Abstract
In the past 10 years, advanced gastroesophageal cancers have finally garnered precision medicine approaches with currently recommended testing of HER2, MSI, and PD-L1 tumor biomarkers. The latter two only recently emerged in the past 2 years, and PD-L1 determination still remains imperfect with questions remaining on optimal cutoff levels and if timing of tumor sampling matters with the dynamic nature of activation of immune pathways. Ongoing clinical trial efforts will provide some answers to these questions as immuno-oncology approaches are being increasingly integrated into earlier lines of treatment. To develop further biomarkers for novel molecularly targeted therapies, spatial and temporal intra-patient tumoral heterogeneity will need to be better understood in order to inhibit shifting oncogenic signaling pathways that occurs with clonal evolution and development of therapeutic resistance. Such composite testing strategies can hopefully be brought to fruition as newer technologies enabling single cell and serial ctDNA analyses are realized in the clinic.
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References
American_Cancer_Society. Global cancer facts & figures. 3rd ed. Atlanta: American Cancer Society; 2015.
Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008;19(9):1523–9.
Bartley AN, 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.
Dong H, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793–800.
Bang YJ, 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.
Bartley AN, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline summary from the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology. J Oncol Pract. 2017;13(1):53–7.
Peddi PF, Hurvitz SA. Trastuzumab emtansine: the first targeted chemotherapy for treatment of breast cancer. Future Oncol. 2013;9(3):319–26.
Thuss-Patience PC, 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.
Kang YK, 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.
Wainberg ZA, et al. LBA28_PRKEYNOTE-059 update: efficacy and safety of pembrolizumab alone or in combination with chemotherapy in patients with advanced gastric or gastroesophageal (G/GEJ) cancer. Ann Oncol. 2017;28(suppl_5):mdx440.020-mdx440.020.
Fuchs CS, 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.
Janjigian YY, 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.
Shitara K, 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.
Llosa NJ, et al. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov. 2015;5(1):43.
Le DT, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20.
Comoglio PM, et al. Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nat Rev Drug Discov. 2008;7(6):504–16.
Catenacci DVT, 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.
Shah MA, 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.
Kang YK, et al. A phase II trial of a selective c-Met inhibitor tivantinib (ARQ 197) monotherapy as a second- or third-line therapy in the patients with metastatic gastric cancer. Investig New Drugs. 2014;32(2):355–61.
Kim M, et al. EGFR in gastric carcinomas: prognostic significance of protein overexpression and high gene copy number. Histopathology. 2008;52(6):738–46.
Lordick F, 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.
Waddell T, 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.
Pectasides E, et al. Genomic heterogeneity as a barrier to precision medicine in gastroesophageal adenocarcinoma. Cancer Discov. 2018;8(1):37–48.
Kwak EL, et al. Molecular heterogeneity and receptor coamplification drive resistance to targeted therapy in MET-amplified esophagogastric cancer. Cancer Discov. 2015;5(12):1271–81.
Maron SB, et al. Targeted therapies for targeted populations: anti-EGFR treatment for EGFR-amplified gastroesophageal adenocarcinoma. Cancer Discov. 2018;8(6):696–713.
Kim ST, et al. Impact of genomic alterations on lapatinib treatment outcome and cell-free genomic landscape during HER2 therapy in HER2+ gastric cancer patients. Ann Oncol. 2018;29(4):1037–48.
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Jang, M.J., Chao, J. (2020). Esophageal and Gastric Cancer. In: Salgia, R. (eds) Oncology in the Precision Medicine Era. Springer, Cham. https://doi.org/10.1007/978-3-030-31471-2_3
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DOI: https://doi.org/10.1007/978-3-030-31471-2_3
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