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What is the optimal sequence of therapies for stage II-III adenocarcinoma of the proximal stomach?

What is the optimal sequence of therapies for stage II-III adenocarcinoma of the proximal stomach? Peri -operative chemotherapy . Josep Tabernero, MD PhD Medical Oncology Department Vall d’Hebron University Hospital & Vall d’Hebron Institute of Oncology Barcelona.

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What is the optimal sequence of therapies for stage II-III adenocarcinoma of the proximal stomach?

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  1. What is the optimal sequence of therapies for stage II-III adenocarcinoma of the proximal stomach? Peri-operative chemotherapy  Josep Tabernero, MD PhD Medical Oncology Department Valld’Hebron University Hospital & Valld’Hebron Institute of Oncology Barcelona Great Debates & Updates in GI Malignancies NY, March 29th, 2014

  2. GASTRIC meta-analysis on individual data: Survival OS, CT + surgery OS, surgery alone DFS, CT + surgery DFS, surgery alone Survival proportion 77% of the recurrences occurred during the first 3 years OS HR = 0.81 95% CI = 0.74-0.87 p = 0.03 Follow-up (years) Gastric cancer meta-analysis. JAMA 2010;303:1729-37

  3. But adjuvant chemotherapy (radiotherapy) cannot be administered to all patients… 50 - 70% may receive adjuvant treatment but tolerance is poor: - Treatment delays - Dose reductions - Early termination Surgery “in the Real life” BUT: - Delayed surgical recovery - Poor food intake - Dumping syndrome - Poor performance status - Treatment refusal ~30 - 50%? Interest of pre/peri-operative treatment in resectable but infiltrating tumor

  4. Rationale for peri-operative or pre-operative chemotherapy • To offer chemotherapy treatment to a larger number of patients • To downsize/downstage the tumor • To facilitate the surgery • To decrease the risk of local recurrence and distant metastasis • To increase the overall survival • To offer a better safety profile and treatment tolerability • To offer a more effective treatment (compliance)

  5. Perioperative or pre-operative chemotherapy Preoperative chemotherapy Postoperative chemotherapy Surgery R Surgery Cunningham D et al. N Engl J Med 2006;355:11-20; Ychou Met al. J Clin Oncol 2011;29:1715-1721; Schuhmacher C et al. J Clin Oncol 2010;28:5210-5218.

  6. Stage – Inclusion criteria Cunningham D et al. N Engl J Med 2006;355:11-20; Ychou Met al. J Clin Oncol 2011;29:1715-1721; Schuhmacher C et al. J Clin Oncol 2010;28:5210-5218.

  7. Pathology Results Cunningham D et al. N Engl J Med 2006;355:11-20; Ychou Met al. J Clin Oncol 2011;29:1715-1721; Schuhmacher C et al. J Clin Oncol 2010;28:5210-5218.

  8. Overall Survival Cunningham D et al. N Engl J Med 2006;355:11-20; Ychou Met al. J Clin Oncol 2011;29:1715-1721; Schuhmacher C et al. J Clin Oncol 2010;28:5210-5218.

  9. MAGIC - Survival Cunningham D et al. N Engl J Med 2006;355:11-20

  10. Meta-analysis of pre/peri-operative treatment Survival Ge L et al. World J Gastroenterol 2012;18:7384-7393

  11. Comparison between adjuvant and pre/perioperative treatment Modified from Philippe Rougier

  12. Pre/perioperative treatment – Take home messages • Feasible and safe • Compliance: 90% preoperative, 50-70% post-operative • Significantly downstage/downsize the tumor and increase R0 resections • Does not increase perioperative morbidity and mortality • Significantly improves OS (13% at 5-yr in the largest studies)

  13. MAGIC – B – STO-03 Randomised ECX Repeated every 21 days for 3cycles ECX + Bevacizumab Repeated every 21 days for 3cycles Surgery 5 wk break from last pre-op chemo (8 wk break from last bevacizumab) 6-10 wk break before post-op chemo ECX Repeated every 21 days for 3cycles ECX + Bevacizumab Repeated every 21 days for 3cycles Maintenance Bevacizumab Every 21 days for 6 doses

  14. ³ “MAGIC”(3xECC) 15 Lymph nodes 45 Gy/25 fx + no splenectomy capecitabine dd Epirubicine / Cisplatin /Capecitabine cisplatin 1 - 5x pw 3D - CRT/IMRT CRITICS Preoperative chemotherapy 3x ECC q 3wks D1 + surgery 3x ECC q 3wks QoL R Preoperative chemotherapy 3x ECC q 3wks D1 + surgery Chemoradiation Tissue banking • Stratified for: • Centre • Histological type • Localisation of tumour

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