Multivariate prognostic index and triplet regimen efficacy predictive index in locally advanced and metastatic gastric cancer: pooled analysis from three clinical trials using individual patient data

Abstract

Background: To construct an effective prognostic index to predict overall survival (OS) and triplet regimen efficacy for advanced gastric cancer (AGC) patients treated with platinum-based and fluorouracil-based chemotherapy.

Objectives: Between 2011 and 2021, 679 patients from two randomized phase III trials and one phase II trial were enrolled.

Designs: We collected 11 baseline clinicopathological and 14 hematological parameters to establish a prognostic index.

Methods: Univariate and multivariate Cox analyses were used to screen prognostic factors, and a prognostic index nomogram was conducted.

Results: Seven prognostic factors were identified: primary tumor site in the non-proximal gastric area, signet-ring cell carcinoma (SRCC)/mucinous carcinoma, peritoneal metastasis, neutrophil count higher than the upper limit of normal value (ULN), lymphocyte count lower than the lower limit of normal value, lactate dehydrogenase level higher than the ULN, and alkaline phosphatase level higher than the ULN as significant for prognosis. A prognostic nomogram named the Fudan advanced gastric cancer prognostic risk score (FARS) index was constructed, and patients in the high-risk group had significantly shorter OS than those in the low-risk group (median OS, 15.5 versus 8.0 months, p < 0.001). The areas under the curve of the FARS index for 1-, 2-, and 3-year OS were 0.70, 0.72, and 0.77, respectively. A validation and external cohort verified the prognostic value of the FARS index. Moreover, three triplet regimen efficacy parameters were identified: SRCC/mucinous adenocarcinoma, primary tumor location in the non-proximal gastric area, and peripheral neutrophil count higher than the ULN; a TRIS index was subsequently conducted. In patients with any two of the three parameters, the triplet regimen showed significantly longer OS than the doublet regimen (p = 0.018).

Conclusion: The constructed FARS index to predict the OS of AGC patients and the TRIS index to screen out the dominant population for triplet regimens can be used to aid clinical decision-making and individual risk stratification.

Keywords: advanced gastric cancer; chemotherapy; overall survival; prognostic index; triplet regimen efficacy predictive index.

Figure 1.

(a) A risk score system of the seven risk factors using a nomogram. (b) The optimal cutoff value for the risk score was evaluated using the ‘Surv_cutpoint’. (c) In the training cohort, the Kaplan–Meier curve showed that patients in the high-risk group had significantly shorter OS than those in the low-risk group (p < 0.001). (d) The areas under the curve in the FARS index for 1-, 2-, and 3-year OS were 0.70, 0.72, and 0.77, respectively. (e) In the validation cohort, patients in the high-risk group had significantly shorter OS than those in the low-risk group (p < 0.001). (f) In the training cohort, the areas under the curve in the FARS index for 1-, 2-, and 3-year OS were 0.86, 0.89, and 0.84, respectively. (g) In the external cohort, patients in the high-risk group had significantly shorter OS than those in the low-risk group (p = 0.019). (h) In the external cohort, the areas under the curve in the FARS index for 1-, 2-, and 3-year OS were 0.71, 0.70, and 0.54, respectively. (i) In the exploration cohort, patients in the high-risk group had significantly shorter OS than those in the low-risk group (p < 0.001). (j) In the external cohort, the areas under the curve in the FARS index for 1-, 2-, and 3-year OS were 0.86, 0.79, and not available, respectively. FARS, Fudan Advanced Gastric Cancer Prognostic Risk Score; OS, overall survival.

Figure 2.

Forest plot of overall survival of patients with advanced gastric cancer in different subgroups of baseline clinicopathologic parameters in the training cohort.

Figure 3.

Forest plot of overall survival of patients with advanced gastric cancer in different subgroups of baseline hematological parameters in the training cohort.

Figure 4.

(a) In the patients with any two of the three parameters (159 patients), patients who received the triplet regimen had significantly longer OS than patients who received the doublet regimen p = 0.018). (b) In the patients with one parameter or without any parameter (500 patients), there was no statistical difference in OS between patients who received a triplet regimen and patients who received a doublet regimen (p = 0.799). OS, overall survival.