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Erschienen in: Current Treatment Options in Oncology 9/2020

01.09.2020 | Upper Gastrointestinal Cancers (JD Berlin, Section Editor)

Targeted Therapies in Advanced Gastric Cancer

verfasst von: Timil H. Patel, MD, Michael Cecchini, MD

Erschienen in: Current Treatment Options in Oncology | Ausgabe 9/2020

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Opinion statement

Despite a decreasing incidence in the USA, gastric cancer is highly prevalent worldwide. Furthermore, gastric cancer remains highly lethal with median survival of less than 1 year for metastatic disease. The backbone of therapy against metastatic gastric cancer remains cytotoxic chemotherapy, but recent advances in the molecular understanding of gastric cancer have renewed hope within that targeted agents can be leveraged to improve survival and reduce toxicity. For example, in patients with human epidermal growth factor-2 (HER2)-positive gastric cancer, the addition of trastuzumab to frontline chemotherapy improves survival. In the second line, oncologists can now administer a vascular endothelial growth factor (VEGF) receptor inhibitor, ramucirumab, as a single agent or in combination with chemotherapy, and the immune checkpoint inhibitor pembrolizumab is approved in multiple settings dependent on the Programmed Death Ligand 1 (PD-L1) status. For patients with metastatic disease, our approach to standard of care in the first-line setting is a 5FU/platinum doublet with trastuzumab for HER2-positive tumors. In the second-line setting, most patients receive ramucirumab + paclitaxel, but those that are MSI high receive pembrolizumab. For squamous cell carcinoma of the esophagus with high PD-L1 status (combined positive score (CPS) ≥ 10), we recommend pembrolizumab in the second line. While for PD-L1 ≥ 1% gastroesophageal adenocarcinoma, we do not recommend pembrolizumab before the third-line setting, although this may change in the near future for CPS ≥ 10. The future landscape for targeted therapy in gastric cancer is promising. Numerous clinical trials evaluating the combination immune therapy with molecularly targeted agents are generating much excitement. Moreover, genomic data from The Cancer Center Genome (TCGA) and Asian Cancer Research Group (ACRG) classifications is being used to identify molecular subtypes to enable future clinical trials to include biomarker-enriched patient populations.
Literatur
1.
Zurück zum Zitat Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMed Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMed
2.
Zurück zum Zitat Rahman R, Asombang AW, Ibdah JA. Characteristics of gastric cancer in Asia. World J Gastroenterol. 2014;20(16):4483–90.PubMedPubMedCentral Rahman R, Asombang AW, Ibdah JA. Characteristics of gastric cancer in Asia. World J Gastroenterol. 2014;20(16):4483–90.PubMedPubMedCentral
3.
Zurück zum Zitat Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965;64:31–49.PubMed Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965;64:31–49.PubMed
4.
Zurück zum Zitat Group G, Oba K, Paoletti X, Bang YJ, Bleiberg H, Burzykowski T, et al. Role of chemotherapy for advanced/recurrent gastric cancer: an individual-patient-data meta-analysis. Eur J Cancer. 2013;49(7):1565–77. Group G, Oba K, Paoletti X, Bang YJ, Bleiberg H, Burzykowski T, et al. Role of chemotherapy for advanced/recurrent gastric cancer: an individual-patient-data meta-analysis. Eur J Cancer. 2013;49(7):1565–77.
5.
Zurück zum Zitat Cancer Genome Atlas Research N. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202–9. Cancer Genome Atlas Research N. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202–9.
6.
Zurück zum Zitat Cristescu R, Lee J, Nebozhyn M, Kim KM, Ting JC, Wong SS, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015;21(5):449–56.PubMed Cristescu R, Lee J, Nebozhyn M, Kim KM, Ting JC, Wong SS, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015;21(5):449–56.PubMed
7.
