Benefit of second-line therapy for advanced esophageal squamous cell carcinoma: a tri-center propensity score analysis

Abstract

Background: The level of evidence for palliative second-line therapy in advanced esophageal squamous cell carcinoma (aESCC) is limited. This is the first study that reports efficacy data comparing second-line therapy + active symptom control (ASC) versus ASC alone in aESCC. Methods: We conducted a tri-center retrospective cohort study ( n = 166) including patients with aESCC who had experienced disease progression on palliative first-line therapy. A propensity score model using inverse probability of treatment weighting (IPTW) was implemented for comparative efficacy analysis of overall survival (OS) in patients with second-line + ASC ( n = 92, 55%) versus ASC alone ( n = 74, 45%). Results: The most frequent second-line regimens used were docetaxel (36%) and paclitaxel (18%). In unadjusted primary endpoint analysis, second-line + ASC was associated with significantly longer OS compared with ASC alone [hazard ratio (HR) = 0.49, 95% confidence interval (CI): 0.35–0.69, p < 0.0001]. However, patients in the second-line + ASC group were characterized by more favorable baseline features including a better Eastern Cooperative Oncology Group (ECOG) performance status, a longer first-line treatment duration and lower C-reactive protein levels. After rigorous adjusting for baseline confounders by re-weighting the data with the IPTW the favorable association between second-line and longer OS weakened but prevailed. The median OS was 6.1 months in the second-line + ASC group and 3.2 months in the ASC group, respectively (IPTW-adjusted HR = 0.40, 95% CI: 0.24–0.69, p = 0.001). Importantly, the benefit of second-line was consistent across several clinical subgroups, including patients with ECOG performance status ⩾1 and age ⩾65 years. The most common grade 3 or 4 adverse events associated with palliative second-line therapy were hematological toxicities. Conclusion: This real-world study supports the concept that systemic second-line therapy prolongs survival in patients with aESCC.

Multimodal radiotherapy in recurrent refractory metastatic esophageal cancer

“…Chemotherapy or chemotherapy plus immunotherapy represent alternative options for metastatic ESCC with positive PD-L1 expression [7] . The combined use of docetaxel and cisplatin has been found to have a response rate of 25-34.2% in metastatic esophageal carcinoma after failure of PF rst-line therapy [13][14][15][16] .…”

Comprehensive treatment obtained complete remission in recurrent refractory metastatic esophageal cancer

“…Chemotherapy or chemotherapy plus immunotherapy represent alternative options for metastatic ESCC with positive PD-L1 expression [7] . The combined use of docetaxel and cisplatin has been found to have a response rate of 25-34.2% in metastatic esophageal carcinoma after failure of PF rst-line therapy [13][14][15][16] . Sintilimab is reported to be superior to chemotherapy alone for the second-line treatment of metastatic esophageal squamous cell carcinoma [17,18] .…”

Potent molecular-targeted therapies for advanced esophageal squamous cell carcinoma

“…2,[130][131][132][133] A retrospective study using a propensity score model showed the clinical benefit of OS in a second-line therapy compared with active symptom control alone for patients with ESCC, with a hazard ratio (HR) of 0.40 [95% confidence interval (CI), 0.24-0.69]. 134…”