415 Toripalimab plus nab-paclitaxel and carboplatin as neoadjuvant therapy for patients with esophageal squamous cell carcinoma at clinical stage T2-T4/N0-N2/M0: a single-arm, single-center clinical study

Abstract

BackgroundSeveral immune checkpoint inhibitors (ICIs), represented by programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies, have been approved for treatment of various malignant tumors (including advanced esophageal cancer) worldwide, and previous studies confirmed that they can significantly improve overall survival.1 However, there has been limited research on the use of ICIs as neoadjuvant therapy for patients with esophageal cancer. Toripalimab is a humanized IgG4 monoclonal antibody that targets PD-1. The objective of this study is to evaluate the efficacy and safety of toripalimab plus chemotherapy as a neoadjuvant therapy regimen for treatment of patients with locally advanced esophageal squamous cell carcinoma (ESCC).MethodsThis single-arm, single-center study enrolled patients with ESCC at clinical stage T2-T4/N0-N2/M0, who were eligible for radical resection and regional lymph node dissection. The patients received 2–3 cycles of toripalimab (240 mg d1, Q3W) in combination with nab-paclitaxel (260 mg/m2 d1, Q3W) and carboplatin (AUC=5 d1, Q3W) before surgery. Preoperative evaluation was performed within 4 weeks after the last administration of chemotherapy. The primary endpoints were pathologic complete response (PCR) and major pathologic response (MPR), and the secondary endpoints were safety and feasibility of the neoadjuvant immunotherapy.ResultsSeventeen patients diagnosed with ESCC at a pre-treatment clinical stage of T2-T4/N0-N2/M0 were included. After neoadjuvant therapy, 15 of 17 patients (88.2%) experienced downstaging and met the surgical criteria. Twelve patients (80.0%) underwent surgery without delay and 3 patients (20.0%) refused surgery. The tumors were completely removed in all 12 patients (R0 resection rate: 100%). Seven patients (58.3%) achieved MPR and 2 (16.7%) achieved PCR. The median post-surgical follow-up time was 4.5 months, and there were no recurrences. Treatment-related adverse events (TRAEs) of the neoadjuvant therapy were tolerable. Grade 3 or higher TRAEs occurred in 2 patients (11.8%), but these did not delay surgery.ConclusionsToripalimab in combination with chemotherapy as neoadjuvant therapy showed promising anti-tumor activity with acceptable tolerance for locally advanced ESCC, as demonstrated by reducing the tumor burden, improving the R0 resection rate, reducing the postoperative recurrence rate, and no delays in surgery.AcknowledgementsN/AEthics ApprovalThis study was approved by the Ethics Board of the Army Medical center of the PLA, approval number 142(2018).ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.ReferenceWu X, Gu Z, Chen Y, et al. Application of PD-1 blockade in cancer immunotherapy. Comput Struct Biotechnol J 2019;17:661–674.

Neoadjuvant camrelizumab plus chemotherapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC‐ESCC2019): A multicenter, phase 2 study

“…This 2-week pattern might also be part of the reason for higher CPR rates compared to neoadjuvant therapy with toripalimab plus chemotherapy. 26,27 Multiple administration of low-dose chemotherapy strategies could repeatedly stimulate the release of tumor antigens, thereby enhancing the effect of immunotherapy. Therefore, the addition of radiotherapy or increasing the cycles of NIC may further improve the CPR rate, but may result in more and severe AEs.…”

Efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced esophageal cancer: A meta-analysis

“…The other common metric used to assess the safety of neoadjuvant immunotherapy in combination with chemotherapy is the rate of surgical delay; usually, the ratio of patients delayed in surgery due to adverse events caused by neoadjuvant immunotherapy to all patients expected to have surgery. Of the 21 studies included, only five mentioned ( 20 – 22 , 28 , 34 ) no surgical delays. In the study by Jun Liu et al.…”

“…To understand the possible correlation between the type of ICI and the outcome of neoadjuvant immunotherapy in combination with chemotherapy, we performed subgroup analysis. The 21 selected studies included two studies in which patients were treated with pembrolizumab ( 36 , 38 ), four studies in which patients were treated with sintilimab ( 27 , 32 , 33 , 37 ), four studies in which patients were treated with toripalimab ( 20 , 25 , 26 , 34 ), and nine studies in which patients were treated with Carlizumab ( 19 , 21 – 23 , 28 – 31 , 35 ).The potential correlation between ICI type and the efficacy and safety of neoadjuvant immunotherapy in combination with chemotherapy has not seen significant findings, implying that ICI type does not currently predominate in neoadjuvant immunotherapy ( Figure 12 ).…”

“…( 36 ). Five studies ( 20 , 29 , 32 , 36 , 37 ) had MPRs greater than 55%. In the KEYNOTE-181 trial of neoadjuvant chemotherapy, postoperative pathology in 18 evaluable patients revealed MPR in nine (50%) ( 16 ).…”

Conversion Surgery Following Immunochemotherapy in Initially Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma—A Real-World Multicenter Study (RICE-Retro)

“…In terms of the use of immunochemotherapy in the neoadjuvant setting, Li et al reported that ORR and pCR reached 100% and 56%, respectively, in PALACE-1 (28). Other phase II clinical trials adopting neoadjuvant immunochemotherapy reported that ORR ranged from 66.7% to 85% and pCR ranged from 16.7% to 45.4% (23,(28)(29)(30)(31)(32)(33)(34)(35)(36). Compared with these studies, the disease response rate reported by RICE-retro study appeared to be lower than most neoadjuvant immunochemotherapy studies.…”