Durvalumab and tremelimumab with definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma

Abstract

BACKGROUND:The current standard treatment for patients with inoperable, locally advanced esophageal squamous cell carcinoma (ESCC) is definitive concurrent chemoradiotherapy (CCRT). METHODS: Patients with locally advanced ESCC received 2 cycles of 5-fluorouracil, cisplatin, durvalumab, and tremelimumab every 3 weeks with concurrent radiation therapy (60.2 or 64.5 grays). After completing CCRT plus immunotherapy, patients received 2 cycles of consolidative durvalumab and tremelimumab followed by durvalumab monotherapy every 4 weeks for 2 years after enrollment. Their survival outcomes were compared with those from a propensity score-matched historical control group that had received CCRT alone. RESULTS: In total, 40 patients were enrolled and analyzed. The 24-month progression-free survival (PFS) and overall survival rates were 57.5% and 75%, respectively. Compared with the historical control group (n = 75), the study population had significantly longer PFS (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.28-0.97; P = .040) and overall survival (HR, 0.49; 95% CI, 0.25-0.98; P = .043). In the study population, patients who had PD-L1-positive tumors (n = 28) had significantly longer PFS (HR, 0.20; 95% CI, 0.07-0.54; P < .001) and overall survival (HR, 0.16; 95% CI, 0.05-0.56; P = .001) compared with those who had PD-L1-negative tumors (n = 11). However, there was no difference in survival outcomes according to PD-L1 status in the historical control group, indicating a strong interaction between PD-L1-positive status and survival outcomes in the treatment groups (PFS, P for interaction = .003; overall survival, P for interaction = .002). CONCLUSIONS: Durvalumab and tremelimumab with definitive CCRT had promising efficacy in patients with locally advanced ESCC. In addition, PD-L1 expression had strong predictive value in the study population.

Comprehensive Curative Effect of Targeting PD-1 or Traditional Single-Agent Chemotherapy in Second-Line Therapy for Terminal or Metastatic Esophageal Cancer: A Systematic Review and Meta-Analysis

“…Research on toripalimab continues [ 37 ]. Regarding PD-L1 inhibitors, durvalumab and tremelimumab (a CTLA-4 inhibitor) combined with concurrent chemoradiotherapy (CCRT) are effective in patients with locally terminal ESCC [ 38 ], while adebrelimab combined with chemotherapy has shown good efficacy and safety in the first-line treatment of patients with locally advanced or metastatic ESCC [ 39 ]. Treatment with PD-1/PD-L1 inhibitors has a good effect on EC.…”

Recent Advances in Combination of Immunotherapy and Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma

“…A recent phase II clinical trial evaluated the efficacy of durvalumab and tremelimumab in conjunction with definitive CRT (5-fluorouracil + cisplatin) in patients with unresectable locally advanced ESCC [ 34 ]. The results showed that the PFS and OS at 24 months were 57.5% and 75%, respectively.…”

Overcoming resistance to PD-1/PD-L1 inhibitors in esophageal cancer

“…The effective combination of PD-1/PD-L1 blockade with other type of ICIs is under exploration in several malignancies including EC. A latest research reported that additional application of durvalumab and tremelimumab after chemoradiotherapy significantly improved survival in patients with locally advanced ESCC, especially in those with PD-L1 positive tumors ( 52 ). Additionally, some studies have found the combination of anti-PD-1/PD-L1 inhibitors with some chemokine or cytokine blockades might bring new solutions to overcome drug resistance.…”