A phase II clinical trial of toripalimab combined with neoadjuvant chemoradiotherapy in locally advanced esophageal squamous cell carcinoma (NEOCRTEC1901)

Chen, Rui; Liu, Qianwen; Li, Qiaoqiao; Zhu, Yuandong; Zhao, Lei; Liu, Shiliang; Chen, Baoqing; Liu, Mengzhong; Hu, Yonghong; Lin, Ting; Li, Jibin; Chen, Jian-Zhang; Lv, Yingxin; Fu, Jianhua; Xi, Mian; Yang, Hong

doi:10.1016/j.eclinm.2023.102118

Cited by 18 publications

(6 citation statements)

References 36 publications

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“…The MPR and pCR rates in our study were higher than that reported in some previous nCRT studies (69.1% and 33.3% in FFCD 9901, 21 61% and 29% in CROSS, 14 63.4% and 27.7% in CMISG1701, 22 43.2% pCR in NEOCRTEC 5010 20 ) and the combination of chemotherapy and immunotherapy (68.6% and 39.2% in NICE, 10 58.8% and 31.4% in NIC-ESCC2019, 9 50% and 25% in GASTO1056, 11 50% and 20% in KEEP-G03. 23 Combining our results with the PALACE1 7 and NEOCRTEC 1901 17 studies, it appears that nCRT combined with immunotherapy has a superior pathological response. This could be attributed to the synergistic effect of CRT and immunotherapy, whereby the release of tumor neoantigens induced by CRT enhances adaptive immunity.…”

Section: Open Accesssupporting

confidence: 54%

Neoadjuvant chemoradiotherapy combined with sequential perioperative toripalimab in locally advanced esophageal squamous cell cancer

Xu,

Sun,

Liu

et al. 2024

J Immunother Cancer

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BackgroundProgrammed death 1 (PD-1) inhibitor demonstrated durable antitumor activity in advanced esophageal squamous cell carcinoma (ESCC), but the clinical benefit of perioperative immunotherapy in ESCC remains unclear. This study evaluated the efficacy and safety of neoadjuvant chemoradiotherapy (nCRT) combined with the PD-1 inhibitor toripalimab in patients with resectable ESCC.MethodsFrom July 2020 to July 2022, 21 patients with histopathologically confirmed thoracic ESCC and clinical staged as cT1-4aN1-2M0/cT3-4aN0M0 were enrolled. Eligible patients received radiotherapy (23 fractions of 1.8 Gy, 5 fractions a week) with concurrent chemotherapy of paclitaxel/cisplatin (paclitaxel 45 mg/m2and cisplatin 25 mg/m2) on days 1, 8, 15, 22, 29 and two cycles of toripalimab 240 mg every 3 weeks after nCRT for neoadjuvant therapy before surgery, four cycles of toripalimab 240 mg every 3 weeks for adjuvant therapy after surgery. The primary endpoint was the major pathological response (MPR) rate. The secondary endpoints were safety and survival outcomes.ResultsA total of 21 patients were included, of whom 20 patients underwent surgery, 1 patient refused surgery and another patient was confirmed adenocarcinoma after surgery. The MPR and pathological complete response (pCR) rates were 78.9% (15/19) and 47.4% (9/19) for surgery ESCC patients. 21 patients (100.0%) had any-grade treatment-related adverse events, with the most common being lymphopenia (100.0%), leukopenia (85.7%), neutropenia (52.4%). 14 patients (66.7%) had adverse events of grade 3 with the most common being lymphopenia (66.7%). The maximum standardized uptake value and total lesion glycolysis of positron emission tomography/CT after neoadjuvant therapy well predicted the pathological response. The peripheral CD4+%, CD3+HLA-DR+/CD3+%, CD8+HLA-DR+/CD8+%, and IL-6 were significant differences between pCR and non-pCR groups at different times during neoadjuvant therapy. Three patients had tumor relapse and patients with MPR have longer disease-free survival than non-MPR patients.ConclusionsnCRT combined with perioperative toripalimab is effective and safe for locally advanced resectable ESCC. Long-term survival outcomes remain to be determined.Trial registration numberNCT04437212.

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Section: Open Accesssupporting

confidence: 54%

Neoadjuvant chemoradiotherapy combined with sequential perioperative toripalimab in locally advanced esophageal squamous cell cancer

Xu,

Sun,

Liu

et al. 2024

J Immunother Cancer

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“…21 NEOCRTEC1901 trial showed nCRT combined with ICB treatment markedly reduced the residual tumor in lymph nodes. 7 Third, the data in this study need to be veri ed by a larger cohort.…”

Section: Discussionmentioning

confidence: 95%

“…6 NEOCRTEC1901 trial revealed that neoadjuvant PD-1 blockade (toripalimab) combined with concurrent chemoradiotherapy followed by surgery in resectable locally advanced ESCC helped to improve pCR rate up to 50%. 7 The e cacy of immunotherapy largely depends on the tumor microenvironment (TME). Numerous studies have shown that the in ltration of immune cells, such as T lymphocytes and macrophages, is directly related to patient's response to anti-tumor immunity and immune checkpoint blockade (ICB).…”

