1.Exploratory Analysis of Patients With Gastric/Gastroesophageal Junction Adenocarcinoma With or Without Liver Metastasis From the Phase 3 RAINBOW Study
Takatsugu OGATA ; Yukiya NARITA ; Zev A. WAINBERG ; Eric Van CUTSEM ; Kensei YAMAGUCHI ; Yongzhe PIAO ; Yumin ZHAO ; Patrick M. PETERSON ; Sameera R. WIJAYAWARDANA ; Paolo ABADA ; Anindya CHATTERJEE ; Kei MURO
Journal of Gastric Cancer 2023;23(2):289-302
Purpose:
Liver metastasis (LM) is reported in approximately 40% of patients with advanced/ metastatic gastric/gastroesophageal junction adenocarcinoma (metastatic esophagogastric adenocarcinoma; mGEA) and is associated with a worse prognosis. This post-hoc analysis from the RAINBOW trial reported the efficacy, safety, and biomarker outcomes of ramucirumab and paclitaxel combination treatment (RAM+PAC) in patients with (LM+) and without (LM−) LM at baseline.
Materials and Methods:
Patients (n=665) were randomly assigned on a 1:1 basis to receive either RAM+PAC (LM+: 150, LM−: 180) or placebo and paclitaxel (PL+PAC) (LM+: 138, LM−: 197). The overall survival (OS) and progression-free survival (PFS) were evaluated using stratified Kaplan–Meier and Cox regression models. The correlation of dichotomized biomarkers (VEGF-C, D; VEGFR-1,2) with efficacy in the LM+ versus LM− subgroups was analyzed using the Cox regression model with reported interaction P-values.
Results:
The presence of LM was associated with earlier progression than those without LM, particularly in patients receiving PL+PAC (hazard ratio [HR], 1.68). RAM+PAC treatment improved OS and PFS irrespective of LM status but showed greater improvement in LM+ than that in LM− (OS HR, 0.71 [LM+] vs. 0.88 [LM−]; PFS HR, 0.47 [LM+] vs. 0.76 [LM−]).Treatment-emergent adverse events were similar between patients with and without LM. No predictive relationship was observed between biomarker levels (VEGF-C, D; VEGFR-1,2) and efficacy outcome (OS, PFS) (all interaction P-values >0.05).
Conclusions
RAM provided a significant benefit, irrespective of LM status; however, its effect was numerically stronger in patients with LM. Therefore, RAM+PAC is a clinically meaningful therapeutic option for patients with mGEA and LM.
2.Prognostic Factor Analysis of Overall Survival in Gastric Cancer from Two Phase III Studies of Second-line Ramucirumab (REGARD and RAINBOW) Using Pooled Patient Data.
Charles S FUCHS ; Kei MURO ; Jiri TOMASEK ; Eric VAN CUTSEM ; Jae Yong CHO ; Sang Cheul OH ; Howard SAFRAN ; György BODOKY ; Ian CHAU ; Yasuhiro SHIMADA ; Salah Eddin AL-BATRAN ; Rodolfo PASSALACQUA ; Atsushi OHTSU ; Michael EMIG ; David FERRY ; Kumari CHANDRAWANSA ; Yanzhi HSU ; Andreas SASHEGYI ; Astra M LIEPA ; Hansjochen WILKE
Journal of Gastric Cancer 2017;17(2):132-144
PURPOSE: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. MATERIALS AND METHODS: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. RESULTS: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64–0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. CONCLUSIONS: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.
Adenocarcinoma
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Alkaline Phosphatase
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Appetite
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Aspartate Aminotransferases
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Clinical Decision-Making
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Disease Progression
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Double-Blind Method
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Drug Therapy
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Esophagogastric Junction
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Factor Analysis, Statistical*
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Humans
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L-Lactate Dehydrogenase
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Lymphocytes
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Mass Screening
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Neoplasm Metastasis
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Neutrophils
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Prognosis
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Proportional Hazards Models
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Quality of Life
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Sodium
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Stomach Neoplasms*