Challenges in molecular targeted therapy for gastric cancer: considerations for efficacy and safety

References

• Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–386.
   PubMed Web of Science ®Google Scholar
• Glimelius B, Ekstrom K, Hoffman K, et al. Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol. 1997;8:163–168.
   PubMed Web of Science ®Google Scholar
• Murad AM, Santiago FF, Petroianu A, et al. Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer. 1993;72:37–41.
   PubMed Web of Science ®Google Scholar
• Pyrhonen S, Kuitunen T, Nyandoto P, et al. Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer. 1995;71:587–591.
   PubMed Web of Science ®Google Scholar
• 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;25:3205–3209.
   PubMed Web of Science ®Google Scholar
• Cunningham D, Starling N, Rao S, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358:36–46.
   PubMed Web of Science ®Google Scholar
• Koizumi W, Narahara H, Hara T, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008;9:215–221.
   PubMed Web of Science ®Google Scholar
• Riquelme I, Saavedra K, Espinoza JA, et al. Molecular classification of gastric cancer: towards a pathway-driven targeted therapy. Oncotarget. 2015;6:24750–24779.
   PubMed Web of Science ®Google Scholar
• Cancer Genome Atlas Research N. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513:202–209.
   PubMed Web of Science ®Google Scholar
• Franklin WA, Veve R, Hirsch FR, et al. Epidermal growth factor receptor family in lung cancer and premalignancy. Semin Oncol. 2002;29:3–14.
   PubMed Web of Science ®Google Scholar
• Jones KL, Buzdar AU. Evolving novel anti-HER2 strategies. Lancet Oncol. 2009;10:1179–1187.
   PubMed Web of Science ®Google Scholar
• Lurje G, Lenz HJ. EGFR signaling and drug discovery. Oncology. 2009;77:400–410.
   PubMed Web of Science ®Google Scholar
• Jorgensen JT, Hersom M. HER2 as a prognostic marker in gastric cancer – a systematic analysis of data from the literature. J Cancer. 2012;3:137–144.
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Bang YJ, Feng-Yi F, et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015;18:476–484.
   PubMed Web of Science ®Google Scholar
• 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;376:687–697.
   PubMed Web of Science ®Google Scholar
• Seidman A, Hudis C, Pierri MK, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 2002;20:1215–1221.
   PubMed Web of Science ®Google Scholar
• Emens LA. Trastuzumab: targeted therapy for the management of HER-2/neu-overexpressing metastatic breast cancer. Am J Ther. 2005;12:243–253.
   PubMedGoogle Scholar
• Hecht JR, Bang YJ, Qin SK, et al. Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: TRIO-013/LOGiC – a randomized phase III trial. J Clin Oncol. 2016;34:443–451.
   PubMed Web of Science ®Google Scholar
• 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;14:490–499.
   PubMed Web of Science ®Google Scholar
• Okines AF, Ashley SE, Cunningham D, et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for advanced esophagogastric cancer: dose-finding study for the prospective multicenter, randomized, phase II/III REAL-3 trial. J Clin Oncol. 2010;28:3945–3950.
   PubMed Web of Science ®Google Scholar
• Cunningham D, Tebbutt NC, Davidenko I. Phase III, randomized, double-blind, multicenter, placebo (P)-controlled trial of rilotumumab (R) plus epirubicin, cisplatin and capecitabine (ECX) as first-line therapy in patients (pts) with advanced MET-positive (pos) gastric or gastroesophageal junction (G/GEJ) cancer: RILOMET-1 study. J Clin Oncol. 2015; 33: (suppl; abstr 4000)
   Google Scholar
• Shah MA, Bang Y-J, Lordick F, et al. METGastric: a randomized phase III study of onartuzumab (MetMAb) in combination with mFOLFOX6 in patients with metastatic HER2-negative and MET-positive adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol. 2015;33(suppl; abstr 4012).
   Google Scholar
• Ohtsu A, Shah MA, Van Cutsem E, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011;29:3968–3976.
   PubMed Web of Science ®Google Scholar
• Satoh T, Xu RH, Chung HC, et al. 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;32:2039–2049.
   PubMed Web of Science ®Google Scholar
• Kang Y-K, Shah MA, Ohtsu A, et al. A randomized, open-label, multicenter, adaptive phase 2/3 study of trastuzumab emtansine (T-DM1) versus a taxane (TAX) in patients (pts) with previously treated HER2-positive locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (LA/MGC/GEJC). J Clin Oncol. 2016;34(suppl 4S; abstr 5).
   Google Scholar
• Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383:31–39.
   PubMed Web of Science ®Google Scholar
• Wilke H, Muro K, Van Cutsem E, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15:1224–1235.
