Nivolumab Adjuvant Therapy for Esophageal Cancer: a Review Based on Subgroup Analysis of CheckMate 577 Trial

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Oct 20

PMID 37860010

Authors

Yan Lin

Huan-Wei Liang

Yang Liu

Xin-Bin Pan

Affiliations

Soon will be listed here.

Abstract

Esophageal cancer is the sixth most common cancer worldwide. Approximately 50% of patients have locally advanced disease. The CROSS and NEOCRTEC5010 trials have demonstrated that neoadjuvant chemoradiotherapy followed by surgery is the standard treatment for patients with resectable disease. However, a pathological complete response is frequently not achieved, and most patients have a poor prognosis. The CheckMate 577 trial demonstrates that nivolumab adjuvant therapy improves disease-free survival in patents without a pathological complete response. However, there are still numerous clinical questions of concern that remain controversial based on the results of the subgroup analysis. In this review, we aim to offer constructive suggestions addressing the clinical concerns raised in the CheckMate 577 trial.

Citing Articles

Immune microenvironment features underlying the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy in local advanced gastric cancer.

Zhang N, Li C, Zhao Z, Jiang B, Wang W, Sun F Front Immunol. 2025; 16:1497004.

PMID: 39931056 PMC: 11808021. DOI: 10.3389/fimmu.2025.1497004.

Effects of chemoradiotherapy on surface PD-L1 expression in esophageal cancer and its implications for immunotherapy.

Hampe L, Kuffer S, Niemeier T, Scheele N, Hampe L, Riedl A Front Immunol. 2025; 15:1509051.

PMID: 39763660 PMC: 11701229. DOI: 10.3389/fimmu.2024.1509051.

Therapeutic efficacy of immunotherapy for gastric cancer metastasis.

Xie F, Qian S, Zhao H, Liu Q World J Gastrointest Surg. 2024; 16(12):3881-3886.

PMID: 39734465 PMC: 11650231. DOI: 10.4240/wjgs.v16.i12.3881.

Equivalent prognosis with no lymph node metastasis to pathological complete remission in patients with localized advanced esophageal cancer after neoadjuvant triplet chemotherapy with docetaxel, cisplatin, and 5-fluorouracil followed by curative....

Chinen T, Yamaguchi H, Ohzawa H, Matsumoto S, Kurashina K, Saito S J Thorac Dis. 2024; 16(1):391-400.

PMID: 38410613 PMC: 10894374. DOI: 10.21037/jtd-23-1484.

References

Lauret Marie Joseph E, Kirilovsky A, Lecoester B, El Sissy C, Boullerot L, Rangan L . Chemoradiation triggers antitumor Th1 and tissue resident memory-polarized immune responses to improve immune checkpoint inhibitors therapy. J Immunother Cancer. 2021; 9(7). PMC: 8261891. DOI: 10.1136/jitc-2020-002256. View

Stewart M, Norden A, Dreyer N, Joe Henk H, Abernethy A, Chrischilles E . An Exploratory Analysis of Real-World End Points for Assessing Outcomes Among Immunotherapy-Treated Patients With Advanced Non-Small-Cell Lung Cancer. JCO Clin Cancer Inform. 2019; 3:1-15. PMC: 6873914. DOI: 10.1200/CCI.18.00155. View

Salem M, Puccini A, Xiu J, Raghavan D, Lenz H, Korn W . Comparative Molecular Analyses of Esophageal Squamous Cell Carcinoma, Esophageal Adenocarcinoma, and Gastric Adenocarcinoma. Oncologist. 2018; 23(11):1319-1327. PMC: 6291329. DOI: 10.1634/theoncologist.2018-0143. View

Hipp J, Nagavci B, Schmoor C, Meerpohl J, Hoeppner J, Schmucker C . Post-Neoadjuvant Surveillance and Surgery as Needed Compared with Post-Neoadjuvant Surgery on Principle in Multimodal Treatment for Esophageal Cancer: A Scoping Review. Cancers (Basel). 2021; 13(3). PMC: 7865772. DOI: 10.3390/cancers13030429. View

Yang Y, Xu X, Zhou X, Bao W, Zhang D, Gu F . Impact of Radiation Dose on Survival for Esophageal Squamous Cell Carcinoma Treated With Neoadjuvant Chemoradiotherapy. Front Oncol. 2020; 10:1431. PMC: 7468494. DOI: 10.3389/fonc.2020.01431. View

Deng L, Liang H, Burnette B, Beckett M, Darga T, Weichselbaum R . Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 2014; 124(2):687-95. PMC: 3904601. DOI: 10.1172/JCI67313. View

