The Sequence of Chemotherapy and Toripalimab Might Influence the Efficacy of Neoadjuvant Chemoimmunotherapy in Locally Advanced Esophageal Squamous Cell Cancer—A Phase II Study

Abstract

BackgroundThere is no standard neoadjuvant therapy for locally advanced esophageal cancer in China. The role of neoadjuvant chemotherapy plus immunotherapy for locally advanced esophageal cancer is still being explored.MethodsThis open-label, randomized phase II study was conducted at a single center between July 2019 and September 2020; 30 patients with locally advanced esophageal squamous cell carcinoma (ESCC) (T3, T4, or lymph-node positive) were enrolled. Patients were randomized according to the enrollment order at a 1:1 ratio to receive chemotherapy on day 1 and toripalimab on day 3 (experimental group) or chemotherapy and toripalimab on day 1 (control group). The chemotherapeutic regimen was paclitaxel and cisplatin. Surgery was performed 4 to 6 weeks after the second cycle of chemoimmunotherapy. The primary endpoint was pathological complete response (pCR) rate, and the secondary endpoint was safety and disease-free survival.ResultsThirty patients completed at least one cycle of chemoimmunotherapy; 11 in the experimental group and 13 in the control group received surgery. R0 resection was performed in all these 24 patients. Four patients (36%) in the experimental group and one (7%) in the control group achieved pCR. The experimental group showed a statistically non-significant higher pCR rate (p = 0.079). PD-L1 combined positive score (CPS) examination was performed in 14 patients; one in the control group had a PD-L1 CPS of 10, and pCR was achieved; the remaining 13 all had ≤1, and 11 of the 13 patients received surgery in which two (in the experimental group) achieved pCR. Two patients endured ≥grade 3 adverse events, and one suffered from grade 3 immune-related enteritis after one cycle of chemoimmunotherapy and dropped off the study. Another patient died from severe pulmonary infection and troponin elevation after surgery.ConclusionsAlthough the primary endpoint was not met, the initial results of this study showed that delaying toripalimab to day 3 in chemoimmunotherapy might achieve a higher pCR rate than that on the same day, and further large-sample clinical trials are needed to verify this.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT 03985670.

Pathologic Complete Response Prediction to Neoadjuvant Immunotherapy Combined with Chemotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: Real-World Evidence from Integrative Inflammatory and Nutritional Scores

“…Recently, more and more studies revealed that nICT is safe and feasible for patients with LA-ESCC. 8–10 The results demonstrated that nICT had manageable adverse effects, high R0 resection rate, promising pCR rate and limited postoperative complications.…”

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

“…Among the 27 studies, 8 trials with 221 patients examined nICRT ( 14 – 21 ), 19 trials with 588 patients examined nICT ( 22 – 40 ). Except one two-arms trial ( 33 ), all included studies were single-arm trials. Most of trials were conducted in China (20/27).…”

“…Most of trials were conducted in China (20/27). ICI was concurrently administered with CT or CRT in all studies except one trial ( 33 ). The most commonly CT regimen was paclitaxel plus carboplatin or cisplatin (PC/TP) (18/27).…”

“…There was only one two-arms trial ( 33 ) which was rated with a unclear risk of bias, others were single-arm trials. As single-arm trials have a high risk of bias by their nature, they were not further assessed for bias.…”

Systematic review and meta-analysis of endoscopic ultrasonography in staging diagnosis of esophageal cancer after neoadjuvant radiotherapy and chemotherapy

“…In terms of the structure of EUS, a miniature high-frequency ultrasonic probe is installed on the top of the endoscope, and an ultrasonic scan can be performed by the endoscope entering the body to obtain the ultrasonic images of the features of gastrointestinal tissue. The obtained images can be of some help to more intuitive and accurate diagnosis of disease and the implementation of follow-up targeted treatment plans (28,29). EUS can measure the diameter and cross-sectional area of the esophageal wall and the gastric wall by ultrasound.…”