Zurück zum Zitat Chivu-Economescu M, Matei L, Necula LG, Dragu DL, Bleotu C, Diaconu CC. New therapeutic options opened by the molecular classification of gastric cancer. World J Gastroenterol. 2018;24(18):1942–61.PubMedPubMedCentral Chivu-Economescu M, Matei L, Necula LG, Dragu DL, Bleotu C, Diaconu CC. New therapeutic options opened by the molecular classification of gastric cancer. World J Gastroenterol. 2018;24(18):1942–61.PubMedPubMedCentral
8.
Zurück zum Zitat Menard S, Pupa SM, Campiglio M, Tagliabue E. Biologic and therapeutic role of HER2 in cancer. Oncogene. 2003;22(42):6570–8.PubMed Menard S, Pupa SM, Campiglio M, Tagliabue E. Biologic and therapeutic role of HER2 in cancer. Oncogene. 2003;22(42):6570–8.PubMed
9.
Zurück zum Zitat Gassmann M, Casagranda F, Orioli D, Simon H, Lai C, Klein R, et al. Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor. Nature. 1995;378(6555):390–4.PubMed Gassmann M, Casagranda F, Orioli D, Simon H, Lai C, Klein R, et al. Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor. Nature. 1995;378(6555):390–4.PubMed
10.
Zurück zum Zitat Akiyama T, Sudo C, Ogawara H, Toyoshima K, Yamamoto T. The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science. 1986;232(4758):1644–6.PubMed Akiyama T, Sudo C, Ogawara H, Toyoshima K, Yamamoto T. The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science. 1986;232(4758):1644–6.PubMed
11.
Zurück zum Zitat Grillo F, Fassan M, Sarocchi F, Fiocca R, Mastracci L. HER2 heterogeneity in gastric/gastroesophageal cancers: from benchside to practice. World J Gastroenterol. 2016;22(26):5879–87.PubMedPubMedCentral Grillo F, Fassan M, Sarocchi F, Fiocca R, Mastracci L. HER2 heterogeneity in gastric/gastroesophageal cancers: from benchside to practice. World J Gastroenterol. 2016;22(26):5879–87.PubMedPubMedCentral
12.
Zurück zum Zitat Abrahao-Machado LF, Scapulatempo-Neto C. HER2 testing in gastric cancer: an update. World J Gastroenterol. 2016;22(19):4619–25.PubMedPubMedCentral Abrahao-Machado LF, Scapulatempo-Neto C. HER2 testing in gastric cancer: an update. World J Gastroenterol. 2016;22(19):4619–25.PubMedPubMedCentral
13.
Zurück zum Zitat Ruschoff J, Hanna W, Bilous M, Hofmann M, Osamura RY, Penault-Llorca F, et al. HER2 testing in gastric cancer: a practical approach. Mod Pathol. 2012;25(5):637–50.PubMed Ruschoff J, Hanna W, Bilous M, Hofmann M, Osamura RY, Penault-Llorca F, et al. HER2 testing in gastric cancer: a practical approach. Mod Pathol. 2012;25(5):637–50.PubMed
14.
Zurück zum Zitat Bartley AN, Washington MK, Colasacco C, Ventura CB, Ismaila N, Benson AB 3rd, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol. 2017;35(4):446–64.PubMed Bartley AN, Washington MK, Colasacco C, Ventura CB, Ismaila N, Benson AB 3rd, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol. 2017;35(4):446–64.PubMed
15.
Zurück zum Zitat Fujimoto-Ouchi K, Sekiguchi F, Yasuno H, Moriya Y, Mori K, Tanaka Y. Antitumor activity of trastuzumab in combination with chemotherapy in human gastric cancer xenograft models. Cancer Chemother Pharmacol. 2007;59(6):795–805.PubMed Fujimoto-Ouchi K, Sekiguchi F, Yasuno H, Moriya Y, Mori K, Tanaka Y. Antitumor activity of trastuzumab in combination with chemotherapy in human gastric cancer xenograft models. Cancer Chemother Pharmacol. 2007;59(6):795–805.PubMed
16.
Zurück zum Zitat • Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki 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(9742):687–97 This study resulted in the FDA approval of the first HER2 directed therapy in gastric cancer.PubMed • Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki 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(9742):687–97 This study resulted in the FDA approval of the first HER2 directed therapy in gastric cancer.PubMed
17.
