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

Moritz Müller; Florian Posch; Dominik Kiem; Dominik Barth; Lena Horvath; Michael Stotz; Renate Schaberl-Moser; Martin Pichler; Richard Greil; Philipp J Jost; Andreas Seeber; Arno Amann; Konstantin Schlick; Armin Gerger; Jakob M Riedl

doi:10.1177/17588359211039930

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

Ther Adv Med Oncol. 2021 Sep 30:13:17588359211039930. doi: 10.1177/17588359211039930. eCollection 2021.

Authors

Affiliations

¹ Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
² IIIrd Medical Department of Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectious Disease, Salzburg Cancer Research Institute, Paracelsus Medical University, Salzburg, Austria.
³ Department of Internal Medicine V: Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, Innsbruck, Austria.
⁴ Division of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz 8036, Austria.

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.

Keywords: best supportive care; oesophageal cancer; palliative treatment; real-world study; second line therapy.