecitabine in Resected Pancreatic Cancer Neoptolemos JP, et al. Lancet. 2017;389(10073):1011-1024. Winship Cancer Institute | Emory University 9

Survival by Treatment Neoptolemos JP, et al. Lancet. 2017;389(10073):1011-1024. Winship Cancer Institute | Emory University 10

Survival by treatment ESPAC-4 Neoptolemos JP, et al. Lancet. 2017;389(10073):1011-1024. Winship Cancer Institute | Emory University 11

EORTC 40891 ESPAC-1 GITSG 91-73 Study Kalser MH, et al. Arch Surg. 1986;121(9):1045. Smeenk HG, et al. Ann Surg. 2007;246(5):734-740. Neoptolemos JP, et al. N Engl J Med. 2004;350(12):1200-1210. Winship Cancer Institute | Emory University 12

Local Recurrence RTOG 9704 ESPAC-4 Regine WF, et al. JAMA. 2008;299(9):1019-1026. Neoptolemos JP, et al. Lancet. 2017;389(10073):1011-1024. Winship Cancer Institute | Emory University 13

Survival Adjuvant Trials Chemotherapy Chemoradiotherapy • CONKO-1 • ESPAC-1 • 22.8 months (Gem) • 15.9 months (5FU XRT) • ESPAC-1 • RTOG 9704 (HOP) • 20 months (5FU) • 20.5 months (Gem XRT) • 17.1 months (5FU XRT) • ESPAC-3 • 23 months (5FU) • 23.6 months (Gem) • ESPAC-4 • 25.5 moths (Gem) • 28.0 months (Gem Cap) Winship Cancer Institute | Emory University 14

RTOG 0848 5 cycles 1 cycle D R R I Gemcitabine A A Gemcitabine S R +/- Erlotinib N N E E A D D S S O O T E M A M G I I F Gemcitabine Gemcitabine E R Z Z FP/XRT Erlotinib +/- Erlotinib E E E E Winship Cancer Institute | Emory University 15

Locally advanced disease 16

FFCD-SFRO ECOG LAP-07 Median OS- 8.6 months Median OS- 11.1 months Median OS- 15.2 months Gem ChemoRT Chauffert B, et al. Ann Oncol. 2008;19(9):1592-1599. Loehrer P, et al. J Clin Oncol. 2011;29(31):4105-4112. Hammel P, et al. JAMA . 2016;315(17):1844-1853. Winship Cancer Institute | Emory University 17

FOLFIRINOX for Locally Advanced Pancreatic Cancer Suker M, et al. Lancet Oncol. 2016;17(6):801-810. Winship Cancer Institute | Emory University 18

FOLFIRINOX for locally advanced pancreatic cancer • Median OS 24.2 months • Median PFS 15.0 months Suker M, et al. Lancet Oncol. 2016;17(6):801-810. Winship Cancer Institute | Emory University 19

Winship Cancer Institute | Emory University 20

Basic Principles • Clinical practice should be • Clinical practice should not be based on data showing benefit based on absence of data of an intervention showing futility • The only time we should add treatment modality B to A is when the data clearly confirms A+B is better than A alone Winship Cancer Institute | Emory University 21

Conclusion • Chemotherapy is an established treatment in the adjuvant setting in pancreas cancer • Multiple randomized trials showing benefit with advantage for gemcitabine and capecitabine • NO well-designed and adequately powered randomized trial has shown benefit for adjuvant radiation therapy • Chemoradiotherapy in locally advanced disease results are mixed with NO clear advantage shown over chemotherapy • Intensification of chemotherapy appears to be a promising approach in this setting Winship Cancer Institute | Emory University 22