Zurück zum Zitat Lewis Phillips GD, Li G, Dugger DL, Crocker LM, Parsons KL, Mai E, et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 2008;68(22):9280–90.PubMed Lewis Phillips GD, Li G, Dugger DL, Crocker LM, Parsons KL, Mai E, et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 2008;68(22):9280–90.PubMed
18.
Zurück zum Zitat Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, et al. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017;18(5):640–53.PubMed Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, et al. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017;18(5):640–53.PubMed
19.
Zurück zum Zitat Baselga J, Swain SM. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer. 2009;9(7):463–75.PubMed Baselga J, Swain SM. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer. 2009;9(7):463–75.PubMed
20.
Zurück zum Zitat Scheuer W, Friess T, Burtscher H, Bossenmaier B, Endl J, Hasmann M. Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res. 2009;69(24):9330–6.PubMed Scheuer W, Friess T, Burtscher H, Bossenmaier B, Endl J, Hasmann M. Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res. 2009;69(24):9330–6.PubMed
21.
Zurück zum Zitat Kang YK, Rha SY, Tassone P, Barriuso J, Yu R, Szado T, et al. A phase IIa dose-finding and safety study of first-line pertuzumab in combination with trastuzumab, capecitabine and cisplatin in patients with HER2-positive advanced gastric cancer. Br J Cancer. 2014;111(4):660–6.PubMedPubMedCentral Kang YK, Rha SY, Tassone P, Barriuso J, Yu R, Szado T, et al. A phase IIa dose-finding and safety study of first-line pertuzumab in combination with trastuzumab, capecitabine and cisplatin in patients with HER2-positive advanced gastric cancer. Br J Cancer. 2014;111(4):660–6.PubMedPubMedCentral
22.
Zurück zum Zitat Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, et al. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018;19(10):1372–84.PubMed Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, et al. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018;19(10):1372–84.PubMed
23.
Zurück zum Zitat Konecny GE, Pegram MD, Venkatesan N, Finn R, Yang G, Rahmeh M, et al. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res. 2006;66(3):1630–9.PubMed Konecny GE, Pegram MD, Venkatesan N, Finn R, Yang G, Rahmeh M, et al. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res. 2006;66(3):1630–9.PubMed
24.
Zurück zum Zitat Iqbal S, Goldman B, Fenoglio-Preiser CM, Lenz HJ, Zhang W, Danenberg KD, et al. Southwest oncology group study S0413: a phase II trial of lapatinib (GW572016) as first-line therapy in patients with advanced or metastatic gastric cancer. Ann Oncol. 2011;22(12):2610–5.PubMedPubMedCentral Iqbal S, Goldman B, Fenoglio-Preiser CM, Lenz HJ, Zhang W, Danenberg KD, et al. Southwest oncology group study S0413: a phase II trial of lapatinib (GW572016) as first-line therapy in patients with advanced or metastatic gastric cancer. Ann Oncol. 2011;22(12):2610–5.PubMedPubMedCentral
25.
Zurück zum Zitat Hecht JR, Bang YJ, Qin SK, Chung HC, Xu JM, Park JO, 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(5):443–51.PubMed Hecht JR, Bang YJ, Qin SK, Chung HC, Xu JM, Park JO, 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(5):443–51.PubMed
26.
Zurück zum Zitat Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, 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(19):2039–49.PubMed Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, 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(19):2039–49.PubMed
27.
Zurück zum Zitat Shitara K, Iwata H, Takahashi S, Tamura K, Park H, Modi S, et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Lancet Oncol. 2019;20(6):827–36.PubMed Shitara K, Iwata H, Takahashi S, Tamura K, Park H, Modi S, et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Lancet Oncol. 2019;20(6):827–36.PubMed
28.
Zurück zum Zitat Doi T, Shitara K, Naito Y, Shimomura A, Fujiwara Y, Yonemori K, et al. Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. Lancet Oncol. 2017;18(11):1512–22.PubMed Doi T, Shitara K, Naito Y, Shimomura A, Fujiwara Y, Yonemori K, et al. Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. Lancet Oncol. 2017;18(11):1512–22.PubMed
29.