   PubMed Web of Science ®Google Scholar
• Bang Y, Boku N, Chin K et al. Olaparib in combination with paclitaxel with advanced gastric cancer who have progressed following first-line therapy: phase III GOLD study. ESMO congress 2016; LBA25.
   Google Scholar
• Ohtsu A, Ajani JA, Bai YX, et al. Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study. J Clin Oncol. 2013;31:3935–3943.
   PubMed Web of Science ®Google Scholar
• Li J, Qin S, Xu J, et al. Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol. 2016;34:1448–1454.
   PubMed Web of Science ®Google Scholar
• Guan Z, Xu B, DeSilvio ML, et al. Randomized trial of lapatinib versus placebo added to paclitaxel in the treatment of human epidermal growth factor receptor 2-overexpressing metastatic breast cancer. J Clin Oncol. 2013;31:1947–1953.
   PubMed Web of Science ®Google Scholar
• Kang Y-K, Ma S, Ohtsu A, et al. High procedure volume is strongly associated with improved survival after lung cancer surgery. J Clin Oncol. 2013;31(25):3141–3146.
   PubMed Web of Science ®Google Scholar
• Kwak EL, Ahronian LG, Siravegna G, et al. Molecular heterogeneity and receptor coamplification drive resistance to targeted therapy in met-amplified esophagogastric cancer. Cancer Discov. 2015;5:1271–1281.
   PubMed Web of Science ®Google Scholar
• Kuboki Y, Yamashita S, Niwa T, et al. Comprehensive analyses using next-generation sequencing and immunohistochemistry enable precise treatment in advanced gastric cancer. Ann Oncol. 2016;27:127–133.
   PubMed Web of Science ®Google Scholar
• Mitsui F, Dobashi Y, Imoto I, et al. Non-incidental coamplification of myc and ERBB2, and myc and EGFR, in gastric adenocarcinomas. Mod Pathol. 2007;20:622–631.
   PubMed Web of Science ®Google Scholar
• Satoh T, Lee KH, Rha SY, et al. Randomized phase II trial of nimotuzumab plus irinotecan versus irinotecan alone as second-line therapy for patients with advanced gastric cancer. Gastric Cancer. 2014;18:824–832.
   Web of Science ®Google Scholar
• 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;14:481–489.
   PubMed Web of Science ®Google Scholar
• Ruschoff J, Hanna W, Bilous M, et al. HER2 testing in gastric cancer: a practical approach. Mod Pathol. 2012;25:637–650.
   PubMed Web of Science ®Google Scholar
• Ruschoff J, Dietel M, Baretton G, et al. HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing. Virchows Arch. 2010;457:299–307.
   PubMed Web of Science ®Google Scholar
• Lee HE, Park KU, Yoo SB, et al. Clinical significance of intratumoral HER2 heterogeneity in gastric cancer. Eur J Cancer. 2013;49:1448–1457.
   PubMed Web of Science ®Google Scholar
• Janjigian YY, Riches JC, Ku GY, et al. Loss of human epidermal growth factor receptor 2 (HER2) expression in HER2-overexpressing esophagogastric (EG) tumors treated with trastuzumab. J Clin Oncol. 2015;33(suppl 3; abstr 63).
   PubMed Web of Science ®Google Scholar
• Kowanetz M, Ferrara N. Vascular endothelial growth factor signaling pathways: therapeutic perspective. Clin Cancer Res. 2006;12:5018–5022.
   PubMed Web of Science ®Google Scholar
• Cao W, Fan R, Yang W, et al. VEGF-C expression is associated with the poor survival in gastric cancer tissue. Tumour Biol. 2014;35:3377–3383.
   PubMed Web of Science ®Google Scholar
• Yoshikawa T, Tsuburaya A, Kobayashi O, et al. Plasma concentrations of VEGF and bFGF in patients with gastric carcinoma. Cancer Lett. 2000;153:7–12.
   PubMed Web of Science ®Google Scholar
• Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–676.
   PubMed Web of Science ®Google Scholar
• Jung YD, Mansfield PF, Akagi M, et al. Effects of combination anti-vascular endothelial growth factor receptor and anti-epidermal growth factor receptor therapies on the growth of gastric cancer in a nude mouse model. Eur J Cancer. 2002;38:1133–1140.
   PubMed Web of Science ®Google Scholar
• Tanigawa N, Amaya H, Matsumura M, et al. Correlation between expression of vascular endothelial growth factor and tumor vascularity, and patient outcome in human gastric carcinoma. J Clin Oncol. 1997;15:826–832.
