Patient and caregiver socioeconomic burden of first-line systemic therapy for advanced gastroesophageal adenocarcinoma

Aim: This study assessed the work productivity and financial impact of advanced gastroesophageal adenocarcinomas, comprising gastric, esophageal and gastroesophageal junction cancers, on patients of working age and their caregivers. Patients & methods: A multicenter medical chart review and surveys of patients with advanced gastroesophageal adenocarcinoma and their caregivers was conducted in France, Germany, the UK, China, Japan and the USA. Results: Across differing regions, the study highlighted the impact of cancer on patients’ ability to work, to function normally and on their wellbeing, as well as the economic burden placed on patients and their caregivers. Conclusion: Advanced gastroesophageal adenocarcinomas have a significant impact on patients’ and caregivers’ well-being and are associated with reduced work productivity, and income loss.

Tumor Inflammation, Obesity, and Proliferative Status as Biomarkers in Gastroesophageal Adenocarcinoma

Recent epidemiological studies have shown that obesity, typically measured by increased body mass index (BMI), is associated with an increased risk of gastroesophageal adenocarcinoma (GEAC), but the contributing molecular and immune mechanisms remain unknown. Since obesity is known to promote chronic inflammation, we hypothesized that obesity leads to inflammation-related immune dysfunction, which can be reversed by immune-modulating therapy. To test our hypothesis, we examined the clinical and molecular data from advanced GEAC patients. To this end, 46 GEAC tumors were evaluated for biomarkers representing tumor inflammation, cell proliferation, and PD-L1 expression. A CoxPH regression model with potential co-variates, followed by pairwise post hoc analysis, revealed that inflammation in the GEAC tumor microenvironment is associated with improved overall survival, regardless of BMI. We also observed a significant association between cell proliferation and progression-free survival in overweight individuals who received immune-modulating therapy. In conclusion, our data confirm the role of the immune system in the natural course of GEAC and its responses to immunotherapies, but do not support the role of BMI as an independent clinically relevant biomarker in this group of patients.

P-OGC24 Comparison of the histopathological regression after neoadjuvant FLOT versus ECX in resectable gastroesophageal adenocarcinoma

Background Neoadjuvant chemotherapy is a key component in the treatment of resectable oesophagogastric cancer (OGC). Histopathological tumour regression is associated with a prognostic benefit in OGC. There is increased usage of the FLOT regimen as part of neoadjuvant chemotherapy (NAC) for these tumours. The initial phase 2 trial demonstrated complete pathological response (pCR) in 15% for FLOT versus 6% for ECX but there is no data outside a trial setting. The aim of this study was to evaluate the differences in pCR and the extent of downstaging between patients receiving FLOT versus ECX in the neoadjuvant setting. Methods Consecutive patients treated for OGC in a single, high-volume UK centre between 2018 and 2021 were identified from a contemporaneously maintained database. Patients underwent 3 cycles of ECX or 4 cycles of FLOT as part of NAC. Histopathological tumour regression was assessed by the Mandard classification. A comparison of T- and N stage migration between FLOT and ECX was performed. Major pCR was defined as TRG 1-2 based on the Mandard classification. Results The study included 162 patients. 6/84 (7.1%) patients receiving ECX and 5/78 (6.4%) patients receiving FLOT achieved a pCR (p = 0.853). 11/84 (13.1%) patients in the ECX group and 12/78 (15.4%) patients in the FLOT group achieved a major pCR (p = 0.677). With regards to stage migration by T-stage, 36 (42.9%) patients were downstaged and 6 patients (7.1%) were upstaged with ECX. Amongst FLOT patients, 42 (53.8%) were downstaged and 8 (10.3%) upstaged (p = 0.189). When comparing N-stage, 29 (34.5%) patients achieved downstaging and 28 (33.3%) were upstaged with ECX. 30 (38.5%) patients were downstaged and 20 (25.6%) were upstaged with FLOT (0.563). Conclusions There was no significant difference in pCR and stage migration rates between patients receiving neoadjuvant ECX and FLOT. pCR rates were lower than previously reported, and it is unclear if the difference in prognosis will translate comparable outcomes between patients receiving ECX versus FLOT.

Beyond Front-Line Therapy for Unresectable Gastroesophageal Adenocarcinoma: Are There Differences in Subsequent Therapy Sequencing?

Background: Platinum + fluoropyrimidine is standard front-line therapy for unresectable gastroesophageal adenocarcinoma (GA). Subsequent therapy recommendations are ramucirumab + paclitaxel (RAM/PAC), taxane, irinotecan, or trifluridine-tipiracil. RAM/PAC is the preferred 2nd line choice; however, patients can have a contraindication due to cumulative neuropathy. Our study assessed varied sequencing of second-line and third-line therapies comparing RAM/PAC followed by fluoropyrimidine + irinotecan (FOLFIRI/CAPEIRI) vs the opposite sequence. Methods: We retrospectively analyzed metastatic GA patients who received at least 3 lines of therapy. Two cohorts were studied. Group A: RAM/PAC second-line with FOLFIRI/CAPIRI third-line or Group B: FOLFIRI/CAPEIRI second-line followed by RAM/PAC. Primary outcome was overall survival (OS). Results: 94 patients were available for analysis (51 pts Group A: 43 pts Group B). No difference was observed in median OS from the start of second-line therapy (Group A =10.5 months vs. Group B = 11.1 months, p=0.97) or median OS from metastatic disease diagnosis (Group A = 19.8 months vs Group B = 19.4 months, p=0.73). Conclusions: Our study, examining a practical issue of how to sequence 2nd and 3rd line therapies, documents that one sequence versus the other does not compromise patient outcomes and overall our patients had an outstanding OS of beyond 19 months when they receive 3rd line therapy.