Zurück zum Zitat Nordstrom JL, Gorlatov S, Zhang W, Yang Y, Huang L, Burke S, et al. Anti-tumor activity and toxicokinetics analysis of MGAH22, an anti-HER2 monoclonal antibody with enhanced Fcgamma receptor binding properties. Breast Cancer Res. 2011;13(6):R123.PubMedPubMedCentral Nordstrom JL, Gorlatov S, Zhang W, Yang Y, Huang L, Burke S, et al. Anti-tumor activity and toxicokinetics analysis of MGAH22, an anti-HER2 monoclonal antibody with enhanced Fcgamma receptor binding properties. Breast Cancer Res. 2011;13(6):R123.PubMedPubMedCentral
30.
Zurück zum Zitat Bang YJ, Giaccone G, Im SA, Oh DY, Bauer TM, Nordstrom JL, et al. First-in-human phase 1 study of margetuximab (MGAH22), an fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors. Ann Oncol. 2017;28(4):855–61.PubMedPubMedCentral Bang YJ, Giaccone G, Im SA, Oh DY, Bauer TM, Nordstrom JL, et al. First-in-human phase 1 study of margetuximab (MGAH22), an fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors. Ann Oncol. 2017;28(4):855–61.PubMedPubMedCentral
31.
Zurück zum Zitat Catenacci DVT, Park H, Lockhart AC, Gold PJ, Enzinger PC, Nordstrom JL, et al. Phase 1b/2 study of margetuximab (M) plus pembrolizumab (P) in advanced HER2+ gastroesophageal junction (GEJ) or gastric (G) adenocarcinoma (GEA). J Clin Oncol. 2018;36(4_suppl):140. Catenacci DVT, Park H, Lockhart AC, Gold PJ, Enzinger PC, Nordstrom JL, et al. Phase 1b/2 study of margetuximab (M) plus pembrolizumab (P) in advanced HER2+ gastroesophageal junction (GEJ) or gastric (G) adenocarcinoma (GEA). J Clin Oncol. 2018;36(4_suppl):140.
32.
Zurück zum Zitat Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2(2):127–37.PubMed Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2(2):127–37.PubMed
33.
Zurück zum Zitat Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, 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(6):490–9.PubMed Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, 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(6):490–9.PubMed
34.
Zurück zum Zitat Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C, 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(6):481–9.PubMedPubMedCentral Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C, 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(6):481–9.PubMedPubMedCentral
35.
Zurück zum Zitat Maron SB, Alpert L, Kwak HA, Lomnicki S, Chase L, Xu D, et al. Targeted therapies for targeted populations: anti-EGFR treatment for EGFR-amplified gastroesophageal adenocarcinoma. Cancer Discov. 2018;8(6):696–713.PubMedPubMedCentral Maron SB, Alpert L, Kwak HA, Lomnicki S, Chase L, Xu D, et al. Targeted therapies for targeted populations: anti-EGFR treatment for EGFR-amplified gastroesophageal adenocarcinoma. Cancer Discov. 2018;8(6):696–713.PubMedPubMedCentral
36.
Zurück zum Zitat Xu W, Yang Z, Lu N. Molecular targeted therapy for the treatment of gastric cancer. J Exp Clin Cancer Res. 2016;35:1.PubMedPubMedCentral Xu W, Yang Z, Lu N. Molecular targeted therapy for the treatment of gastric cancer. J Exp Clin Cancer Res. 2016;35:1.PubMedPubMedCentral
37.
Zurück zum Zitat Grigore D, Simionescu CE, Stepan A, Margaritescu C, Balasoiu M, Georgescu CC, et al. Assessment of CD105, alpha-SMA and VEGF expression in gastric carcinomas. Romanian J Morphol Embryol. 2013;54(3 Suppl):701–7. Grigore D, Simionescu CE, Stepan A, Margaritescu C, Balasoiu M, Georgescu CC, et al. Assessment of CD105, alpha-SMA and VEGF expression in gastric carcinomas. Romanian J Morphol Embryol. 2013;54(3 Suppl):701–7.
