Neoadjuvant Sintilimab Plus Chemotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma

Abstract

BackgroundNeoadjuvant chemotherapy (nCT) and chemoradiotherapy (nCRT) are the standard treatments in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). Adding PD-1 inhibitor to the chemotherapy has shown significant clinical benefits in first-line treatment of advanced ESCC. This study evaluated the efficacy and safety of neoadjuvant sintilimab plus chemotherapy in patients with resectable locally advanced ESCC.MethodsThe clinical data of 96 patients with resectable locally advanced ESCC, treated with sintilimab plus chemotherapy followed by esophagectomy, were reviewed. The pathologic complete response (pCR) rate, major pathological response (MPR) rate, R0 resection rate, tumor downstaging, survival, and safety were retrospectively analyzed.ResultsPatients were between the ages of 43 and 78 years (interquartile range [IQR], 60–69 years). Forty (41.7%) were diagnosed with stage II ESCC, 52 (54.2%) with stage III, and 4 (4.2%) with stage IVA. Sixty-seven (69.8%) were male, and 84 (87.5%) patients had an ECOG PS of ≤1. Forty-eight (50.0%) patients received 3–4 cycles of the neoadjuvant treatment. Twenty-nine (30.2%) patients obtained pCR, and MPR was achieved in 60 (62.5%) patients. The R0 resection rate was 99%. Eighty (83.3%) patients achieved clinical downstaging, and 71 (74.0%) achieved pathological downstaging. The median follow-up was 8.9 months, and 1-year DFS rate was 95.2% (95% CI, 88.8%–100%). Grade 3–4 TRAEs occurred in 12 (12.5%) patients, and the incidence of grade 3–4 surgical complications was 2.1%. No deaths were reported.ConclusionThese real-world data revealed that neoadjuvant sintilimab plus chemotherapy could provide encouraging pCR with good tolerability for resectable locally advanced ESCC, and this regimen warrants further exploration in prospective clinical studies.

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

“…Twelve of the 21 studies achieved 100% R0 resection, with an overall mean R0 resection rate of 97.5%. The remaining nine studies ( 15 , 19 , 23 – 25 , 27 , 32 , 36 , 37 ) had individual ORs as well as combined ORs <1 (OR=0.95,95% CI: 0.90–1.00, p <0.001; Figure 5 ). Heterogeneity ( p <0.001, I 2 = 94%) was significant, so a random-effects model was used.…”

“…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 ).…”

“…In the end, 21 studies, which included 759 patients, were used for the analysis. Of the 21 studies included, there were 20 single-arm open-label cohort studies (15,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37) and there was one two-arm open-label randomized controlled trial (RCT) (38). Of the 21 studies included, three are still ongoing (26,29,30) and 18 (15, 19-25, 27, 28, 31-38) have been completed.…”

“…( 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 ).…”

“…As for the surgical resection rate, the combination of neoadjuvant immunotherapy with chemotherapy had a mean level of 86.6%. The incidence of surgical complications was mentioned in only three trials [47.1% ( 23 ) and 26.3% ( 24 ) and 51.0% ( 37 )]. No postoperative deaths were reported, and only two patients ( 23 ).…”