What to expect from HER-2 directed therapies in advanced gastric cancer?

Abstract

Gastric cancer is the second most common cause of cancer
related death worldwide. Over 20% of the advanced gastric
cancer are considered to be HER-2 positive. Studies
investigating the prognosis of HER-2 positive advanced
gastric cancer revealed conflicting results. Trastuzumab, a
monoclonal antibody against HER-2, has shown a significant
clinical activity in HER-2 positive gastric cancer patients. In
this review, I will briefly summarize the clinical studies of
anti-HER-2 therapies performed in HER-2 positive gastric
carcinoma.
Keywords: Gastric cancer, HER-2/neu, Targeted therapy

Keywords

• Gastric cancer, HER-2/neu, Targeted therapy

References

1. 1. Garcia M, Jemal A, Ward EM, et al. Global cancer facts and figures 2007. Atlanta, GA: American Cancer Society, 2007.
2. 2. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across fi ve continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 2006; 24: 2137–50. doi: 10.1200/ JCO.2005.05.2308
3. 3. Cunningham D, Starling N, Rao S, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 2008; 358:36. doi: 10.1056/NEJMoa073149.
4. 4. Ajani JA, Moiseyenko VM, Tjulandin S, et al. Clinical benefit with docetaxel plus fluorouracil and cisplatin compared with cisplatin and fluorouracil in a phase III trial of advanced gastric or gastroesophageal cancer adenocarcinoma: the V-325 Study Group. J Clin Oncol 2007; 25:3205. doi: 10.1200/JCO.2006.10.4968
5. 5. Schechter AL, Hung MC, Vaidyanathan L, et al. The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science 1985; 229(4717):976-8.
6. 6. Yamamoto T, Ikawa S, Akiyama T, et al. Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature 1986;319(6050):230-4.
7. 7. Park YS, Hwang HS, Park HJ, et al. Comprehensive analysis of HER2 expression and gene amplification in gastric cancers using immunohistochemistry and in situ hybridization: which scoring system should we use? Hum Pathol 2012; 43:413. doi: 10.1016/j. humpath.2011.05.019.
8. 8. Barros-Silva JD, Leitão D, Afonso L, et al. Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients. Br J Cancer 2009; 100:487. doi: 10.1038/ sj.bjc.6604885.

9. 9. Baykara M, Benekli M, Ekinci O, Irkkan C,DemirciU, Karaca H, Unal O.U,Dane F, Akinci B, Turkoz F.P. Clinical significance of HER2 overexpression in gastric and gastro-esophageal junction cancers: Is there any discordance between IHC and FISH. ESMO 2012, abst:2778.
10. 10. Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 2008;52:797-805. doi:10.1111/j.1365-2559.2008.03028.x.
11. 11. Bang Y, Chung H, Xu J, et al. Pathological features of advanced gastric cancer (GC): Relationship to human epidermal growth factor receptor 2 (HER2) positivity in the global screening programme of the ToGA trial (abstract). J Clin Oncol 2009; 27:215s.
12. 12. Rüschoff J, Dietel M, Baretton G, et al. HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing. Virchows Arch 2010; 457:299. doi: 10.1007/ s00428-010-0952-2.
13. 13. Gordon MA, Gundacker HM, Benedetti J, et al. Assessment of HER2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial. Ann Oncol 2013; 24:1754. doi: 10.1093/annonc/mdt106.
14. 14. Terashima M, Kitada K, Ochiai A, et al. Impact of expression of human epidermal growth factor receptors EGFR and ERBB2 on survival in stage II/ III gastric cancer. Clin Cancer Res 2012; 18:5992.doi: 10.1158/1078-0432.CCR-12-1318.
15. 15. Lordick F, Kang YK, Chung HC, et al. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol 2013; 14:490. doi: 10.1016/S1470- 2045(13)70102-5.
16. 16. Waddell T, Chau I, Cunningham D, et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol 2013; 14:481. doi: 10.1016/S1470-2045(13)70096-2.
17. 17. Van Cutsem E, de Haas S, Kang YK, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. J Clin Oncol 2012; 30:2119.doi: 10.1200/JCO.2011.39.9824.
18. 18. Janjigian YY, Werner D, Pauligk C, et al. Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis. Ann Oncol 2012; 23:2656. doi: 10.1093/annonc/mds104
19. 19. Okines AF, Thompson LC, Cunningham D, et al. Effect of HER2 on prognosis and benefit from perioperative chemotherapy in early oesophago-gastric adenocarcinoma in the MAGIC trial. Ann Oncol 2013; 24:1253. doi: 10.1093/annonc/mds622.
20. 20. Chua TC, Merrett ND. Clinicopathologic factors associated with HER2-positive gastric cancer and its impact on survival outcomes--a systematic review. Int J Cancer 2012; 130:2845. doi: 10.1002/ijc.26292.
21. 21. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010; 376:687. doi: 10.1016/S0140- 6736(10)61121-X.
22. 22. Ryu MH, Yoo C, Kim JG, Ryoo BY, Park YS, Park SR, Han HS, Chung IJ, Song EK, Lee KH, Kang SY, Kang YK. Multicenter phase II study of trastuzumab in combination with capecitabine and oxaliplatin for advanced gastric cancer. Eur J Cancer 2015;5:482-8. doi:10.1016/j.ejca.2014.12.015.
23. 23. Hecht JR, Bang YJ, Qin S, et al. Lapatinib in combination with capecitabine plus oxaliplatin (CapeOx) in HER2- positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma (AC): The TRIO- 013/LOGiC Trial. J Clin Oncol 31, 2013 (suppl; abstr LBA4001)
24. 24. Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, Tsuji A, Omuro Y, Li J, Wang JW, Miwa H, Qin SK, Chung IJ, Yeh KH, Feng JF, Mukaiyama A, Kobayashi M, Ohtsu A, Bang YJ. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2- amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study. J Clin Oncol 2014;32:2039-49. doi: 10.1200/JCO.2013.53.6136.
25. 25. A Study of Perjeta (Pertuzumab) in Combination With Herceptin (Trastuzumab) and Chemotherapy in Patients With HER2-Positive Metastatic Gastroesophageal Junction or Gastric Cancer. Available from: https://clinicaltrials.gov/ct2/show/ NCT01774786?term=NCT01774786&rank=1
26. 26. A Study of Trastuzumab Emtansine versus Taxane in Patients with Advanced Gastric Cancer. Available from: https://clinicaltrials.gov/ct2/show/ NCT01641939?term=NCT01641939&rank=1
27. 27. A Study of the Combination of Oxaliplatin, Capecitabine and Herceptin (Trastuzumab) and Chemoradiotherapy in The Adjuvant Setting in Operated Patients With HER2+ Gastric or GastroEsophageal Junction Cancer (TOXAG Study). Available from: https://clinicaltrials.gov/ct2/show/ NCT01748773?term=NCT01748773&rank=1