38.
Zurück zum Zitat Juttner S, Wissmann C, Jons T, Vieth M, Hertel J, Gretschel S, et al. Vascular endothelial growth factor-D and its receptor VEGFR-3: two novel independent prognostic markers in gastric adenocarcinoma. J Clin Oncol. 2006;24(2):228–40.PubMed Juttner S, Wissmann C, Jons T, Vieth M, Hertel J, Gretschel S, et al. Vascular endothelial growth factor-D and its receptor VEGFR-3: two novel independent prognostic markers in gastric adenocarcinoma. J Clin Oncol. 2006;24(2):228–40.PubMed
39.
Zurück zum Zitat Gerber HP, Ferrara N. Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res. 2005;65(3):671–80.PubMed Gerber HP, Ferrara N. Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res. 2005;65(3):671–80.PubMed
40.
Zurück zum Zitat Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, 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(30):3968–76.PubMed Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, 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(30):3968–76.PubMed
41.
Zurück zum Zitat Shen L, Li J, Xu J, Pan H, Dai G, Qin S, 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(1):168–76.PubMed Shen L, Li J, Xu J, Pan H, Dai G, Qin S, 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(1):168–76.PubMed
42.
Zurück zum Zitat Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, 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(9911):31–9.PubMed Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, 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(9911):31–9.PubMed
43.
Zurück zum Zitat • Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, 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(11):1224–35 This study resulted in the FDA approval of the first VEGF directed therapy in gastric cancer.PubMed • Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, 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(11):1224–35 This study resulted in the FDA approval of the first VEGF directed therapy in gastric cancer.PubMed
44.
Zurück zum Zitat Yoon HH, Bendell JC, Braiteh FS, Firdaus I, Philip PA, Cohn AL, et al. Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind, multicenter phase II trial. Ann Oncol. 2016;27(12):2196–203.PubMedPubMedCentral Yoon HH, Bendell JC, Braiteh FS, Firdaus I, Philip PA, Cohn AL, et al. Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind, multicenter phase II trial. Ann Oncol. 2016;27(12):2196–203.PubMedPubMedCentral
45.
Zurück zum Zitat Fuchs CS, Shitara K, Di Bartolomeo M, Lonardi S, Al-Batran SE, Van Cutsem E, et al. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(3):420–35.PubMed Fuchs CS, Shitara K, Di Bartolomeo M, Lonardi S, Al-Batran SE, Van Cutsem E, et al. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(3):420–35.PubMed
46.
Zurück zum Zitat Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, 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(13):1448–54.PubMed Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, 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(13):1448–54.PubMed
47.
Zurück zum Zitat Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, et al. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): a multinational placebo-controlled phase II trial. J Clin Oncol. 2016;34(23):2728–35.PubMedPubMedCentral Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, et al. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): a multinational placebo-controlled phase II trial. J Clin Oncol. 2016;34(23):2728–35.PubMedPubMedCentral
48.
Zurück zum Zitat Fukuoka S, Hara H, Takahashi N, Kojima T, Kawazoe A, Asayama M, et al. Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603). Journal of Clinical Oncology. 2020:JCO.19.03296. Fukuoka S, Hara H, Takahashi N, Kojima T, Kawazoe A, Asayama M, et al. Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603). Journal of Clinical Oncology. 2020:JCO.19.03296.
49.
Zurück zum Zitat Yi JH, Lee J, Lee J, Park SH, Park JO, Yim DS, et al. Randomised phase II trial of docetaxel and sunitinib in patients with metastatic gastric cancer who were previously treated with fluoropyrimidine and platinum. Br J Cancer. 2012;106(9):1469–74.PubMedPubMedCentral Yi JH, Lee J, Lee J, Park SH, Park JO, Yim DS, et al. Randomised phase II trial of docetaxel and sunitinib in patients with metastatic gastric cancer who were previously treated with fluoropyrimidine and platinum. Br J Cancer. 2012;106(9):1469–74.PubMedPubMedCentral
50.
