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Table of Contents
Year : 2020  |  Volume : 3  |  Issue : 1  |  Page : 130-131

Systemic therapy in metastatic esophageal malignancies - time to move away from ‘one size fits all (histologies)’

Department of Oncology, KMCH, Coimbatore, Tamil Nadu, India

Date of Submission13-Jan-2020
Date of Acceptance14-Jan-2020
Date of Web Publication24-Feb-2020

Correspondence Address:
Ram Abhinav Kannan
Department of Oncology, KMCH, 99, Avinashi Rd., TNHB Colony, Indira Nagar, Civil Aerodrome Post, Peelamedu, Coimbatore - 641 014, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/CRST.CRST_22_20

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How to cite this article:
Kannan RA, Rangarajan B. Systemic therapy in metastatic esophageal malignancies - time to move away from ‘one size fits all (histologies)’. Cancer Res Stat Treat 2020;3:130-1

How to cite this URL:
Kannan RA, Rangarajan B. Systemic therapy in metastatic esophageal malignancies - time to move away from ‘one size fits all (histologies)’. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Mar 30];3:130-1. Available from: http://www.crstonline.com/text.asp?2020/3/1/130/279100

Management of advanced esophageal cancer has been controversial for long. This review article is an excellent summary of the evolution of therapy over the past five decades to the contemporary management of advanced esophageal cancers.[1] The benefits of chemotherapy, targeted therapy, and immunotherapy have been well summarized. It is now evident that research conducted recently in the treatment of advanced esophageal cancer is mostly for adenocarcinoma histology, while the initial studies conducted focused primarily on squamous cell carcinomas (SCCs).

SCC patients form a minority of the patients in the present era at least in the Western literature and it is now becoming increasingly clear that there are differences in genomic alterations in the biologic pathways between SCC and adenocarcinoma.[2] This review article did not attempt to distinguish therapies which are not appropriate for SCC patients. Conventionally, fluoropyrimidine and platinum-based combination chemotherapy regimens have formed the backbone for systemic therapy in esophageal carcinoma irrespective of histology. However, over time metastatic esophageal adenocarcinomas have been increasingly treated with therapies targeting human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF), similar to the treatments being used in metastatic gastric adenocarcinoma.

Although this review comprehensively explains the benefits of each therapy, it does not provide clarity on the factors guiding the choice of therapy in first and subsequent lines, from the exhaustive list of options. Nor does it suggest the ideal first-line therapy, settings where single agent, doublet chemotherapy vis-à-vis triplet chemotherapy should be utilized. The choice of agents/regimens based on the histology and the benefits thereof is not discussed.

In patients with advanced HER2-positive gastric or esophageal adenocarcinomas, the addition of trastuzumab to a cytotoxic chemotherapy backbone is the preferred first-line therapy. For patients with non-HER2-expressing adenocarcinomas or SCC, the choice of the initial regimen is empiric. For these patients, we suggest a fluoropyrimidine-platinum doublet over a triplet regimen. Meta-analysis suggests a benefit for oxaliplatin and fluoropyrimidine doublet when used as a partner of trastuzumab in gastric adenocarcinoma.[3] A triplet chemotherapy regimen may be appropriate for patients with HER2/neu-negative tumors, good performance status and those willing to accept the higher treatment-related toxicity for possible longer progression-free survival.

We now have data that checkpoint inhibitors can be utilized in the first-line setting in HER2-negative, advanced esophageal cancers. In the Phase III study, KEYNOTE -062, 763 patients with untreated, advanced, gastric or esophagogastric junction adenocarcinomas with a CPS ≥1 were randomly assigned to pembrolizumab alone, chemotherapy alone (cisplatin plus a fluoropyrimidine), or combined therapy. At a median follow-up of 11.3 months, pembrolizumab was noninferior to chemotherapy alone for overall survival which was the primary endpoint (median 10.6 vs. 11.1 months, and it was associated with fewer any grade (54% vs. 92%) and Grade 3 or 4 (16% vs. 68%) adverse effects.[4] The use of immunotherapy in the second and subsequent lines may be empiric or biomarker-driven with programmed death-ligand 1, microsatellite instability status, and tumor mutational burden being some of the tests used. However, there is still no robust marker to predict responses in the majority of patients.

Although the addition of cetuximab or panitumumab did not result in improvement in survival, none of these trials selected patients based on biomarkers. We know from colorectal cancers that the benefit of these agents is limited to patients whose tumors lack mutated RAS genes. These agents may still be useful in a subset of patients, and this could be an area of active research in future.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Simha V, Patil V, Joshi A, Prabhash K, Noronha V. Role of palliative chemotherapy and targeted therapy in advanced esophageal and gastroesophageal junction cancers. Cancer Res Statist Treat 2019;2:172-81.  Back to cited text no. 1
Wang K, Johnson A, Ali SM, Klempner SJ, Bekaii-Saab T, Vacirca JL, et al. Comprehensive genomic profiling of advanced esophageal squamous cell carcinomas and esophageal adenocarcinomas reveals similarities and differences. Oncologist 2015;20:1132-9.  Back to cited text no. 2
Ter Veer E, Creemers A, de Waal L, van Oijen MG, van Laarhoven HW. Comparing cytotoxic backbones for first-line trastuzumab-containing regimens in human epidermal growth factor receptor 2-positive advanced oesophagogastric cancer: A meta-analysis. Int J Cancer 2018;143:438-48.  Back to cited text no. 3
Tabernero J, Cutsem EV, Bang YJ, 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.  Back to cited text no. 4


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