Robb W, Messager M, Dahan L, Mornex F, Maillard E, DJourno X . Patterns of recurrence in early-stage oesophageal cancer after chemoradiotherapy and surgery compared with surgery alone. Br J Surg. 2015; 103(1):117-25. DOI: 10.1002/bjs.9959. View

Ajani J, Xiao L, Roth J, Hofstetter W, Walsh G, Komaki R . A phase II randomized trial of induction chemotherapy versus no induction chemotherapy followed by preoperative chemoradiation in patients with esophageal cancer. Ann Oncol. 2013; 24(11):2844-9. PMC: 3937600. DOI: 10.1093/annonc/mdt339. View

Chao Y, Chan S, Liu Y, Chen H, Wan Y, Chang H . Pretreatment T3-4 stage is an adverse prognostic factor in patients with esophageal squamous cell carcinoma who achieve pathological complete response following preoperative chemoradiotherapy. Ann Surg. 2009; 249(3):392-6. DOI: 10.1097/SLA.0b013e3181949e9f. View

10.

Lin S, Lin Y, Yao L, Kalhor N, Carter B, Altan M . Phase II Trial of Concurrent Atezolizumab With Chemoradiation for Unresectable NSCLC. J Thorac Oncol. 2019; 15(2):248-257. DOI: 10.1016/j.jtho.2019.10.024. View

11.

Huang Bartlett C, Mardekian J, Cotter M, Huang X, Zhang Z, Parrinello C . Concordance of real-world versus conventional progression-free survival from a phase 3 trial of endocrine therapy as first-line treatment for metastatic breast cancer. PLoS One. 2020; 15(4):e0227256. PMC: 7173855. DOI: 10.1371/journal.pone.0227256. View

12.

Engel S, Awerbuch A, Kwon D, Picado O, Yechieli R, Yakoub D . Optimal radiation dosing in concurrent neoadjuvant chemoradiation for resectable esophageal cancer: a meta-analysis. J Gastrointest Oncol. 2019; 10(3):391-399. PMC: 6534709. DOI: 10.21037/jgo.2019.01.02. View

13.

Pottgen C, Stuschke M . Radiotherapy versus surgery within multimodality protocols for esophageal cancer--a meta-analysis of the randomized trials. Cancer Treat Rev. 2011; 38(6):599-604. DOI: 10.1016/j.ctrv.2011.10.005. View

14.

Li C, Wang X, Wang L, Chen J, Zhang W, Pang Q . Clinical practice and outcome of radiotherapy for advanced esophageal squamous cell carcinoma between 2002 and 2018 in China: the multi-center 3JECROG Survey. Acta Oncol. 2021; 60(5):627-634. DOI: 10.1080/0284186X.2021.1902564. View

15.

Antonia S, Villegas A, Daniel D, Vicente D, Murakami S, Hui R . Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017; 377(20):1919-1929. DOI: 10.1056/NEJMoa1709937. View

16.

Lagergren J, Smyth E, Cunningham D, Lagergren P . Oesophageal cancer. Lancet. 2017; 390(10110):2383-2396. DOI: 10.1016/S0140-6736(17)31462-9. View

17.

Matsuda S, Kawakubo H, Okamura A, Takahashi K, Toihata T, Takemura R . Distribution of Residual Disease and Recurrence Patterns in Pathological Responders After Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma. Ann Surg. 2020; 276(2):298-304. DOI: 10.1097/SLA.0000000000004436. View

18.

Buckstein M, Rhome R, Ru M, Moshier E . Neoadjuvant chemoradiation radiation dose levels for surgically resectable esophageal cancer: predictors of use and outcomes. Dis Esophagus. 2018; 31(5). PMC: 5993676. DOI: 10.1093/dote/dox148. View

19.

Klevebro F, Nilsson K, Lindblad M, Ekman S, Johansson J, Lundell L . Association between time interval from neoadjuvant chemoradiotherapy to surgery and complete histological tumor response in esophageal and gastroesophageal junction cancer: a national cohort study. Dis Esophagus. 2019; 33(5). PMC: 7203996. DOI: 10.1093/dote/doz078. View

20.

van Hagen P, Wijnhoven B, Nafteux P, Moons J, Haustermans K, De Hertogh G . Recurrence pattern in patients with a pathologically complete response after neoadjuvant chemoradiotherapy and surgery for oesophageal cancer. Br J Surg. 2012; 100(2):267-73. DOI: 10.1002/bjs.8968. View