Zurück zum Zitat Sun W, Powell M, O'Dwyer PJ, Catalano P, Ansari RH, Benson AB 3rd. 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(18):2947–51.PubMedPubMedCentral Sun W, Powell M, O'Dwyer PJ, Catalano P, Ansari RH, Benson AB 3rd. 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(18):2947–51.PubMedPubMedCentral
51.
Zurück zum Zitat Sasore T, Kennedy B. Deciphering combinations of PI3K/AKT/mTOR pathway drugs augmenting anti-angiogenic efficacy in vivo. PLoS One. 2014;9(8):e105280.PubMedPubMedCentral Sasore T, Kennedy B. Deciphering combinations of PI3K/AKT/mTOR pathway drugs augmenting anti-angiogenic efficacy in vivo. PLoS One. 2014;9(8):e105280.PubMedPubMedCentral
52.
Zurück zum Zitat Li VS, Wong CW, Chan TL, Chan AS, Zhao W, Chu KM, et al. Mutations of PIK3CA in gastric adenocarcinoma. BMC Cancer. 2005;5:29.PubMedPubMedCentral Li VS, Wong CW, Chan TL, Chan AS, Zhao W, Chu KM, et al. Mutations of PIK3CA in gastric adenocarcinoma. BMC Cancer. 2005;5:29.PubMedPubMedCentral
53.
Zurück zum Zitat Al-Batran SE, Ducreux M, Ohtsu A. mTOR as a therapeutic target in patients with gastric cancer. Int J Cancer. 2012;130(3):491–6.PubMed Al-Batran SE, Ducreux M, Ohtsu A. mTOR as a therapeutic target in patients with gastric cancer. Int J Cancer. 2012;130(3):491–6.PubMed
54.
Zurück zum Zitat Doi T, Muro K, Boku N, Yamada Y, Nishina T, Takiuchi H, et al. Multicenter phase II study of everolimus in patients with previously treated metastatic gastric cancer. J Clin Oncol. 2010;28(11):1904–10.PubMed Doi T, Muro K, Boku N, Yamada Y, Nishina T, Takiuchi H, et al. Multicenter phase II study of everolimus in patients with previously treated metastatic gastric cancer. J Clin Oncol. 2010;28(11):1904–10.PubMed
55.
Zurück zum Zitat Ohtsu A, Ajani JA, Bai YX, Bang YJ, Chung HC, Pan HM, 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(31):3935–43.PubMedPubMedCentral Ohtsu A, Ajani JA, Bai YX, Bang YJ, Chung HC, Pan HM, 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(31):3935–43.PubMedPubMedCentral
56.
Zurück zum Zitat Gherardi E, Birchmeier W, Birchmeier C, Vande WG. Targeting MET in cancer: rationale and progress. Nat Rev Cancer. 2012;12(2):89–103.PubMed Gherardi E, Birchmeier W, Birchmeier C, Vande WG. Targeting MET in cancer: rationale and progress. Nat Rev Cancer. 2012;12(2):89–103.PubMed
57.
Zurück zum Zitat Nakajima M, Sawada H, Yamada Y, Watanabe A, Tatsumi M, Yamashita J, et al. The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer. 1999;85(9):1894–902.PubMed Nakajima M, Sawada H, Yamada Y, Watanabe A, Tatsumi M, Yamashita J, et al. The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer. 1999;85(9):1894–902.PubMed
58.
Zurück zum Zitat Taniguchi K, Yonemura Y, Nojima N, Hirono Y, Fushida S, Fujimura T, et al. The relation between the growth patterns of gastric carcinoma and the expression of hepatocyte growth factor receptor (c-met), autocrine motility factor receptor, and urokinase-type plasminogen activator receptor. Cancer. 1998;82(11):2112–22.PubMed Taniguchi K, Yonemura Y, Nojima N, Hirono Y, Fushida S, Fujimura T, et al. The relation between the growth patterns of gastric carcinoma and the expression of hepatocyte growth factor receptor (c-met), autocrine motility factor receptor, and urokinase-type plasminogen activator receptor. Cancer. 1998;82(11):2112–22.PubMed
59.
