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Selected Publication:
Halbherr, M.
Treatment patterns in metastatic and locally advanced gastroesophageal cancer: a real-world single-center cohort study
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2023. pp. 83
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- Authors Med Uni Graz:
- Advisor:
- Gerger Armin
- Riedl Jakob
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- Abstract:
- Introduction Although immune checkpoint inhibition has been recently shown to improve the outcome in a subset of patients with advanced gastroesophageal adenocarcinoma, treatment options in this setting are still limited and the prognosis remains modest. We aimed to evaluate how treatment patterns in the palliative first-, second- and third-line treatment of gastroesophageal adenocarcinoma have changed over the last 15 years before the introduction of immunotherapy and whether these treatment changes translated into an improved outcome. Material and methods In this single-center retrospective cohort study we included 382 patients with locally advanced unresectable or metastatic esophageal, gastric or gastroesophageal junction cancer, who underwent palliative systemic treatment at the Department of Oncology at the Medical University of Graz between 2006 and 2020. Based on a cut-off date set on January 1, 2013, patients were assigned to two nearly equally sized treatment era groups: Cohort A (2006-2012) and Cohort B (2013-2020). Primary endpoint of this study was the overall survival from start of palliative first-line (OS1) therapy. Co-secondary endpoints were the progression-free survival of palliative first-line (PFS1) and the OS and PFS in palliative second- and third-line (OS2, OS3, PFS2, PFS3). Results Significant differences in terms of treatment patterns and intensity were observed between Cohort A (n=175, 45.8%) and Cohort B (n=207, 54.2%). Overall, patients in Cohort B were treated more intensely, which is underlined by a higher proportion of patients undergoing triplet therapies in the first-line setting (Cohort A 12.0% vs. Cohort B 23.7%, p=0.001), as well a higher proportion of patients who received subsequent second- (Cohort A 43.4% vs. Cohort B 53.6%, p=0.005), and third-line treatment (Cohort A 13.1% vs. Cohort B 25.1%, p=0.738). In terms of our primary endpoint analysis, only a non-significant improvement of OS1 from start of palliative first-line could be observed for Cohort B. The median OS1 was 8.0 months in Cohort A vs. 9.7 months in Cohort B. (logrank p=0.055). After multivariable adjusting for potential confounders in Cox regression analysis, the impact of treatment era on OS1 further weakened (Hazard ratio (HR): 0.9, 95% CI: 0.7-1.3, p=0.706). The only independent predictors of adverse OS1 were higher ECOG performance status (HR for ECOG 1 vs ECOG 0: 1.9, 95% CI: 1.4-2.5), lower age (HR per 10-year increase: HR 0.8, 95% CI: 0.7-1.0) and increased baseline CRP (HR per doubling of CRP: HR 0.6, 95% CI: 0.3-1.0). In terms of the secondary endpoint analysis, significantly superior OS2 (4.7 vs. 7.0 months, p=0.006) and OS3 (3.2 vs 5.0 months; p=0.031) were shown for Cohort B, whereas the PFS was highly similar between the study cohorts across all three therapy lines. Conclusion Although treatment patterns of palliative systematic therapy in advanced gastroesophageal adenocarcinoma have changed over the last 15 years, our study indicates that these treatment changes did not translate into a significant overall improvement of survival.