Tislelizumab Plus Chemotherapy Sequential Neoadjuvant Therapy for Non-cCR Patients After Neoadjuvant Chemoradiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma (ETNT): An Exploratory Study

Wenwu He, Chenghao Wang, Lei Wu, Gang Wan, Baisen Li, Yongtao Han, Haojun Li, Xuefeng Leng, Kunyi Du, Haijun Chen, Qifeng Wang, Lin Peng, Wenwu He, Chenghao Wang, Lei Wu, Gang Wan, Baisen Li, Yongtao Han, Haojun Li, Xuefeng Leng, Kunyi Du, Haijun Chen, Qifeng Wang, Lin Peng

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) remains a challenging malignant tumor with poor prognosis and limited treatment methods worldwide, and most patients are at a locally advanced stage at diagnosis. High recurrence and metastasis rates remain the main factors leading to the failure of the current standard treatment of neoadjuvant chemoradiotherapy plus surgery for resectable locally advanced ESCC. Improving the pathological complete response (pCR) rate may significantly benefit the survival of patients with resectable locally advanced ESCC after neoadjuvant therapy.

Methods: Tislelizumab plus sequential neoadjuvant chemotherapy was administered to non-clinical complete response (cCR) patients after neoadjuvant chemoradiotherapy for locally advanced ESCC. The patients then received surgery and adjuvant therapy according to the postoperative pathological results. Eighty patients with locally advanced ESCC were recruited for the study. The primary outcomes of the pCR rate and the incidence of adverse events will be analyzed completely within 24 months, and the secondary endpoints will include cCR rate, major pathological response rate, objective response rate, R0 resection rate, event-free survival, and overall survival.

Discussion: This study explored the safety and efficacy of tislelizumab plus chemotherapy sequential neoadjuvant therapy for non-cCR patients and provided a total neoadjuvant therapy model that can benefit patients with locally advanced ESCC.

Clinical trial registration: ClinicalTrials. gov NCT05189730. Registered: November 26, 2021, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BBD5&selectaction=Edit&uid=U0004UG3&ts=47&cx=e0cm59.

Keywords: esophageal squamous cell carcinoma; neoadjuvant chemoimmunotherapy; neoadjuvant chemoradiotherapy; protocol; tislelizumab; total neoadjuvant therapy.

Conflict of interest statement

Author HC was employed by BeiGene (Beijing) Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 He, Wang, Wu, Wan, Li, Han, Li, Leng, Du, Chen, Wang and Peng.

Figures

Figure 1
Figure 1
Flowchart of the exploratory study. ESCC, esophageal squamous cell carcinoma; cCR, clinical complete response; cPD, clinical progressive disease; cPR, clinical partial response; cSD, clinical stable disease; MDT, multidisciplinary team; pCR, pathology complete response.