   PubMed Web of Science ®Google Scholar
• Sun W, Powell M, O’Dwyer PJ, et al. Phase II study of sorafenib in combination with docetaxel and cisplatin in the treatment of metastatic or advanced gastric and gastroesophageal junction adenocarcinoma: ECOG 5203. J Clin Oncol. 2010;28:2947–2951.
   PubMed Web of Science ®Google Scholar
• Martin-Richard M, Gallego R, Pericay C, et al. Multicenter phase II study of oxaliplatin and sorafenib in advanced gastric adenocarcinoma after failure of cisplatin and fluoropyrimidine treatment. A GEMCAD Study. Invest New Drugs. 2013;31:1573–1579.
   PubMed Web of Science ®Google Scholar
• Moehler M, Mueller A, Hartmann JT, et al. An open-label, multicentre biomarker-oriented AIO phase II trial of sunitinib for patients with chemo-refractory advanced gastric cancer. Eur J Cancer. 2011;47:1511–1520.
   PubMed Web of Science ®Google Scholar
• Bang YJ, Kang YK, Kang WK, et al. Phase II study of sunitinib as second-line treatment for advanced gastric cancer. Invest New Drugs. 2011;29:1449–1458.
   PubMed Web of Science ®Google Scholar
• Shen L, Li J, Xu J, et al. Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer: randomized, double-blind, phase III study (AVATAR study). Gastric Cancer. 2015;18:168–176.
   PubMed Web of Science ®Google Scholar
• Spratlin JL, Cohen RB, Eadens M, et al. Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol. 2010;28:780–787.
   PubMed Web of Science ®Google Scholar
• Shitara K, Muro K, Shimada Y, et al. Subgroup analyses of the safety and efficacy of ramucirumab in Japanese and Western patients in RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer. Gastric Cancer. 2016;19:927–938.
   PubMed Web of Science ®Google Scholar
• Yoon HH, Bendell JC, Braiteh FS, et al. Ramucirumab (RAM) plus FOLFOX as front-line therapy (Rx) for advanced gastric or esophageal adenocarcinoma (GE-AC): randomized, double-blind, multicenter phase 2 trial. J Clin Oncol. 2014;32(suppl; abstr 4004):5s.
   PubMed Web of Science ®Google Scholar
• Moore M, Gill S, Asmis T, et al. Randomized phase II study of modified FOLFOX-6 in combination with ramucirumab or icrucumab as second-line therapy in patients with metastatic colorectal cancer after disease progression on first-line irinotecan-based therapy. Ann Oncol. 2016. [Epub ahead of print].
   Google Scholar
• Shitara K, Sawaki A, Matsuo K, et al. A retrospective comparison of S-1 plus cisplatin and capecitabine plus cisplatin for patients with advanced or recurrent gastric cancer. Int J Clin Oncol. 2012;8:539–546.
   PubMed Web of Science ®Google Scholar
• Shitara K, Yuki S, Tahahari D, et al. Randomised phase II study comparing dose-escalated weekly paclitaxel vs standard-dose weekly paclitaxel for patients with previously treated advanced gastric cancer. Br J Cancer. 2014;110:271–277.
   PubMed Web of Science ®Google Scholar
• Kadowaki S, Komori A, Takahari D, et al. Clinical characteristics associated with long-term survival in metastatic gastric cancer after systemic chemotherapy. Asian Pac J Cancer Prev. 2015;16:5433–5438.
   PubMedGoogle Scholar
• Roohullah A, Wong HL, Sjoquist KM, et al. Gastrointestinal perforation in metastatic colorectal cancer patients with peritoneal metastases receiving bevacizumab. World J Gastroenterol. 2015;21:5352–5358.
   PubMed Web of Science ®Google Scholar
• Imbulgoda A, MacLean A, Heine J, et al. Colonic perforation with intraluminal stents and bevacizumab in advanced colorectal cancer: retrospective case series and literature review. Can J Surg. 2015;58:167–171.
   PubMed Web of Science ®Google Scholar
• Enzinger PC, McCleary NJ, Zheng H, et al. Multicenter double-blind randomized phase II: FOLFOX + ziv-aflibercept/placebo for patients (pts) with chemo-naive metastatic esophagogastric adenocarcinoma (MEGA). J Clin Oncol. 2016;34(suppl 4S; abstr 4).
   PubMed Web of Science ®Google Scholar
• Pavlakis N, Sjoquist KM, Martin AJ, et al. Regorafenib for the treatment of advanced gastric cancer (integrate): a multinational placebo-controlled phase II trial. J Clin Oncol. 2016;34:2728–2735.
   PubMed Web of Science ®Google Scholar
• Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381:303–312.
