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

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


What is the optimal sequence of therapies for stage ii iii adenocarcinoma of the proximal stomach

GASTRIC meta- adenocarcinoma of the proximal stomach?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


What is the optimal sequence of therapies for stage ii iii adenocarcinoma of the proximal stomach

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


What is the optimal sequence of therapies for stage ii iii adenocarcinoma of the proximal stomach

Rationale for administered to all patients…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)


Perioperative or pre operative chemotherapy
Perioperative or pre-operative chemotherapy administered to all patients…

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.


Stage inclusion criteria
Stage – Inclusion criteria administered to all patients…

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.


Pathology results
Pathology Results administered to all patients…

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.


Overall survival
Overall Survival administered to all patients…

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.


Magic survival
MAGIC - Survival administered to all patients…

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


Meta analysis of pre peri operative treatment
Meta-analysis of pre/ administered to all patients…peri-operative treatment

Survival

Ge L et al. World J Gastroenterol 2012;18:7384-7393


Comparison between adjuvant and pre perioperative treatment
Comparison between adjuvant and pre/perioperative treatment administered to all patients…

Modified from Philippe Rougier


What is the optimal sequence of therapies for stage ii iii adenocarcinoma of the proximal stomach

Pre/perioperative treatment – administered to all patients…

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)


Magic b sto 03
MAGIC – B – STO-03 administered to all patients…

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


Critics

³ administered to all patients…

“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