References

    1. 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. doi: 10.3322/caac.21492
    1. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. . Cancer Statistics in China, 2015. CA Cancer J Clin (2016) 66(2):115–32. doi: 10.3322/caac.21338
    1. Arnold M, Abnet CC, Neale RE, Vignat J, Giovannucci EL, McGlynn KA, et al. . Global Burden of 5 Major Types of Gastrointestinal Cancer. Gastroenterology (2020) 159(1):335–49 e15. doi: 10.1053/j.gastro.2020.02.068
    1. van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, et al. . Preoperative Chemoradiotherapy for Esophageal or Junctional Cancer. N Engl J Med (2012) 366(22):2074–84. doi: 10.1056/NEJMoa1112088
    1. Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, et al. . Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial. J Clin Oncol (2018) 36(27):2796–803. doi: 10.1200/JCO.2018.79.1483
    1. Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, et al. . Long-Term Efficacy of Neoadjuvant Chemoradiotherapy Plus Surgery for the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma: The NEOCRTEC5010 Randomized Clinical Trial. JAMA Surg (2021) 156(8):721–9. doi: 10.1001/jamasurg.2021.2373
    1. Eyck BM, van Lanschot JJB, Hulshof M, van der Wilk BJ, Shapiro J, van Hagen P, et al. . Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial. J Clin Oncol (2021) 39(18):1995–2004. doi: 10.1200/JCO.20.03614
    1. Shen J, Kong M, Yang H, Jin K, Chen Y, Fang W, et al. . Pathological Complete Response After Neoadjuvant Treatment Determines Survival in Esophageal Squamous Cell Carcinoma Patients (NEOCRTEC5010). Ann Transl Med (2021) 9(20):1516. doi: 10.21037/atm-21-3331
    1. Satoh T, Kato K, Ura T, Hamamoto Y, Kojima T, Tsushima T, et al. . Five-Year Follow-Up of Nivolumab Treatment in Japanese Patients With Esophageal Squamous-Cell Carcinoma (ATTRACTION-1/ONO-4538-07). Esophagus (2021) 18(4):835–43. doi: 10.1007/s10388-021-00850-0
    1. Kojima T, Shah MA, Muro K, Francois E, Adenis A, Hsu CH, et al. . Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer. J Clin Oncol (2020) 38(35):4138–48. doi: 10.1200/JCO.20.01888
    1. Kato K, Cho BC, Takahashi M, Okada M, Lin CY, Chin K, et al. . Nivolumab Versus Chemotherapy in Patients With Advanced Oesophageal Squamous Cell Carcinoma Refractory or Intolerant to Previous Chemotherapy (ATTRACTION-3): A Multicentre, Randomised, Open-Label, Phase 3 Trial. Lancet Oncol (2019) 20(11):1506–17. doi: 10.1016/S1470-2045(19)30626-6
    1. Shah MA, Kojima T, Hochhauser D, Enzinger P, Raimbourg J, Hollebecque A, et al. . Efficacy and Safety of Pembrolizumab for Heavily Pretreated Patients With Advanced, Metastatic Adenocarcinoma or Squamous Cell Carcinoma of the Esophagus: The Phase 2 KEYNOTE-180 Study. JAMA Oncol (2019) 5(4):546–50. doi: 10.1001/jamaoncol.2018.5441
    1. Zheng Y, Liu XB, Sun HB, Xu J, Shen S, Ba YF, et al. . A Phase III Study on Neoadjuvant Chemotherapy Versus Neoadjuvant Toripalimab Plus Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: Henan Cancer Hospital Thoracic Oncology Group 1909 (Hchtog1909). Ann Transl Med (2021) 9(1):73. doi: 10.21037/atm-20-5404
    1. Petrelli F, Trevisan F, Cabiddu M, Sgroi G, Bruschieri L, Rausa E, et al. . Total Neoadjuvant Therapy in Rectal Cancer: A Systematic Review and Meta-Analysis of Treatment Outcomes. Ann Surg (2020) 271(3):440–8. doi: 10.1097/SLA.0000000000003471
    1. World Medical A. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA (2013) 310(20):2191–4. doi: 10.1001/jama.2013.281053
    1. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. . The Eighth Edition AJCC Cancer Staging Manual: Continuing to Build a Bridge From a Population-Based to a More “Personalized” Approach to Cancer Staging. CA Cancer J Clin (2017) 67(2):93–9. doi: 10.3322/caac.21388
    1. Chen R, Zheng RS, Zhang SW, Zeng HM, Wang SM, Sun KX, et al. . [Analysis of Incidence and Mortality of Esophageal Cancer in China, 2015]. Zhonghua Yu Fang Yi Xue Za Zhi (2019) 53(11):1094–7. doi: 10.3760/cma.j.issn.0253-9624.2019.11.004
    1. Kelly RJ, Ajani JA, Kuzdzal J, Zander T, Van Cutsem E, Piessen G, et al. . Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med (2021) 384(13):1191–203. doi: 10.1056/NEJMoa2032125
    1. Kesler KA, Helft PR, Werner EA, Jain NP, Brooks JA, DeWitt JM, et al. . A Retrospective Analysis of Locally Advanced Esophageal Cancer Patients Treated With Neoadjuvant Chemoradiation Therapy Followed by Surgery or Surgery Alone. Ann Thorac Surg (2005) 79(4):1116–21. doi: 10.1016/j.athoracsur.2004.08.042
    1. Kelly RJ, Zaidi AH, Smith MA, Omstead AN, Kosovec JE, Matsui D, et al. . The Dynamic and Transient Immune Microenvironment in Locally Advanced Esophageal Adenocarcinoma Post Chemoradiation. Ann Surg (2018) 268(6):992–9. doi: 10.1097/SLA.0000000000002410
    1. Kasi A, Abbasi S, Handa S, Al-Rajabi R, Saeed A, Baranda J, et al. . Total Neoadjuvant Therapy vs Standard Therapy in Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis. JAMA Netw Open (2020) 3(12):e2030097. doi: 10.1001/jamanetworkopen.2020.30097
    1. Cercek A, Roxburgh CSD, Strombom P, Smith JJ, Temple LKF, Nash GM, et al. . Adoption of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer. JAMA Oncol (2018) 4(6):e180071. doi: 10.1001/jamaoncol.2018.0071
    1. Ludmir EB, Palta M, Willett CG, Czito BG. Total Neoadjuvant Therapy for Rectal Cancer: An Emerging Option. Cancer (2017) 123(9):1497–506. doi: 10.1002/cncr.30600
    1. Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krleza-Jeric K, et al. . SPIRIT 2013 Statement: Defining Standard Protocol Items for Clinical Trials. Ann Intern Med (2013) 158(3):200–7. doi: 10.7326/0003-4819-158-3-201302050-00583

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren