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.
摘要
背景.研究一致表明二线治疗的生存获益大于最佳支持治疗；但鲜有证据表明进一步增加治疗线数可改善晚期胃癌（AGC）患者的预后。
材料与方法.本研究从含868例AGC患者的真实世界队列开始回顾性分析接受至少三线治疗患者的基线参数、肿瘤特征和治疗数据。通过交叉表和卡方检验描述分类特征。研究通过单因素和多因素Cox回归模型探索既往线数的治疗强度和无进展生存期（PFS）对三线治疗的PFS和总生存期影响, 并通过对数秩检验Kaplan‐Meier估计曲线描述。
结果.共分析300例患者。最常见的原发性肿瘤部位为胃体部, 肠组织型占45.3%, 人表皮生长因子受体2阳性占14%。在三线治疗中, 45.7%患者接受单药化疗, 49.7%采用联合给药方案。一线治疗PFS≥6.9个月的患者预后要好于PFS较短的患者。相应地, 二线治疗PFS≥3.5个月对预后有积极影响。接受三线联合给药方案的患者预后要好于单药化疗患者。
结论.此项真实世界研究证实经选的AGC患者可接受三线治疗。既往治疗线数的较长PFS或强度更大的三线治疗对预后有积极影响。但需进一步定义最佳治疗顺序并确定适合二线以上治疗的候选者。
对临床实践的提示：晚期胃癌患者能否从三线治疗中获益还存在争议。本研究描述意大利临床实践的真实情景, 证实有相当比例的患者接受三线治疗。既往治疗线数的较长PFS或强度更大的三线治疗对预后有积极影响。研究通过纳入大量的真实世界患者提供日常临床实践的三线治疗信息；而且, 其结果有助于定义最佳治疗顺序并为选择适合二线以上治疗的候选者提供一些线索
Keywords: Advanced gastric cancer; Overall survival; Prognostic factors; Progression‐free survival; Third‐line chemotherapy.
© AlphaMed Press 2017.