Current Management of Gastric Cancer.

1. Advanced Gastric Cancer:
Can We Go Better?
Mohamed Abdulla M.D.
Prof. of Clinical Oncology
Cairo University
Assiut 23/02/2016

2. Speaker Disclosures:
Member of Advisory Board, Consultant, and Speaker for:
• Amgen, Astellas, AstraZeneca, Hoffman la Roche, Janssen Cilag,
Merck Serono, Novartis, Pfizer
• The content of this presentation does not relate to any product of a
commercial interest

3. Objectives:
• Emphasizing the multi-modal approach in
gastric cancer management.
• The value of adding radiation therapy.
• Molecular classification of gastric cancer.
• Biologics can expand the landscape of
advanced stages of disease.

4. Basic Facts:
• Decreasing incidence over past decades.
• 3rd Leading Cause of Cancer Related Death (2012).
• 80% at presentation: advanced, metastatic or recurrent
 median survival < 1 year. 10 – Year OAS (all stages)
20%.
• Shift from distal to proximal lesions (GEJ) & among
whites.
• Surgical resection is the cornerstone in curative
management  loco-regional failures (40 – 65%).
• East versus West.
Landry et al. Patterns of failure following curative resection of gastric cancer. Int J Ra- diat Oncol Biol Phys 1990;191:1357-62.
Jemal etal. Cancer Statistics, 2010. CA Cancer J Clin 2010.
Ferlay et al, GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide. IARC CancerBase, accessed 16/12/14.
International Agency for Research on Cancer.

5. Recurrence After Surgery:
Wong et al. J Gastrointest Oncol 2015;6(1):89-107
Surgery Alone is Not Enough.

6. Principles of Management:
1. Chemotherapy versus BSC:
• HR (OAS) = 0.49.
• Survival Advantage = 4.3 to 11 months.
• Total Survival with maintained High Quality of Life (69% - 47% P < .05)
Wagner et al. J Clin Oncol 24:2903-2909. 2006

7. Principles of Management:
2. Combination versus Single Agent Chemotherapy:
Wagner et al. J Clin Oncol 24:2903-2909. 2006
Wagner et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev 2010; CD004064.
• Fluoropyremidines & Platinum.
• Fluoropyremidines
Monotherapy  Combination
is not Feasible.

8. Principles of Management:
3. Combination Chemotherapy:
5-Fu Cisplatin
Capecitabin
e
Oxaliplatin
+
Anthracyclines
Docetaxel/
Irinotecan
• Basic Benchmark Duplet.
• Substitutions = Variations on Same Melody.
• Triplets  REAL 2 Study.
5-Fu – Cisplatin =
Capecitabine – Cisplatin =
5-Fu – Oxaliplatin =
Capecitabine – Oxaliplatin
Wagner et al. Cochrane Database Syst Rev 2010; CD004064. Kang et al, Ann Oncol 2009; 20:666-73. Cunningham et al, N Engl J
Med 2008; 358:36-46. Okines et al, Ann Oncol 2009; 20:1529-34

9. 1002 AGC
Patients
263 = ECF
250 = ECX
245 = EOF
244 = EOX
Principles of Management:
3. Combination Chemotherapy: REAL 2 Study:
Non - Inferiority
HR =
.86
HR =
.92
HR =
.80
P = 0.02
Cunningham et al, N Engl J Med 2008; 358:36-46.

10. Principles of Management:
3. Combination Chemotherapy: First Line Trials:

11. Principles of Management:
3. Combination Chemotherapy: MAGIC Trial:
503
Resectable
Gastric
Cancer
Surgery =
253
ECF X 3 =
250
Surgery
ECF X 3 =
250
1ry Endpoint: OAS

12. Principles of Management:
3. Combination Chemotherapy: MAGIC Trial:
Cunningham et al, N Engl J Med. 2006;355:11-20

13. Principles of Management:
3. Combination Chemotherapy: INT 0116 Adjuvant:
556 Patients
(T1-4 N0-1)
Surgery
(D1 or Less)
Observation
CRT
S = 27 ms
S + CRT = 36 ms
P = 0.005
S = 19 ms
S + CRT = 30 ms
P < 0.001
Macdonald et al. N Engl J Med, Vol. 345, No. 10 · September 6, 2001

14. Updated Analysis of SOWG – Directed
Intergroup 01116 Trial
Smalley et al. J Clin Oncol. 2012 30:2327-2333.

15. 458 Patients
Non-Metastatic
Gastric Cancer
D2 Resection
XP X 6
XP/XRT/XP
Lee at al. J Clin Oncol. 2012 30:268-273
Principles of Management:
3. Combination Chemotherapy: ARTIST Trial:

16. ARTIST Trial: 7 – Year Updated
Analysis:
Park et al. J Clin Oncol. 2015.33:3130-3136
XP XRT P
LR 13% 7% 0.0033
DFS (LNs +) 72% 76% 0.004
Postoperative Radiation Therapy:
• Positive LNs.
• Intestinal (Non Diffuse) histopathology.

17. Who Benefits of Adjuvant Radiation
Therapy?

18. Who Benefits of Adjuvant Radiation
Therapy?
OAS DFS
Ohri et al. Int J Radiation Oncol Biol Phys, Vol. 86, No. 2, pp. 330e335, 2013

19. Who Benefits of Adjuvant Radiation
Therapy?
Ohri et al. Int J Radiation Oncol Biol Phys, Vol. 86, No. 2, pp. 330e335, 2013
OAS By
Nodal Dissection
 20% in OAS & DFS

20. Who Benefits of Adjuvant Radiation
Therapy?
Ohri et al. Int J Radiation Oncol Biol Phys, Vol. 86, No. 2, pp. 330e335, 2013
Radiation Therapy
Incomplete Nodal
Dissection
Intestinal Type
Positive Nodal Disease

21. Multi-Modal Treatment of GC:
Schirren et al. Ther Adv Med Oncol.2015, Vol. 7(1) 39–48
Multimodal Treatment is Superior to Single Modality (Surgery).

22. Pathogenesis of Gastric Cancer:
Tan & Yeoh. Gastroenterology 2015;149:1153–1162

23. Molecular Subtypes of GC and Key Features

24. Gastric Cancer: Molecular Subtypes, Genetic
Alterations & Treatment Sensitivity:
Lei et al. Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-
fluorouracil. Gastroenterology 2013;145:554–65.

25. Role of Targeted Agents:
• HER 2 Overexpression:
– 15 – 20% of cases.
– More in proximal lesions.
– Never in diffuse type.
– Different scoring system than in breast cancer.
• Angiogenesis:
– Formation of abnormal new vasculature (Key
process in tumorogenesis.
– Responsible for Oxygen and Nutrients delivery to a
growing tumor.

26. Role of Targeted Agents:
F. Lordick et al. / Cancer Treatment Reviews 40 (2014) 692–700

27. Take Home Message:
• Heterogenous disease entity.
• Multimodal approach is highly appreciated.
• Radiation therapy in selected patients 
decreasing locoregional failures.
• Duplets and triples are the backbone of any
agent.
• Clinical trials are awaited.