A phase III ESCORT-NEO/NCCES01 study assessed the efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy versus chemotherapy alone in patients with locally advanced oesophageal squamous cell carcinoma. The findings demonstrate that the addition of camrelizumab to chemotherapy substantially enhances pathological complete response (pCR) rates in the intention-to-treat (ITT) population. Specifically, the pCR rate for the camrelizumab, albumin-bound paclitaxel and cisplatin group and the paclitaxel with cisplatin group was 28.0% versus 4.7%, while for camrelizumab, paclitaxel and cisplatin group and paclitaxel with cisplatin group was 15.4% versus 4.7%.
pCR outcomes exceed those of traditional neoadjuvant chemotherapy and are numerically comparable to neoadjuvant chemoradiotherapy’s for patients with locally advanced oesophageal squamous cell carcinoma in a meta-analysis. These results underscore the substantial potential of combining neoadjuvant immunotherapy with chemotherapy in the treatment of locally advanced oesophageal squamous cell carcinoma according to Drs. Jie He and Yin Li of the Section of Esophageal and Mediastinal Oncology, Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China and colleagues who published the findings on 2 July 2024 in the Nature Medicine.
The authors wrote in the background that recent phase III studies, along with a meta-analysis of randomised controlled trials, have not demonstrated a significant overall survival (OS) advantage when comparing neoadjuvant chemoradiotherapy to chemotherapy for patients with locally advanced oesophageal squamous cell carcinoma. Camrelizumab, a PD1 inhibitor, has demonstrated promising efficacy and safety in advanced oesophageal squamous cell carcinoma, including both chemotherapy-refractory and treatment-naïve cases, as evidenced by the ESCORT and ESCORT-1st studies.
Several phase Ib and II studies assessing neoadjuvant immunotherapy with camrelizumab and chemotherapy for locally advanced oesophageal squamous cell carcinoma report high pCR rates. Retrospective analysis suggests that neoadjuvant chemotherapy plus immunotherapy showed better 3-year OS rates and 3-year disease-free survival rates compared to neoadjuvant chemoradiotherapy. Despite these promising results, there remains a lack of phase III confirmatory studies to further validate these findings.
Refining the chemotherapy regimen is crucial for enhancing neoadjuvant treatment outcomes in oesophageal squamous cell carcinoma. Paclitaxel with cisplatin regimen is commonly used, but nab-paclitaxel has shown a superior therapeutic profile compared to traditional paclitaxel. Preference for nab-paclitaxel, especially when combined with immunotherapy in locally advanced oesophageal squamous cell carcinoma, is supported by several phase II studies. A retrospective analysis further substantiates this, revealing that neoadjuvant immunotherapy with nab-paclitaxel and cisplatin achieves higher pCR rates than the combination of immunotherapy and paclitaxel with cisplatin regimen.
The ESCORT-NEO/NCCES01 study, a multicentre, randomised, open-label phase III study aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic locally advanced oesophageal squamous cell carcinoma (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomised in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy.
Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin in 132 patients, camrelizumab, paclitaxel and cisplatin in 130 patients and paclitaxel with cisplatin in 129 patients, followed by surgical resection. Both the groups with camrelizumab received adjuvant camrelizumab. The dual primary endpoints were the pCR rate, as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators.
In the article published in the Nature Medicine, the authors report the final analysis of pCR rates. In the ITT population, the camrelizumab/nab-paclitaxel/cisplatin and camrelizumab/paclitaxel/cisplatin groups exhibited significantly higher pCR rates of 28.0% and 15.4% compared to 4.7% in the paclitaxel with cisplatin group (p < 0.0001 and p = 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature.
The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the camrelizumab/nab-paclitaxel/cisplatin group, 29.2% for the camrelizumab/paclitaxel/cisplatin group and 28.8% for the paclitaxel with cisplatin group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively.
Biomarker and patient-reported outcomes data are currently being collected as exploratory endpoints to enhance the understanding of treatment effects. This study demonstrates that neoadjuvant camrelizumab combined with chemotherapy significantly increased the pCR in the ITT population with a tolerable safety. This study contributes new evidence supporting neoadjuvant treatment in patients with locally advanced oesophageal squamous cell carcinoma and lays the foundation for developing and optimising future treatment strategies. The study investigators anticipate further confirmation of the findings as survival data continue to mature.
The study was funded by Jiangsu Hengrui Pharmaceuticals.
Reference
Qin J, Xue L, Hao A, et al. Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: the randomized phase 3 ESCORT-NEO/NCCES01 trial. Nature Medicine; Published online 2 July 2024. DOI: https://doi.org/10.1038/s41591-024-03064-w