Neoadjuvant Anlotinib and chemotherapy followed by minimally invasive esophagectomy in patients with locally advanced esophageal squamous cell carcinoma: Short-term results of an open-label, randomized, phase II trial

Abstract

BackgroundClinical benefits of neoadjuvant Anlotinib for locally advanced esophageal squamous cell carcinoma (ESCC) remains unclear. This study evaluated the efficacy and safety of neoadjuvant Anlotinib plus chemotherapy followed by minimally invasive esophagectomy (MIE) for the treatment of patients with locally advanced ESCC.MethodsPatients with locally advanced ESCC were randomly assigned to neoadjuvant Anlotinib combined with chemotherapy (Anlotinib group) or neoadjuvant chemoradiotherapy alone (nCRT group) with an allocation ratio of 1:1. The primary endpoint was the R0 surgical resection rate. Secondary endpoints included postoperative pathologic stage, complete response (CR) rate, and safety. Safety was assessed by adverse events (AEs) and postoperative complications.ResultsFrom August 2019 to August 2021, 93 patients were assigned to the nCRT or Anlotinib group. Of the 93 patients, 79 underwent MIE and were finally included in the per-protocol set (nCRT group: n=39; Anlotinib group: n=40). The R0 resection rate was 97.4% for nCRT versus 100.0% for Anlotinib group (p>0.05). Compared with the nCRT group, patients in the Anlotinib group had shorter total operation duration (262.2 ± 39.0 vs. 200.7 ± 25.5 min, p=0.010) and less blood loss (161.3 ± 126.7 vs. 52.4 ± 39.3 mL, p<0.001). No significant differences were found in the postoperative pathologic stage between the Anlotinib group and nCRT group (all p>0.05). Besides, the incidences of AEs (80.0% vs. 92.3%) and postoperative complications (22.5% vs. 30.8%) were similar between the two groups (all p>0.05).ConclusionsNeoadjuvant Anlotinib plus chemotherapy had a similar safety profile and pathologic response, but better surgical outcomes than nCRT for locally advanced ESCC.

A prospective single‐center, single‐arm, open‐label, phase II study of sintilimab and anlotinib combined with chemotherapy in neoadjuvant treatment of resectable esophageal cancer

“… 13 However, in a phase II clinical study, there was only a slight decrease in postoperative complications after anlotinib combined with chemotherapy compared to concurrent chemoradiotherapy, with incidences of 7.5% and 12.8%, respectively. 11 However, the incidence of anastomotic leakage was comparable between the two groups in this study. Therefore, no direct evidence indicates that this specific treatment directly increases the incidence of postoperative complications in patients.…”

“…Furthermore, the use of next‐generation sequencing (NGS) in this study suggested that anlotinib induces changes in the tumor immune microenvironment, improving the treatment efficacy and implying that antiangiogenesis might enhance the effect of immunotherapy when used in combination by modulating the tumor immune microenvironment 10 . Furthermore, in a study focusing on neoadjuvant treatment for resectable esophageal cancer, the addition of anlotinib and chemotherapy did not significantly differ in achieving pCR when compared to neoadjuvant concurrent chemoradiotherapy (10% vs. 7.7%) 11 . However, the incidence of adverse events (AEs) was lower in the anlotinib group than in the concurrent chemoradiotherapy group.…”

“…The incidence of anastomotic stoma was twice as high in the combination group compared to the control group (24% vs. 12%), suggesting that antiangiogenesis could contribute to the higher incidence of anastomotic leakage 13 . However, in a phase II clinical study, there was only a slight decrease in postoperative complications after anlotinib combined with chemotherapy compared to concurrent chemoradiotherapy, with incidences of 7.5% and 12.8%, respectively 11 . However, the incidence of anastomotic leakage was comparable between the two groups in this study.…”

“… 10 Furthermore, in a study focusing on neoadjuvant treatment for resectable esophageal cancer, the addition of anlotinib and chemotherapy did not significantly differ in achieving pCR when compared to neoadjuvant concurrent chemoradiotherapy (10% vs. 7.7%). 11 However, the incidence of adverse events (AEs) was lower in the anlotinib group than in the concurrent chemoradiotherapy group. Given the potential for combined antiangiogenic treatment regimens to revolutionize esophageal cancer treatment, a single‐center, open‐label, single‐arm study was conducted to investigate the efficacy of sintilimab and anlotinib combined with chemotherapy in the treatment of resectable esophageal cancer.…”

Pathologic complete response in patients with esophageal cancer receiving neoadjuvant chemotherapy or chemoradiation: A systematic review and meta‐analysis

“…The full‐text publications for the remaining 191 studies were reviewed. Of these, 84 studies 7,26–108 met the inclusion and exclusion criteria and were included in this systematic review and meta‐analysis, yielding a total of 6451 patients who received neoadjuvant therapy and had tumor response measured pathologically after surgery. Of the 84 included trials, 13 (15%) were published between 1992 and 2001, 31 (37%) between 2002 and 2011, and 41 (49%) between 2012 and 2022.…”