Dataset Information

Long-term Efficacy of Neoadjuvant Chemoradiotherapy Plus Surgery for the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma: The NEOCRTEC5010 Randomized Clinical Trial.

ABSTRACT:

Importance

The prognosis of patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains poor after surgery. Neoadjuvant chemoradiotherapy (NCRT) has been shown to potentially improve survival.

Objective

To compare the treatment efficacy of NCRT plus surgery with surgery alone for long-term survival among patients with locally advanced ESCC.

Design, setting, and participants

The Neoadjuvant Chemoradiotherapy for Esophageal Cancer 5010 study was a multicenter open-label randomized phase 3 clinical trial that enrolled patients between June 1, 2007, and December 31, 2014. Follow-up ended on December 31, 2019. The study was conducted at 8 centers in China. A total of 451 patients aged 18 to 70 years with thoracic ESCC stage T1-4N1M0/T4N0M0 were enrolled and randomized. Data were analyzed from December 1, 2019, to June 30, 2020.

Interventions

Patients randomized to receive NCRT plus surgery (NCRT group) received preoperative chemotherapy (25 mg/m2 of vinorelbine on days 1 and 8 and 75 mg/m2 of cisplatin on day 1 or 25 mg/m2 of cisplatin on days 1 to 4) every 3 weeks for 2 cycles and concurrent radiotherapy (40.0 Gy, administered in 20 fractions of 2.0 Gy for 5 days per week) followed by surgery. Patients randomized to receive surgery alone (surgery group) underwent surgery after randomization.

Main outcomes and measures

The primary end point was overall survival in the intention-to-treat population. The secondary end point was disease-free survival.

Results

A total of 451 patients (mean [SD] age, 56.5 [7.0] years; 367 men [81.4%]) were randomized to the NCRT (n = 224) and surgery (n = 227) groups and were eligible for the intention-to-treat analysis. By December 31, 2019, 224 deaths had occurred. The median follow-up was 53.5 months (interquartile range, 18.2-87.4 months). Patients receiving NCRT plus surgery had prolonged overall survival compared with those receiving surgery alone (hazard ratio, 0.74; 95% CI, 0.57-0.97; P = .03), with a 5-year survival rate of 59.9% (95% CI, 52.9%-66.1%) vs 49.1% (95% CI, 42.3%-55.6%), respectively. Patients in the NCRT group compared with the surgery group also had prolonged disease-free survival (hazard ratio, 0.60; 95% CI, 0.45-0.80; P < .001), with a 5-year survival rate of 63.6% (95% CI, 56.0%-70.2%) vs 43.0% (95% CI, 36.0%-49.7%), respectively.

Conclusions and relevance

In this randomized clinical trial, treatment with NCRT plus surgery significantly improved long-term overall survival and disease-free survival and therefore may be considered a standard of care for patients with locally advanced ESCC.

Trial registration

ClinicalTrials.gov Identifier: NCT01216527.

SUBMITTER: Yang H

PROVIDER: S-EPMC8223138 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundProgrammed death 1 (PD-1) inhibitor demonstrated durable antitumor activity in advanced esophageal squamous cell carcinoma (ESCC), but the clinical benefit of perioperative immunotherapy in ESCC remains unclear. This study evaluated the efficacy and safety of neoadjuvant chemoradiotherapy (nCRT) combined with the PD-1 inhibitor toripalimab in patients with resectable ESCC.MethodsFrom July 2020 to July 2022, 21 patients with histopathologically confirmed thoracic ESCC and clinical staged as cT1-4aN1-2M0/cT3-4aN0M0 were enrolled. Eligible patients received radiotherapy (23 fractions of 1.8 Gy, 5 fractions a week) with concurrent chemotherapy of paclitaxel/cisplatin (paclitaxel 45 mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22, 29 and two cycles of toripalimab 240 mg every 3 weeks after nCRT for neoadjuvant therapy before surgery, four cycles of toripalimab 240 mg every 3 weeks for adjuvant therapy after surgery. The primary endpoint was the major pathological response (MPR) rate. The secondary endpoints were safety and survival outcomes.ResultsA total of 21 patients were included, of whom 20 patients underwent surgery, 1 patient refused surgery and another patient was confirmed adenocarcinoma after surgery. The MPR and pathological complete response (pCR) rates were 78.9% (15/19) and 47.4% (9/19) for surgery ESCC patients. 21 patients (100.0%) had any-grade treatment-related adverse events, with the most common being lymphopenia (100.0%), leukopenia (85.7%), neutropenia (52.4%). 14 patients (66.7%) had adverse events of grade 3 with the most common being lymphopenia (66.7%). The maximum standardized uptake value and total lesion glycolysis of positron emission tomography/CT after neoadjuvant therapy well predicted the pathological response. The peripheral CD4+%, CD3+HLA-DR+/CD3+%, CD8+HLA-DR+/CD8+%, and IL-6 were significant differences between pCR and non-pCR groups at different times during neoadjuvant therapy. Three patients had tumor relapse and patients with MPR have longer disease-free survival than non-MPR patients.ConclusionsnCRT combined with perioperative toripalimab is effective and safe for locally advanced resectable ESCC. Long-term survival outcomes remain to be determined.Trial registration numberNCT04437212.