Zurück zum Zitat Catenacci DVT, Tebbutt NC, Davidenko I, Murad AM, Al-Batran SE, Ilson DH, et al. Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(11):1467–82.PubMedPubMedCentral Catenacci DVT, Tebbutt NC, Davidenko I, Murad AM, Al-Batran SE, Ilson DH, et al. Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(11):1467–82.PubMedPubMedCentral
60.
Zurück zum Zitat Shah MA, Bang YJ, Lordick F, Alsina M, Chen M, Hack SP, et al. Effect of fluorouracil, leucovorin, and oxaliplatin with or without onartuzumab in HER2-negative, MET-positive gastroesophageal adenocarcinoma: the METGastric randomized clinical trial. JAMA Oncol. 2017;3(5):620–7.PubMed Shah MA, Bang YJ, Lordick F, Alsina M, Chen M, Hack SP, et al. Effect of fluorouracil, leucovorin, and oxaliplatin with or without onartuzumab in HER2-negative, MET-positive gastroesophageal adenocarcinoma: the METGastric randomized clinical trial. JAMA Oncol. 2017;3(5):620–7.PubMed
61.
62.
Zurück zum Zitat Kurz EU, Lees-Miller SP. DNA damage-induced activation of ATM and ATM-dependent signaling pathways. DNA Repair (Amst). 2004;3(8–9):889–900. Kurz EU, Lees-Miller SP. DNA damage-induced activation of ATM and ATM-dependent signaling pathways. DNA Repair (Amst). 2004;3(8–9):889–900.
63.
Zurück zum Zitat Bang YJ, Im SA, Lee KW, Cho JY, Song EK, Lee KH, 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(33):3858–65.PubMed Bang YJ, Im SA, Lee KW, Cho JY, Song EK, Lee KH, 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(33):3858–65.PubMed
64.
Zurück zum Zitat Kim HS, Kim MA, Hodgson D, Harbron C, Wellings R, O'Connor MJ, et al. Concordance of ATM (ataxia telangiectasia mutated) immunohistochemistry between biopsy or metastatic tumor samples and primary tumors in gastric cancer patients. Pathobiology. 2013;80(3):127–37.PubMed Kim HS, Kim MA, Hodgson D, Harbron C, Wellings R, O'Connor MJ, et al. Concordance of ATM (ataxia telangiectasia mutated) immunohistochemistry between biopsy or metastatic tumor samples and primary tumors in gastric cancer patients. Pathobiology. 2013;80(3):127–37.PubMed
65.
Zurück zum Zitat O'Connor MJ. Targeting the DNA damage response in cancer. Mol Cell. 2015;60(4):547–60.PubMed O'Connor MJ. Targeting the DNA damage response in cancer. Mol Cell. 2015;60(4):547–60.PubMed
66.
Zurück zum Zitat Bang YJ, Xu RH, Chin K, Lee KW, Park SH, Rha SY, et al. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(12):1637–51.PubMed Bang YJ, Xu RH, Chin K, Lee KW, Park SH, Rha SY, et al. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(12):1637–51.PubMed
67.
Zurück zum Zitat Ribas A. Tumor immunotherapy directed at PD-1. N Engl J Med. 2012;366(26):2517–9.PubMed Ribas A. Tumor immunotherapy directed at PD-1. N Engl J Med. 2012;366(26):2517–9.PubMed
68.
Zurück zum Zitat Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34.PubMedPubMedCentral Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34.PubMedPubMedCentral
69.
Zurück zum Zitat Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390(10111):2461–71.PubMed Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390(10111):2461–71.PubMed
70.
