Tislelizumab combined with chemotherapy as neoadjuvant therapy for surgically resectable esophageal cancer: A prospective, single-arm, phase II study (TD-NICE)

Yan, Xiaolong; Duan, Hongtao; Ni, Yicheng; Zhou, Yunyun; Wang, Xiaoping; Qi, Haini; Gong, L.; Liu, Honggang; Tian, Feng; Lu, Qiang; Sun, Jianguo; Yang, Ende; Zhong, Donglai; Wang, Tao; Huang, Lan; Wang, Jian; Wang, chaoyang; Wang, Yuanyong; Wan, Zhiguo; Lei, Jie; Zhao, Jinbo; Jiang, Tao

doi:10.1016/j.ijsu.2022.106680

Cited by 121 publications

(96 citation statements)

References 50 publications

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“…PD-L1 expression has been demonstrated to be a potential biomarker for ICI efficacy in metastatic EC, while its predictive value for tumor pathologic response in neoadjuvant immunotherapy setting is under evaluation. Two trials of nICT ( 34 , 37 ) showed that higher PD-L1 expression was associated higher rate of pCR in resectable EC. While, no predictive value of PD-L1 expression was observed in another two trials of nICT ( 30 , 35 ).…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant immune checkpoint inhibitor in combination with chemotherapy or chemoradiotherapy in resectable esophageal cancer: A systematic review and meta-analysis

Wang

Liu

et al. 2022

Front. Immunol.

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BackgroundNeoadjuvant immune checkpoint inhibitor in combination with chemotherapy (nICT) or chemoradiotherapy (nICRT) has been tested in resectable esophageal cancer. Nevertheless, efficacy and safety for this new strategy have not been clearly demonstrated.Patients and methodsPubMed, Embase, Cochrane Library, Web of Science, and scientific meetings were searched for eligible trials until June 30, 2022. The primary outcome of interest was pathological complete response (pCR). The random-effect model was used for statistical analysis.ResultsTwenty-seven trials with 809 patients were identified. The estimated rates of pCR for nICRT and nICT were comparable (32.7%, 95% CI: 20.3%-45.1% vs 26.3%, 95% CI: 19.8%-32.8%; P = 0.37). As for safety, surgical resection rate, R0 resection rate, surgical delay rate, and surgical mortality rate were similar between nICRT and nICT, while more grade ≥3 treatment-related adverse events were observed for nICRT (52.6%, 95% CI: 30.7%-74.5% vs 19.9%, 95% CI: 8.8%-31.0%; P = 0.01). In subgroup analysis, nICRT achieved higher pCR rate compared to nICT (56.2%, 95% CI: 41.0%-71.3% vs 27.2%, 95% CI: 20.2%-34.1%; P < 0.001) for squamous cell carcinoma (SCC) but adenocarcinoma. In patients receiving nICT, PD-L1 expression CPS ≥1 showed higher pCR rate compared to CPS <1 (51.3%, 95% CI: 41.4%-61.2% vs 26.6%, 95% CI: 8.6%-44.5%; P = 0.02); regimen of paclitaxel plus carboplatin/cisplatin (PC/TP) and 3-4 cycles of nICT did not lead to an significantly improved pCR rate compared to other chemotherapy regimens and 2 cycles of nICT, respectively, despite without increased toxicity.ConclusionBoth nICT and nICRT achieved promising pCR rates with acceptable tolerability, and nICRT was likely to have more antitumor efficacy compared to nICT for patients with SCC. PD-L1 status seemed to be predictive of pCR in patients receiving nICT; pCR rate did not appear to be greatly affected by CT regimen and increasing cycles of nICT.

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Section: Discussionmentioning

confidence: 99%

Neoadjuvant immune checkpoint inhibitor in combination with chemotherapy or chemoradiotherapy in resectable esophageal cancer: A systematic review and meta-analysis

Wang

Liu

et al. 2022

Front. Immunol.

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“…Postoperative complications occurred in 77.8% of the 36 patients. No treatment-related surgical delay or death occurred [48] …”

Section: Immune Checkpoint Therapy For Resectable Ecmentioning

confidence: 99%

“…A further multicenter study with a larger sample size (143 participants) and PCR set as the primary outcome measure, PALACE II (NCT04435197), is ongoing. [48] Sintilimab Sintilimab is another PD-1 inhibitor, which is approved by the FDA for the treatment of certain type of Hodgkin's lymphoma and non-small cell lung cancer (NSCLC). Sintilimab is mainly used for neoadjuvant treatment of ESCC.…”

Section: Pembrolizumabmentioning

confidence: 99%

Treatments for resectable esophageal cancer: from traditional systemic therapy to immunotherapy

Yan

Feng

et al. 2022

Chinese Medical Journal

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Esophageal cancer (EC) has a high incidence and poor prognosis. The two major histological types, squamous cell carcinoma and adenocarcinoma, differ in their epidemiology and treatment options. Patients with locally advanced EC benefit from multimodal therapy concepts including neoadjuvant chemotherapy, neoadjuvant chemoradiotherapy, and perioperative chemotherapy. Currently, immunotherapy for the solid tumor is a hot spot. Treatment with adjuvant immune checkpoint inhibitors (ICIs) is the first immunotherapy for resectable EC listed in the latest National Comprehensive Cancer Network Guidelines for the Esophageal and Esophagogastric Junction Cancers. Recent clinical trials have established ICIs for three treatment models of resectable EC. Their short-term results demonstrated ideal efficacy and tolerable toxicity, though some concerns remain. This review summarizes the novel data on the ICIs for resectable EC and lists the registered related clinical trials. Hopefully, this review can provide a reference for ongoing research on the treatment options for resectable EC.