   PubMed Web of Science ®Google Scholar
• Gherardi E, Birchmeier W, Birchmeier C, et al. Targeting MET in cancer: rationale and progress. Nat Rev Cancer. 2012;12:89–103.
   PubMed Web of Science ®Google Scholar
• Watanabe M, Ebina M, Orson FM, et al. Hepatocyte growth factor gene transfer to alveolar septa for effective suppression of lung fibrosis. Mol Ther. 2005;12:58–67.
   PubMed Web of Science ®Google Scholar
• Sunakawa Y, Wakatsuki T, Yang D, et al. Prognostic impact of the c-MET polymorphism on the clinical outcome in locoregional gastric cancer patients. Pharmacogenet Genomics. 2014;24:588–596.
   PubMed Web of Science ®Google Scholar
• Wang JY, Hsieh JS, Chen CC, et al. Alterations of APC, c-met, and p53 genes in tumor tissue and serum of patients with gastric cancers. J Surg Res. 2004;120:242–248.
   PubMed Web of Science ®Google Scholar
• Shah MA, Cho JY, Tan IB, et al. A randomized phase II study of FOLFOX with or without the MET inhibitor onartuzumab in advanced adenocarcinoma of the stomach and gastroesophageal junction. Oncologist. 2016;21:1085–1090.
   PubMed Web of Science ®Google Scholar
• Doshi S, Gisleskog PO, Zhang Y, et al. Rilotumumab exposure-response relationship in patients with advanced or metastatic gastric cancer. Clin Cancer Res. 2015;21:2453–2461.
   PubMed Web of Science ®Google Scholar
• Iveson T, Donehower RC, Davidenko I, et al. Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study. Lancet Oncol. 2014;15:1007–1018.
   PubMed Web of Science ®Google Scholar
• Feldman ME, Apsel B, Uotila A, et al. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. Plos Biol. 2009;7:e38.
   PubMed Web of Science ®Google Scholar
• Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917–921.
   PubMed Web of Science ®Google Scholar
• Bang YJ, Im SA, Lee KW, et al. Randomized, double-blind phase II trial with prospective classification by ATM protein level to evaluate the efficacy and tolerability of olaparib plus paclitaxel in patients with recurrent or metastatic gastric cancer. J Clin Oncol. 2015;33:3858–3865.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Jin Z, Zhou H, et al. Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin. Cancer Med. 2016;5:1251–1258.
   PubMed Web of Science ®Google Scholar
• Li Y, Rogoff HA, Keates S, et al. Suppression of cancer relapse and metastasis by inhibiting cancer stemness. Proc Natl Acad Sci U S A. 2015;112:1839–1844.
   PubMed Web of Science ®Google Scholar
• Becerra C, Stephenson J, Jonker DJ, et al. Phase Ib/II study of cancer stem cell (CSC) inhibitor BBI608 combined with paclitaxel in advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. J Clin Oncol. 2015;33(suppl; abstr 4069).
   Google Scholar
• Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364:2517–2526.
   PubMed Web of Science ®Google Scholar
• Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–2454.
   PubMed Web of Science ®Google Scholar
• Ferris RL, Blumenschein G Jr., Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375:1856–1867.
   PubMed Web of Science ®Google Scholar
• Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1803–1813.
   PubMed Web of Science ®Google Scholar
• Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375:1823–1833.
   PubMed Web of Science ®Google Scholar
• Muro K, Chung HC, Shankaran V, et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol. 2016;17:717–726.
   PubMed Web of Science ®Google Scholar
• Moehler MH, Cho JY, Kim YH, et al. A randomized, open-label, two-arm phase II trial comparing the efficacy of sequential ipilimumab (ipi) versus best supportive care (BSC) following first-line (1L) chemotherapy in patients with unresectable, locally advanced/metastatic (A/M) gastric or gastro-esophageal junction (G/GEJ) cancer. J Clin Oncol. 2016;34(suppl; abstr 4011).
   Google Scholar
• Janjigian YY, Bendell JC, Calvo E, et al. CheckMate-032: phase I/II, open-label study of safety and activity of nivolumab (nivo) alone or with ipilimumab (ipi) in advanced and metastatic (A/M) gastric cancer (GC). J Clin Oncol. 2016;34(suppl; abstr 4010).
   PubMed Web of Science ®Google Scholar
• Hyun CC, Hendrik-Tobias A, Lucjan W, et al. Avelumab (MSB0010718C; anti-PD-L1) in patients with advanced gastric or gastroesophageal junction cancer from JAVELIN solid tumor phase Ib trial: analysis of safety and clinical activity. J Clin Oncol. 2016;34(suppl; abstr 4009).
   Google Scholar