Esophageal and Esophagogastric Junction Cancers

Regimen Options

Last Updated: 07/18/2025 See Details

NOTE: For trastuzumab, the use of a biosimilar trastuzumab (eg. Kanjinti) is on pathway

	Evolent Pathways	Febrile Neutropenic Risk	Emetogenic Risk	References
NON-METASTATIC
Neoadjuvant	carboplatin and paclitaxel	Low	High	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. van Meerten E, et al. Br J Cancer. 2006;94(10):1389-94. Noordman BJ, et al. J Clin Oncol. 2017;JCO2017737718.
Adjuvant (postoperative therapy)	nivolumab	Low	Low	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. Kelly RJ et al. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med 2021; 384:1191-1203
Perioperative Chemotherapy	oxaliplatin and 5FU (fluorouracil)	Low	Moderate	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. Kushalani NI, et al. J Clin Oncol. 2002;20(12):2844-50.
	oxaliplatin and capecitabine	Low	Moderate	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. Javle MM, et al. Cancer Invest. 2009;27(2):193-200.
	cisplatin and 5FU (fluorouracil)	Low	High	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. Ychou M et al. J Clin Oncol . 2011 May 1;29(13):1715-21
	FLOT (5FU, Leucovorin, Oxaliplatin, Docetaxel)	Low	Moderate	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. Al-Batran SE, et al. Lancet Oncol.Lancet Oncol. 2016 Dec;17(12):1697-1708.
METASTATIC
Initial Therapy (ECOG PS ≤ 2)	capecitabine, oxaliplatin and trastuzumab if HER2+, adenocarcinoma only	Low	Moderate	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. Bang YJ, et al. Lancet. 2010;376(9742):687-97. Sawaki A, et al. Gastric Cancer. 2012;15(3):313-22.
	5FU (fluorouracil), leucovorin, oxaliplatin and trastuzumab if HER2+, adenocarcinoma only	Intermediate	Moderate	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. Bang YJ, et al. Lancet. 2010;376(9742):687-97. Sawaki A, et al. Gastric Cancer. 2012;15(3):313-22.
	cisplatin and 5FU (fluorouracil)	Low	High	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. Lorenzen S, et al. Ann of Oncol. 2009;20(10):1667-73.
	cisplatin and capecitabine	Low	High	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. Kang Y, et al. Ann Oncol. 2009;20(4):666-673. Lee SJ, et al. BMC Cancer. 2015;15:693.
	FOLFOX (leucovorin, fluorouracil, and oxaliplatin)	Intermediate	Moderate	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. Al-Batran SE, et al. J Clin Oncol. 2008;26(9):1435-42. Lorenzen S, et al. Br J Cancer. 2013;108(3):519-26.
	CAPEOX (capecitabine, oxaliplatin)	Low	Moderate	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. van Meerten E, et al. Br J Cancer. 2007;96(9):1348-52. Kim GM, et al. Eur J Cancer. 2012;48(4):518-26. Cunningham D, et al. N Engl J Med. 2008;358(1):36-46.
	nivolumab and CAPEOX (capecitabine, oxaliplatin) CPS ≥5, adenocarcinoma only	Low	Moderate	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. Janjigan YY et al. Lancet. 2021 Jul 3; 398(10294): 27–40.
	nivolumab and FOLFOX (leucovorin, fluorouracil, and oxaliplatin) CPS ≥5, adenocarcinoma only	Intermediate	Moderate	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. Janjigan YY et al. Lancet. 2021 Jul 3; 398(10294): 27–40.
	nivolumab, fluorouracil and cisplatin CPS ≥1, squamous only	Low	High	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. v.3.2022. Doki Y, et al. N Engl J Med 2022; 386:449-462
	pembrolizumab, cisplatin or oxaliplatin and fluorouracil or capecitabine PD-L1 CPS ≥ 10	Low	Moderate	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. v.2.2025. Sun JM, et al. Lancet 2021; 398: 759–771 Rha, SY et al. Lancet Oncol. 2023 Nov;24(11):1181-1195.
	fluorouracil or capecitabine, oxaliplatin, trastuzumab and pembrolizumab (PD-L1 CPS ≥1) HER2 positive	Low	High	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. v.3.2025. Janjigan YY et al. N Engl J Med. 2024 Oct 10;391(14):1360-1362.
	fluorouracil or capecitabine, cisplatin, trastuzumab and pembrolizumab (PD-L1 CPS ≥1) HER2 positive	Low	High	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. v.3.2025. Janjigan YY et al. N Engl J Med. 2024 Oct 10;391(14):1360-1362.
Subsequent Therapy	paclitaxel	Low	Low	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. Ilson DH, et al. Ann Oncol. 2007;18(5):898-902. Shitara K, et al. Jpn J Clin Oncol. 2011;41(2):287-90. Ajani JA, et al. J Natl Cancer Inst. 1994;86(14):1086-91.
	docetaxel	Low	Low	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. Albertsson M, et al. Med Oncol. 2007;24(4):407-12.
	irinotecan	Low	Moderate	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. Thuss-Patience PC, et al. Eur J Cancer. 2011;47(15):2306-14. Fuchs CS, et al. J Clin Oncol. 2003;21(5):807-14. Cunningham D, et al. N Engl J Med. 2004;351(4):337-45.
	irinotecan and 5FU (fluorouracil)	Low	Moderate	NCCN Guidelines® for Esophageal and Esophagogastric Junction Cancers. V.4.2017. Wolff k, et al. Anticancer Drugs.2009;20(3):165-73
	fam-trastuzumab deruxtecan-nxki if HER2 positive	Low	Moderate	NCCN Guidelines® for Gastric Cancer V.4.2017. Shitara K et al. N Engl J Med 2020; 382:2419-2430
	Best Supportive Care or Clinical Trial	Not Applicable	Not applicable	Best Supportive Care or Clinical Trial

