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James Birch-Ford1,2, Ben Crosby3, Grace Langford3
1Whiston Hospital, Mersey and West Lancashire Teaching Hospitals NHS Trust, Prescot L35 5DR, UK.
Abstract:
Background: Chemoimmunotherapy has improved survival compared with chemotherapy alone in phase III trials of advanced oesophago-gastric (OG) cancers; however, real-world UK data under National Institute for Health and Care Excellence (NICE) eligibility criteria remain limited. This study evaluated the effectiveness and safety of first-line pembrolizumab- or nivolumab-based chemoimmunotherapy in routine clinical practice. Methods: We conducted a retrospective, multi-centre cohort study of patients with unresectable or metastatic oesophageal, gastro-oesophageal junction, or gastric cancers treated with first-line chemoimmunotherapy at two UK tertiary centres between April 2021 and July 2024. Clinical, laboratory, radiological, and toxicity data were collected. Radiological outcomes were based on retrospective review of reports issued by consultant radiologists during routine clinical care. Overall survival (OS) and progression-free survival (PFS) were analysed using the Kaplan-Meier method, with exploratory analyses of prognostic factors. Results: Seventy-six patients were included (59.2% ≥ 65 years; 81.6% adenocarcinoma; 71.1% metastatic). At a median follow-up of 11 months, 46 deaths had occurred. Median OS was 16.0 months (95% CI: 11.0-20.9), and median PFS was 8.0 months (95% CI: 6.8-9.2). Disease control occurred in 80.3% of patients and was associated with improved OS compared with progressive disease (17.0 vs. 4.0 months; p < 0.001). Survival outcomes did not differ significantly by tumour site, histology, or immunotherapy agent. Immunotherapy-related adverse events occurred in 31 patients (40.8%), with grade ≥ 3 toxicities in 13.2% and two treatment-related deaths. Exploratory analyses suggested potential associations between survival and baseline lymphocyte count and neutrophil-lymphocyte ratio, although these did not reach statistical significance. Conclusions: In this real-world UK multi-centre cohort, first-line chemoimmunotherapy demonstrated survival outcomes comparable to pivotal clinical trials, with manageable toxicity. These findings support the use of chemoimmunotherapy in routine practice. Prospective collaborative studies incorporating robust biomarker evaluation are warranted to optimise patient selection and better define predictors of response and toxicity.
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