Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: the randomized phase 3 ESCORT-NEO/NCCES01 trial

Abstract

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial 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 LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n = 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n = 130); and paclitaxel with cisplatin (TP group; n = 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1-32.0, P < 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7-18.1, 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 Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034 .

Fig. 1. CONSORT diagram.

A total of 411 patients were screened for this study, of whom 391 were successfully enrolled between April 28, 2021, and August 7, 2023.

Extended Data Fig. 1. Post hoc subgroup analysis of pCR between Cam+nab-TP group and TP group.

The central points on each bar represent the mean difference in pCR rates between the two groups, while the bars indicate the 95% CI. pCR, pathological complete response; ECOG PS, Eastern Cooperative Oncology Group performance status; TPS, tumor proportion score; CPS, combined positive score; CI, confidence interval.

Extended Data Fig. 2. Post hoc subgroup analysis of pCR between Cam+TP group and TP group.

The central points on each bar represent the mean difference in pCR rates between the two groups, while the bars indicate the 95% CI. pCR, pathological complete response; ECOG PS, Eastern Cooperative Oncology Group performance status; TPS, tumor proportion score; CPS, combined positive score; CI, confidence interval.

Extended Data Fig. 3. Depth of pathological regression in primary tumor.

(a) Cam+nab-TP group, (b) Cam+TP group and (c) TP group. RVT, residual viable tumor cells; IQR, interquartile range.