Outcomes of Advanced Gastric Cancer Patients Treated with at Least Three Lines of Systemic Chemotherapy

Abstract

Background Second‐line therapy has consistently demonstrated survival benefit if compared with best supportive care; however, there is limited evidence whether further lines of treatment may improve the prognosis of advanced gastric cancer (AGC) patients. Materials and Methods Starting from a real‐world cohort of 868 AGC patients, we retrospectively analyzed baseline parameters, tumor characteristics, and treatment data of those treated with at least three lines. Categorical features were described through cross‐tables and chi‐square test. We explored the impact of treatment intensity and progression‐free survival (PFS) experienced in previous lines on PFS and overall survival in third‐line by uni‐ and multivariate Cox regression models and described by Kaplan‐Meier estimator plot with log‐rank test. Results Overall, 300 patients were included in the analysis. The most common site of primary tumor was gastric body; 45.3% of cancers had an intestinal histotype, 14% were human epidermal growth receptor 2 positive. In third‐line, 45.7% of patients received a single‐agent chemotherapy, 49.7% a combination regimen. Patients who had experienced a first‐line PFS ≥6.9 months had a better prognosis compared with those who had achieved a shorter one. Consistently, a second‐line PFS ≥3.5 months positively influenced the prognosis. Patients receiving a third‐line combination regimen had better outcomes compared with those treated with a single‐agent chemotherapy. Conclusion Our real‐world study confirms that selected AGC patients may receive third‐line treatment. Longer PFS in previous lines or a more intense third‐line treatment positively influenced prognosis. Further efforts are warranted to define the best therapeutic sequences, and to identify the optimal candidate for treatment beyond second‐line. Implications for Practice The benefit of third‐line treatment to advanced gastric cancer patients is controversial. This study depicts a real scenario of the clinical practice in Italy, confirming that a non‐negligible proportion of patients receive a third‐line therapy. Longer progression‐free survival in previous treatment lines or higher third‐line treatment intensity positively influenced prognosis. Including a large number of real‐world patients, this study provides information on third‐line treatment from the daily clinical practice; moreover, its results help in defining the best therapeutic sequence and offer some hints to select the optimal candidate for treatment beyond second‐line.

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