LBA7_PR Nivolumab plus chemotherapy versus chemotherapy alone in patients with previously untreated advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer: ATTRACTION-4 (ONO-4538-37) study

Boku, Narikazu; Ryu, M.-H.; Oh, Do‐Youn; Oh, Sang Cheul; Chung, Hyun Cheol; Kw, Lee; Omori, Takeshi; Shitara, Kohei; Sakuramoto, S.; Chung, Ik Joo; Yamaguchi, Kensei; Katô, Katsuhiko; Sym, Sun Jin; Kadowaki, Shigenori; Tsuji, Kiichiro; Js, Chen; Bai, L-Y.; Lt, Chen; Kang, Yubin

doi:10.1016/j.annonc.2020.08.2297

Cited by 115 publications

(95 citation statements)

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“…These findings imply the linkage between ICD pathway and oxaliplatin efficacy, which can be coupled with the potential synergy of oxaliplatin and immunotherapy. 21 22 …”

Section: Discussionmentioning

confidence: 99%

Immunogenic cell death pathway polymorphisms for predicting oxaliplatin efficacy in metastatic colorectal cancer

Arai

Xiao

Loupakis

et al. 2020

J Immunother Cancer

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BackgroundImmunogenic cell death (ICD) is a tumor cell death involving both innate and adaptive immune responses. Given published findings that oxaliplatin, but not irinotecan, drives ICD, we investigated whether single nucleotide polymorphisms (SNPs) in the ICD pathway are associated with the efficacy of oxaliplatin-based chemotherapy in metastatic colorectal cancer (mCRC).MethodsTwo randomized clinical trials data were analyzed: discovery cohort, FOLFOX/bevacizumab arm (MAVERICC); validation cohort, FOLFOXIRI/bevacizumab arm (TRIBE); and two control cohorts, FOLFIRI/bevacizumab arms (both trials). Genomic DNA extracted from blood samples was genotyped. Ten SNPs in the ICD pathway were tested for associations with clinical outcomes.ResultsIn total, 648 patients were included. In the discovery cohort, three SNPs were significantly associated with clinical outcomes in univariate analysis: CALR rs1010222 with progression-free survival (G/G vs any A, HR=0.61, 95% CI 0.43–0.88), ANXA1 rs1050305 with overall survival (OS) (A/A vs any G, HR=1.87, 95% CI 1.04–3.35), and LRP1 rs1799986 with OS (C/C vs any T, HR=1.69, 95% CI 1.07–2.70). Multivariate analysis confirmed the trend, but statistical significance was not reached. In the validation cohort, ANXA1 rs1050305, and LRP1 rs1799986 were validated to have the significant associations with clinical outcome. No significant associations of these SNPs were observed in the two control cohorts. Treatment-by-SNP interaction test confirmed the predictive values.ConclusionsThe predictive utility of ICD-related SNPs for the efficacy of oxaliplatin-based chemotherapy was demonstrated, warranting further validation studies to be translated into personalized treatment strategies using conventional cytotoxic agents in mCRC.

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“…These findings imply the linkage between ICD pathway and oxaliplatin efficacy, which can be coupled with the potential synergy of oxaliplatin and immunotherapy. 21 22 …”

Section: Discussionmentioning

confidence: 99%

Immunogenic cell death pathway polymorphisms for predicting oxaliplatin efficacy in metastatic colorectal cancer

Arai

Xiao

Loupakis

et al. 2020

J Immunother Cancer

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“…The addition of nivolumab to chemotherapy improved mOS compared to chemotherapy alone (14.4 vs. 11.1 months, HR 0.71, 95% CI 0.59–0.86, p < 0.0001) in treatment-naive, CPS ≥ 5 GC based on interval analysis of the CheckMate649 study [ 43 ]. However, the ATTRACTION-4 study in Asian patients did not demonstrate OS benefits of the immunochemotherapy approach, but this cohort was heavily treated with multiple lines of therapies [ 42 ]. Subgroup analysis with MSI-H GC may shed light on the role of ICIs as a first-line treatment for this population.…”

Section: Gastric and Gastroesophageal Adenocarcinomamentioning

confidence: 99%

Management of Non-Colorectal Digestive Cancers with Microsatellite Instability

Zhu

Jin

Hubbard

2021

Cancers

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Microsatellite instability (MSI) is a hallmark of genetic predisposition to DNA damage. It arises from either germline or somatic events leading to impaired function of the mismatch repair system. It can be detected via genetic sequencing or immunohistochemistry with relatively high concordance rates. The presence of MSI in a tumor reflects a high neoantigen load and predicts favorable treatment response to immune checkpoint inhibitors (ICIs). In gastrointestinal cancers, MSI is a predictive biomarker for ICIs with potential prognostic impact but its clinical utility varies widely depending on tumor type. This may be explained by the complexity of tumor microenvironment as highlighted by recent translational studies. In this review, we will discuss the predictive and prognostic value of MSI status in non-colorectal cancers of the digestive system, important clinical trials involving ICIs and potential strategies to overcome resistance to immunotherapy.

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“…This observed result was also supported by ATTRACTION 4 trial that evaluated efficacy of nivo + chemo in Asian HER2-negative GC patients. 56,57 Both studies showed that ICI combined with chemo could be a potential first-line treatment option for patients with GC.…”

Section: F I G U R Ementioning

confidence: 99%

Clinical implications of plasma ctDNA features and dynamics in gastric cancer treated with HER2‐targeted therapies

Zhang

Chen

Chong

et al. 2020

Clinical & Translational Med

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• Plasma ctDNA-based diagnosis was more sensitive than conventional computed tomography scanning in 40% of patients, gaining time for clinical management. • Plasma tumor mutation burden was a potential marker to predict the therapeutic outcomes of human epidermal growth factor receptor 2 (HER2)targeted therapy in GC. • HER2-positive patients with high TMB might gain more therapeutic benefits from immunotherapy instead of HER2-targeted regimens that required further studies and validations.

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LBA7_PR Nivolumab plus chemotherapy versus chemotherapy alone in patients with previously untreated advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer: ATTRACTION-4 (ONO-4538-37) study

Cited by 115 publications

References 0 publications

Immunogenic cell death pathway polymorphisms for predicting oxaliplatin efficacy in metastatic colorectal cancer

Immunogenic cell death pathway polymorphisms for predicting oxaliplatin efficacy in metastatic colorectal cancer

Management of Non-Colorectal Digestive Cancers with Microsatellite Instability

Clinical implications of plasma ctDNA features and dynamics in gastric cancer treated with HER2‐targeted therapies

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