Section: Introductionmentioning

confidence: 99%

Immune cell patterns before and after neoadjuvant immune checkpoint blockade combined with chemoradiotherapy in locally advanced esophageal squamous cell carcinoma

Zheng,

Li,

Yuan

et al. 2024

Preprint

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Background: Neoadjuvant immune checkpoint blockade (ICB) combined with chemoradiotherapy offers high pathologic complete response (pCR) rate for patients with locally advanced esophageal squamous cell carcinomas (ESCC). But the dynamic tumor immune microenvironment modulated by such neoadjuvant therapy remains unclear. Patients and methods: A total of 41 patients with locally advanced ESCC were recruited. Paired matched pre- and post-treatment tissues were obtained for fluorescent multiplex immunohistochemistry (mIHC) and IHC analyses. The densities and spatial distributions of immune cells were determined by HALO modules. Results: The differences of immune cell patterns before and after treatment were investigated, using matched paired tissues of 41 patients who received R0 resection. In the pretreatment tissues, more stromal CD3+FoxP3+ Tregs and CD86+/CD163+ macrophages were observed in patients with residual tumor existed in the resected lymph nodes (pN1), compared with pCR patients. Spatial analyses showed majority of macrophages were mainly distributed in close proximity to tumor nest in pN1 patients. In the posttreatment tissues, pCR patients had less CD86+ cells infiltration, whereas higher CD86+ cell densities were significantly associated with higher tumor regression grades (TRG) in non-pCR patients. When comparing the paired pre- and post-treatment samples, heterogeneous tumor-associated immune cell patterns were found. Upon to the treatment, CD3+ T lymphocytes were slightly increased in pCR patients, but markedly decreased in non-pCRs. In contrast, a noticeable increase and a less obvious decrease of CD86+ cell infiltration was depicted in non-pCRs and pCRs, respectively. Furthermore, opposite trends of the treatment-induced alterations of CD8+ and CD15+ cells were observed between pN0 and pN1 patients. Conclusions: Collectively, our data demonstrate a comprehensive picture of tumor immune landscape before and after neoadjuvant ICB combined with chemoradiotherapy, and therefore provide rationale for the further improvement of neoadjuvant therapy in ESCC.

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“…As for the surgical aspect, several single-arm clinical trials have reported R0 resection rates after neoadjuvant nCT+ICIs ranging from 84.6% to 92.11% ( 22 , 23 ), and after nCRT+ICIs ranging from 98% to 100% ( 15 , 24 ). Similarly, in our study, both in the nCT+ICIs and nCRT+ICIs cohorts, the R0 resection rate reached 100%.…”

Section: Discussionmentioning

confidence: 99%

Comparison of neoadjuvant chemotherapy or chemoradiotherapy plus immunotherapy for locally resectable esophageal squamous cell carcinoma

Yang,

Yue,

Zhang

et al. 2024

Front. Immunol.

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BackgroundNeoadjuvant chemotherapy plus immunotherapy (nCT + ICIs) and neoadjuvant chemoradiotherapy plus immunotherapy (nCRT + ICIs) both induced favorable pathological response and tolerant toxicities for locally resectable esophageal squamous cell carcinoma (ESCC). However, few studies compared safety and efficacy between the two treatment strategies.MethodsThis retrospective study collected clinical data of locally resectable ESCC patients who underwent nCT + ICIs or nCRT + ICIs followed by esophagectomy from November 2019 to December 2022. The incidence of adverse events, surgical outcomes, short and long-term efficacy, and treatment costs were compared.ResultsA total of 206 patients were included, with a ratio of 158:48 between nCT + ICIs group and nCRT + ICIs group. The two groups exhibited well-balanced baseline characteristics. Most adverse events were grade 1-2 in both groups. The nCT + ICIs group had a longer operative time (334.00 ± 170.2 min vs 279.60 ± 88.31 min, P=0.020) than nCRT + ICIs group, but there were no differences in surgical complications. Although nCT + ICIs group had a lower pCR rate (32.3% vs 52.1%, P=0.004), the 2-year overall survival (84.42% vs 81.70%, P=0.860), 2-year disease-free survival (83.21% vs 80.47%, P=0.839), and recurrence patterns were similar to nCRT + ICIs group. In addition, nCT + ICIs group had significantly lower expenses (188796.00 ± 107704.00 RMB vs 231808.00 ± 48067.00 RMB, P=0.045).ConclusionOverall, nCT + ICIs have comparable safety and efficacy compared to nCRT + ICIs for locally resectable ESCC, but with lower hospitalization costs.

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A phase II clinical trial of toripalimab combined with neoadjuvant chemoradiotherapy in locally advanced esophageal squamous cell carcinoma (NEOCRTEC1901)

Cited by 18 publications

References 36 publications

Neoadjuvant chemoradiotherapy combined with sequential perioperative toripalimab in locally advanced esophageal squamous cell cancer

Neoadjuvant chemoradiotherapy combined with sequential perioperative toripalimab in locally advanced esophageal squamous cell cancer

Immune cell patterns before and after neoadjuvant immune checkpoint blockade combined with chemoradiotherapy in locally advanced esophageal squamous cell carcinoma

Comparison of neoadjuvant chemotherapy or chemoradiotherapy plus immunotherapy for locally resectable esophageal squamous cell carcinoma

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