Observation Of Clinical Efficacy Of Toripalimab Based Combination Therapy As Second-line In Esophageal Squamous Cell Carcinoma

BackgroundEsophageal carcinoma（EC）is a common malignant tumor of digestive tract,with highly invasive clinical characteristics and poor prognosis.The current standard treatment plans are far from meeting the clinical needs.Therefore,it is of great significance for the patients with advanced Esophageal cancer to explore new treatment plans.Immune checkpoint inhibitors（ICIs）,as a new type of antitumor drugs,have shown good antitumor activity and controllable safety in the treatment of a variety of malignant tumors.Toripalimab is the first approved immune checkpoint inhibitor in China.This study collected and observed the efficacy and safety of toripalimab combined with chemotherapy and antiangiogenic drug anlotinib in the second-line treatment of advanced and metastatic esophageal squamous cell carcinoma.ObjectiveThis study gives an evaluation to the efficacy and safety of the treatment of Toripalimab in combination with chemotherapy or Anlotinib applied to advanced esophageal squamous cell carcinoma patients,who suffer the recurrence or the metastasis after failure of previous first-line therapy。And we explored the predictors of the efficacy of immune combination therapy in patients with esophageal squamous cell carcinoma.Methods1.Clinical data were retrospectively collected from 29 patients admitted to Luoyang Central Hospital with pathologically confirmed esophageal squamous cell carcinoma from March 2019 to December 2020,all of whom had relapsed after first-line chemotherapy and received Toripalimab in combination with single-agent irinotecan or docetaxel chemotherapy,and objective remission rate（ORR）,disease control rate（DCR）,progressionfree survival（PFS）,incidence of adverse events,and biomarkers associated with efficacy were counted.2.Clinical data were retrospectively collected from June 2019 to June 2021 from 35 patients admitted to Luoyang Central Hospital with pathologically confirmed esophageal squamous carcinoma who had relapsed after first-line treatment and were treated with Toripalimab in combination with anlotinib,and the objective remission rate（ORR）,disease control rate（DCR）,progression-free survival（PFS）,incidence of adverse events and biomarkers associated with efficacy were counted.Results1.The objective response rate（ORR）,the disease control rate（DCR）,and the median PFS（m PFS）of patients with advanced esophageal squamous carcinoma treated with Toripalimab in combination with single-agent chemotherapy as the second-line treatment,are respectively 34.5%,62.8% and 4.5 months.Univariate analysis showed statistically significant differences in the effects of liver metastases,NLR and ECOG scores on patients’ PFS（P < 0.05）;multivariate Cox regression analysis based on univariate analysis showed that the presence of liver metastases in patients was an independent risk factor for PFS（P =0.009）.Adverse effects were predominantly grade 1-2,with the most common grade 3-4adverse events being diarrhea（10.34%）,neutropenia（6.90%）,and anemia（6.90%）,and no treatment-related deaths has been seen.2.The ORR of patients with advanced esophageal squamous carcinoma treated with the second-line treatment,Toripalimab combined with Anlotinib was 34.28%,DCR was71.43%,and m PFS was 4.2 months.Univariate analysis showed that previous history of surgery,liver metastasis,NLR,ECOG,and CD4+/CD8+ T lymphocytes were relevant factors affecting PFS;multifactorial Cox regression analysis showed that liver metastasis（P=0.002）,ECOG score（P=0.006）,and NLR（P=0.014）were independent risk factors affecting PFS.Adverse effects were predominantly grade 1-2,and the most common events of grade 3-4 were hypertension（5.71%）and leukopenia（5.71%）,and no treatment-related deaths has been seen.Conclusions1.As a second-line treatment,Toripalimab combined with single-agent chemotherapy applied to treat the advanced esophageal squamous cancer receives a relatively considerable efficacy,with tolerable adverse effects.But we saw a poor prognosis for patients with combined liver metastases.2.The second-line treatment of advanced esophageal squamous carcinoma by Toripalimab in combination with Anlotinib has similar efficacy to combination chemotherapy,while the incidence of adverse effects is relatively milder,the overall safety is acceptable.PFS is shorter in patients who suffer liver metastases and whose ECOG scores are high.CD4/CD8+ T cells and NLR may be relevant indicators for efficacy prediction.