NON-METASTATIC

Neoadjuvant

Evolent Pathways

carboplatin and paclitaxel

Febrile Neutropenic Risk

low

Emetogenic Risk

high

References

Adjuvant (postoperative therapy)

Evolent Pathways

nivolumab

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Perioperative Chemotherapy

Evolent Pathways

oxaliplatin and 5FU (fluorouracil)

Febrile Neutropenic Risk

low

Emetogenic Risk

moderate

References

Evolent Pathways

oxaliplatin and capecitabine

Febrile Neutropenic Risk

low

Emetogenic Risk

moderate

References

Evolent Pathways

cisplatin and 5FU (fluorouracil)

Febrile Neutropenic Risk

low

Emetogenic Risk

high

References

Evolent Pathways

FLOT (5FU, Leucovorin, Oxaliplatin, Docetaxel)

Febrile Neutropenic Risk

low

Emetogenic Risk

moderate

References

METASTATIC

Initial Therapy (ECOG PS ≤ 2)

Evolent Pathways

capecitabine, oxaliplatin and trastuzumab *if HER2+, adenocarcinoma only*

Febrile Neutropenic Risk

low

Emetogenic Risk

moderate

References

Evolent Pathways

5FU (fluorouracil), leucovorin, oxaliplatin and trastuzumab *if HER2+, adenocarcinoma only*

Febrile Neutropenic Risk

intermediate

Emetogenic Risk

moderate

References

Evolent Pathways

cisplatin and 5FU (fluorouracil)

Febrile Neutropenic Risk

low

Emetogenic Risk

high

References

Evolent Pathways

cisplatin and capecitabine

Febrile Neutropenic Risk

low

Emetogenic Risk

high

References

Evolent Pathways

FOLFOX (leucovorin, fluorouracil, and oxaliplatin)

Febrile Neutropenic Risk

intermediate

Emetogenic Risk

moderate

References

Evolent Pathways

CAPEOX (capecitabine, oxaliplatin)

Febrile Neutropenic Risk

low

Emetogenic Risk

moderate

References

Evolent Pathways

nivolumab and CAPEOX (capecitabine, oxaliplatin) *CPS ≥5, adenocarcinoma only*

Febrile Neutropenic Risk

low

Emetogenic Risk

moderate

References

Evolent Pathways

nivolumab and FOLFOX (leucovorin, fluorouracil, and oxaliplatin) *CPS ≥5, adenocarcinoma only*

Febrile Neutropenic Risk

intermediate

Emetogenic Risk

moderate

References

Evolent Pathways

nivolumab, fluorouracil and cisplatin *CPS ≥1, squamous only*

Febrile Neutropenic Risk

low

Emetogenic Risk

high

References

Evolent Pathways

pembrolizumab, cisplatin or oxaliplatin and fluorouracil or capecitabine *PD-L1 CPS ≥ 10*

Febrile Neutropenic Risk

low

Emetogenic Risk

moderate

References

Evolent Pathways

fluorouracil or capecitabine, oxaliplatin, trastuzumab and pembrolizumab (PD-L1 CPS ≥1) *HER2 positive*

Febrile Neutropenic Risk

low

Emetogenic Risk

high

References

Evolent Pathways

fluorouracil or capecitabine, cisplatin, trastuzumab and pembrolizumab (PD-L1 CPS ≥1) *HER2 positive*

Febrile Neutropenic Risk

low

Emetogenic Risk

high

References

Subsequent Therapy

Evolent Pathways

paclitaxel

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

docetaxel

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

irinotecan

Febrile Neutropenic Risk

low

Emetogenic Risk

moderate

References

Evolent Pathways

irinotecan and 5FU (fluorouracil)

Febrile Neutropenic Risk

low

Emetogenic Risk

moderate

References

Evolent Pathways

fam-trastuzumab deruxtecan-nxki *if HER2 positive*

Febrile Neutropenic Risk

low

Emetogenic Risk

moderate

References

Evolent Pathways

Best Supportive Care or Clinical Trial

Febrile Neutropenic Risk

Emetogenic Risk

References

Pathways and Low-Value Regimens

Esophageal and Esophagogastric Junction Cancers