Zurück zum Zitat Janjigian YY, Bendell J, Calvo E, Kim JW, Ascierto PA, Sharma P, et al. CheckMate-032 study: efficacy and safety of nivolumab and nivolumab plus ipilimumab in patients with metastatic esophagogastric cancer. J Clin Oncol. 2018;36(28):2836–44.PubMedPubMedCentral Janjigian YY, Bendell J, Calvo E, Kim JW, Ascierto PA, Sharma P, et al. CheckMate-032 study: efficacy and safety of nivolumab and nivolumab plus ipilimumab in patients with metastatic esophagogastric cancer. J Clin Oncol. 2018;36(28):2836–44.PubMedPubMedCentral
71.
Zurück zum Zitat Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, et al. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018;4(5):e180013.PubMedPubMedCentral Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, et al. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018;4(5):e180013.PubMedPubMedCentral
72.
Zurück zum Zitat • Shitara K, Ozguroglu M, Bang YJ, Di Bartolomeo M, Mandala M, Ryu MH, et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018;392(10142):123–33 This study resulted in the FDA approval of the first immune therapy in gastric cancer.PubMed • Shitara K, Ozguroglu M, Bang YJ, Di Bartolomeo M, Mandala M, Ryu MH, et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018;392(10142):123–33 This study resulted in the FDA approval of the first immune therapy in gastric cancer.PubMed
73.
Zurück zum Zitat Kojima T, Muro K, Francois E, Hsu C-H, Moriwaki T, Kim S-B, et al. Pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer: phase III KEYNOTE-181 study. J Clin Oncol. 2019;37(4_suppl):2. Kojima T, Muro K, Francois E, Hsu C-H, Moriwaki T, Kim S-B, et al. Pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer: phase III KEYNOTE-181 study. J Clin Oncol. 2019;37(4_suppl):2.
74.
Zurück zum Zitat Tabernero J, Cutsem EV, Bang Y-J, Fuchs CS, Wyrwicz L, Lee KW, et al. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. J Clin Oncol. 2019;37(18_suppl):LBA4007–LBA. Tabernero J, Cutsem EV, Bang Y-J, Fuchs CS, Wyrwicz L, Lee KW, et al. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. J Clin Oncol. 2019;37(18_suppl):LBA4007–LBA.
75.
Zurück zum Zitat Chung HC, Arkenau HT, Lee J, Rha SY, Oh DY, Wyrwicz L, et al. Avelumab (anti-PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN solid tumor trial. J Immunother Cancer. 2019;7(1):30.PubMedPubMedCentral Chung HC, Arkenau HT, Lee J, Rha SY, Oh DY, Wyrwicz L, et al. Avelumab (anti-PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN solid tumor trial. J Immunother Cancer. 2019;7(1):30.PubMedPubMedCentral
76.
Zurück zum Zitat Doi T, Iwasa S, Muro K, Satoh T, Hironaka S, Esaki T, et al. Phase 1 trial of avelumab (anti-PD-L1) in Japanese patients with advanced solid tumors, including dose expansion in patients with gastric or gastroesophageal junction cancer: the JAVELIN solid tumor JPN trial. Gastric Cancer. 2019;22(4):817–27.PubMed Doi T, Iwasa S, Muro K, Satoh T, Hironaka S, Esaki T, et al. Phase 1 trial of avelumab (anti-PD-L1) in Japanese patients with advanced solid tumors, including dose expansion in patients with gastric or gastroesophageal junction cancer: the JAVELIN solid tumor JPN trial. Gastric Cancer. 2019;22(4):817–27.PubMed
77.
Zurück zum Zitat Bang YJ, Ruiz EY, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, et al. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN gastric 300. Ann Oncol. 2018;29(10):2052–60.PubMedPubMedCentral Bang YJ, Ruiz EY, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, et al. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN gastric 300. Ann Oncol. 2018;29(10):2052–60.PubMedPubMedCentral
Metadaten
Titel
Targeted Therapies in Advanced Gastric Cancer
verfasst von
Timil H. Patel, MD
Michael Cecchini, MD
Publikationsdatum
01.09.2020
Verlag
Springer US
Erschienen in
Current Treatment Options in Oncology / Ausgabe 9/2020
Print ISSN: 1527-2729
Elektronische ISSN: 1534-6277
DOI
https://doi.org/10.1007/s11864-020-00774-4

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