Exploration of predictors of benefit from nivolumab monotherapy for patients with pretreated advanced gastric and gastroesophageal junction cancer: post hoc subanalysis from the ATTRACTION-2 study

Abstract

Background The phase 3 ATTRACTION-2 study demonstrated that nivolumab monotherapy was superior to placebo for patients with pretreated advanced gastric or gastroesophageal junction cancer, but early progression of tumors in some patients was of concern. Methods This post hoc analysis statistically explored the baseline characteristics of the ATTRACTION-2 patients and extracted a single-factor and double-factor combinations associated with early disease progression or early death. In the extracted patient subgroups, the 3-year restricted mean survival times of progression-free survival and overall survival were compared between the nivolumab and placebo arms. Results Two single factors (age and peritoneal metastasis) were extracted as independent predictors of early progression, but none of them, as a single factor, stratified patients into two subgroups with significant differences in restricted mean survival time. In contrast, two double-factor combinations (serum sodium level and white blood cell count; serum sodium level and neutrophil–lymphocyte ratio) stratifying patients into two subgroups with significant differences in the restricted mean survival time were extracted. Additional exploratory analysis of a triple-factor combination showed that patients aged < 60 years with peritoneal metastasis and low serum sodium levels (approximately 7% of all patients) might receive less benefit from nivolumab, and patients aged ≥ 60 years with no peritoneal metastasis and normal serum sodium levels might receive higher benefit. Conclusions A combination of age, peritoneal metastasis, and serum sodium level might predict benefit from nivolumab as salvage therapy in advanced gastric or gastroesophageal junction cancer patients, especially less benefit for patients having all three risk factors.

Influence of high altitude on the expression of HIF-1 and on the prognosis of Ecuadorian patients with gastric adenocarcinoma

“…We considered a RMST difference, but not a RMST ratio, as the measure of effect because it may be intuitively understandable to clinicians. Comparisons between RMST adjusted for gender and age were made using an adjusted ANCOVA-type analysis, as proposed by Tian [24][25][26]. RMST values with 95% confidence intervals were estimated using the 'survRM2' package of the R programming language.…”

Predictive biomarkers for the efficacy of nivolumab as ≥ 3rd-line therapy in patients with advanced gastric cancer: a subset analysis of ATTRACTION-2 phase III trial

“…In 24 AMC patients with measurable lesion and available tissue analysis results, PD-L1 (CPS ≥ 1%) as well as low blood NLR and normal serum Na at baseline were associated with higher ORR and DCR, while tumor EBV infection and high TMB in the tumor were not. This study is a worthy study, despite a subgroup study, to complement the limitation of the post-hoc analysis of the ATTRACTION-2 study [ 10 ], which did not include tumor-tissue based biomarkers analysis. The predictive value of both baseline blood NLR and serum Na, which were extracted as double-factor combination for prediction of benefit from nivolumab in the post-hoc analysis [ 10 ], was confirmed and could be considered to be robust, given these factors remained significant after multivariate analysis with tumor tissue-based biomarkers.…”

“…This study is a worthy study, despite a subgroup study, to complement the limitation of the post-hoc analysis of the ATTRACTION-2 study [ 10 ], which did not include tumor-tissue based biomarkers analysis. The predictive value of both baseline blood NLR and serum Na, which were extracted as double-factor combination for prediction of benefit from nivolumab in the post-hoc analysis [ 10 ], was confirmed and could be considered to be robust, given these factors remained significant after multivariate analysis with tumor tissue-based biomarkers. Furthermore, the predictive values of tumor tissue-based biomarkers, previously explored as promising, could be validated in this study.…”

“…Recently, the post hoc analysis from the ATTRACTION-2 study has been reported. This study explored the baseline clinical characteristics of the patients and extracted double factor combinations (serum Na and white blood cell count or neutrophil–lymphocyte ratio [NLR]) for prediction of benefit from nivolumab [ 10 ]. The triple factor combination, including age, peritoneal metastasis, and serum Na, also showed the significant association with benefit from nivolumab [ 10 ].…”

“…This study explored the baseline clinical characteristics of the patients and extracted double factor combinations (serum Na and white blood cell count or neutrophil–lymphocyte ratio [NLR]) for prediction of benefit from nivolumab [ 10 ]. The triple factor combination, including age, peritoneal metastasis, and serum Na, also showed the significant association with benefit from nivolumab [ 10 ]. A high blood NLR has been reported as a poor prognostic factor in a variety of cancers treated with chemotherapy [ 11 ] and also with immune checkpoint inhibitors [ 12 ].…”