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“…In addition, considering the recent clinical bene ts of paclitaxel in head and neck squamous cell carcinoma (HNSCC) and ESCC populations, it is tempting to speculate that paclitaxel can sensitize tumor cells to T cells and disturb immunosuppressive mechanisms and has a strong synergistic effect with PD-1/PD-L1 inhibitors. Therefore, in two prospective, single-arm, phase II clinical trials, TD-NICE [14] and KEYSTONE-001 [8] , researchers used PD-1 inhibitors in combination with paclitaxel and platinum in patients with resectable locally advanced ESCC. The results showed that the R0 resection rates were 97.2% and 100%, the MPR rates were 72% and 72.4%, and the pCR rates were 50% and 41.1%, respectively.…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab combined with paclitaxel and platinum as induction therapy for locally advanced esophageal squamous cell carcinoma: A retrospective, single-center, three-arm study

Lin

Huang

et al. 2022

Preprint

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Background Pembrolizumab has been approved by the Food and Drug Administration (FDA) for the first-line treatment of locally advanced or metastatic esophageal cancer. This study investigated the efficacy and safety of pembrolizumab combined with paclitaxel and platinum for the treatment of locally advanced and potentially resectable esophageal squamous cell carcinoma (ESCC). Methods In this retrospective, single-center, three-arm study, patients with locally advanced and potentially resectable ESCC received pembrolizumab (200 mg on day 1) in combination with paclitaxel (135 mg/m2 on day 1) and nedaplatin (100 mg/m2 on day 1) as induction therapy once every 3 weeks. After 4 cycles of systemic therapy in the first stage, patients who chose to undergo radical surgery were divided into group A, patients who underwent radical radiotherapy were divided into group B, and patients who did not undergo any radical therapy were divided into group C. Maintenance treatment with pembrolizumab was performed in all 3 groups. The efficacy and safety of pembrolizumab were evaluated through clinical data, such as the objective response rate (ORR), progression-free survival (PFS), and safety assessment. Results From August 2019 to June 2022, a total of 39 patients were included in this study. After immune response evaluation in the first stage, 34 (87.2%) patients achieved immune partial response (iPR), and 5 (12.8%) patients achieved immune stable disease (iSD). The ORR was 87.1% (27/31), and the disease control rate (DCR) was 100%. Twenty-two patients in group A underwent surgery, and all patients underwent R0 resection. The major pathological response (MPR) rate was 68.2% (15/22), and the pathological complete response (pCR) rate was 45.5% (10/22). Nine patients in group B chose radiotherapy as the radical therapeutic method after the tumors had shrunk significantly. Eight patients in group C did not undergo any radical therapy. All patients received maintenance treatment with pembrolizumab, and the median period of pembrolizumab therapy was 8 cycles (4–22 cycles). The median follow-up time was 16.6 months (6–34 months), and the median overall survival (OS) and PFS times were not reached in either groups A or B. The incidence of severe adverse events (AEs) (grade ≥ 3) was 15.4% (6/39), and the main treatment-related AEs were rash and hypothyroidism. One patient stopped treatment after 4 cycles of induction therapy due to a severe rash. There was no significant difference in the incidence of AEs between groups A and B. Conclusions Pembrolizumab in combination with paclitaxel and platinum as induction therapy for locally advanced and potentially resectable ESCC has a high ORR, high surgical conversion, MPR, pCR, and R0 resection rates, and tolerable AEs in the operation group. For patients unwilling to undergo surgical treatment, pembrolizumab could provide good benefits in sequential treatment with radical radiotherapy or maintenance therapy. This treatment model in different clinical scenarios is worth further exploration in the field of immunotherapy for locally advanced and potentially resectable ESCC.

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Tislelizumab combined with chemotherapy as neoadjuvant therapy for surgically resectable esophageal cancer: A prospective, single-arm, phase II study (TD-NICE)

Cited by 121 publications

References 50 publications

Neoadjuvant immune checkpoint inhibitor in combination with chemotherapy or chemoradiotherapy in resectable esophageal cancer: A systematic review and meta-analysis

Neoadjuvant immune checkpoint inhibitor in combination with chemotherapy or chemoradiotherapy in resectable esophageal cancer: A systematic review and meta-analysis

Treatments for resectable esophageal cancer: from traditional systemic therapy to immunotherapy

Pembrolizumab combined with paclitaxel and platinum as induction therapy for locally advanced esophageal squamous cell carcinoma: A retrospective, single-center, three-arm study

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