Precision Medicine to Treat Advanced Gastroesophageal Adenocarcinoma: A Work in Progress

Gambardella, Valentina; Fleitas, Tania; Tarazona, Noelia; Papaccio, Federica; Huerta, Marisol; Roselló, Susana; Gimeno-Valiente, Francisco; Roda, Desamparados

doi:10.3390/jcm9093049

Cited by 19 publications

(15 citation statements)

References 92 publications

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“…The development and introduction of immune checkpoint inhibitors (ICIs) in GC has spurred a growing interest in combination strategies including ICIs and HER2 -targeted treatments [ 30 ]. In fact, preclinical studies have suggested a synergistic activity for the combinations including trastuzumab and PD-1 inhibitors, resulting in T-cell activation and enhancing Antibody Dependent Cellular Phagocytosis (ADCC) in murine models [ 31 ].…”

Section: Trastuzumab the Toga Trial And Resistance Mechanismsmentioning

confidence: 99%

Novel HER2-Directed Treatments in Advanced Gastric Carcinoma: AnotHER Paradigm Shift?

Ricci

Rizzo

Llimpe

et al. 2021

Cancers

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Human epidermal growth factor receptor 2 (HER2) is overexpressed and/or amplified in approximately 15–20% of gastric adenocarcinoma (GC) patients. In 2010, the landmark ToGA trial established the combination of trastuzumab plus chemotherapy as the first-line standard of care for HER2-positive GC patients with advanced disease. However, subsequent studies on HER2 targeted therapies in this setting failed to meet their primary endpoints, and not all HER2-positive GC patients benefit from targeted approaches. More recently, novel HER2-directed treatments have been investigated, including trastuzumab deruxtecan (T-Dxd); following the results of the DESTINY-Gastric01 study, T-Dxd received its first U.S. Food and Drug Administration (FDA) approval on 15 January 2021 for the treatment of adults with unresectable, locally advanced, or metastatic GC who have received a prior trastuzumab-based regimen. In this review, we discuss the current HER2-targeted treatments for GC in the advanced disease setting, mainly focusing on emerging new treatments and future research directions.

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Section: Trastuzumab the Toga Trial And Resistance Mechanismsmentioning

confidence: 99%

Novel HER2-Directed Treatments in Advanced Gastric Carcinoma: AnotHER Paradigm Shift?

Ricci

Rizzo

Llimpe

et al. 2021

Cancers

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“…In fact, surgery is not an option in case of metastatic disease, especially to the bone. A detailed description of the currently recommended treatments for metastatic GC disease and/or future perspectives is not in the aim of this review; however, you can refer to dedicated literature and guidelines [ 3 , 4 , 5 , 12 , 76 ] for detailed coverage.…”

Section: Clinical Management Of Metastatic Gastric Cancer Patients Wimentioning

confidence: 99%

“…However, the journey to discover the molecular mechanisms that control GC behavior has just started. Recently, the molecular classifications of GC have depicted a very complex landscape [ 13 , 14 ] and multiple molecules, which could be eventually targeted by specific treatments, have been identified [ 4 , 5 ]. Among those molecules, the investigation regarding the role of antiangiogenic agents and multikinase inhibitors, such as cabozantinib, might be interesting future frontiers in the control of bone metastasis also in GC, as shown in other types of tumors, such as renal cancer [ 147 ].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…Although over the last decades the research in GC has focused on the role of novel and targeted treatments, chemotherapy based on a doublet with platin and fluorouracil remains the standard of care for the first-line therapy in case of metastatic disease without overexpression of human epithelial growth factor 2 receptor (HER2) [ 3 ]. To date, trastuzumab is the unique target agent approved for first-line treatment of HER2-positive metastatic GC in addition to the doublet chemotherapy backbone, due to the fact that all the other targeted agents failed to improve survival outcomes in this setting [ 4 , 5 ]. Recently, the immune checkpoint inhibitors have shown promising results in the treatment of first-line metastatic GC [ 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Bone Metastases from Gastric Cancer: What We Know and How to Deal with Them

Petrillo

Giunta

Pappalardo

et al. 2021

JCM

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Gastric cancer (GC) is the third cause of cancer-related death worldwide; the prognosis is poor especially in the case of metastatic disease. Liver, lymph nodes, peritoneum, and lung are the most frequent sites of metastases from GC; however, bone metastases from GC have been reported in the literature. Nevertheless, it is unclear how the metastatic sites may affect the prognosis. In particular, knowledge about the impact of bone metastases on GC patients’ outcome is scant, and this may be related to the rarity of bone lesions and/or their underestimation at the time of diagnosis. In fact, there is still a lack of specific recommendation for their detection at the diagnosis. Then, the majority of the evidences in this field came from retrospective analysis on very heterogeneous study populations. In this context, the aim of this narrative review is to delineate an overview about the evidences existing about bone metastases in GC patients, focusing on their incidence and biology, the prognostic role of bone involvement, and their possible implication in the treatment choice.

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“…Adenocarcinoma is the most common histological type, and gastric cancer or gastroesophageal junction adenocarcinoma (G/GEA), with or without esophageal adenocarcinoma, are commonly studied within the same clinical trials [2]. Developments in treatment for locally advanced and unresectable/metastatic G/GEA lag behind other solid malignancies, with a median survival of less than 1 year [3–5].…”

Section: Introductionmentioning

confidence: 99%

Toward a Treatment Sequencing Strategy: A Systematic Review of Treatment Regimens in Advanced Gastric Cancer/Gastroesophageal Junction Adenocarcinoma

et al. 2021

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Background. Platinum and fluoropyrimidine combinations typically comprise first-line (1L) therapy in advanced gastric cancer or gastroesophageal junction adenocarcinoma (G/GEA), although controversy exists regarding the use of doublet versus triplet cytotoxic regimens. Historically, second-line (2L) and third-line or later (3L+) therapy has been fragmented. Recent trials have increased the need for optimal treatment sequencing in advanced G/GEA. Materials and Methods. We conducted a systematic search of peer-reviewed manuscripts of randomized clinical trials examining 1L, 2L, and 3L+ therapy for advanced G/GEA published from 2009 through November 19, 2019. When available, overall survival, progression-free survival, time to progression, overall response rate, and toxicity were extracted from each and compared descriptively.Results. In 1L therapy, chemotherapy triplets demonstrated variable efficacy improvements with invariable increased toxicity compared to platinum/fluoropyrimidine doublets. Currently, the only published report of positive outcomes using biologics in 1L is adding trastuzumab in HER2+ advanced G/GEA. In 2L, doublet chemotherapy regimens are not uniformly more efficacious than single-agent taxanes or irinotecan, and ramucirumab has demonstrated improved outcomes as both monotherapy or combination. Conclusion.For advanced G/GEA, review of trial results from 2009-2019 support 1L therapy with platinum and fluoropyrimidine and sequencing with taxanes or irinotecan in combination with biologics as effective 2L options. Escalating to a triplet may add some efficacy at the expense of added toxicity. The Oncologist 2021;9999:• • Implications for Practice: The rapidly changing treatment landscape for advanced gastric cancer includes increasing options for refractory disease. With multiple first-line platinum-based regimens, identification of those with the best benefit-to-risk ratio may provide guidance on treatment sequencing strategies. Herein, we present findings from the published literature of randomized controlled trials that included a first-line platinum/fluoropyrimidine combination and, for second-line trials, patients with platinum/fluoropyrimidine-refractory disease. This guiding summary could be a tool for clinicians to identify the optimal first-line regimen(s) followed by a strategy for subsequent regimens.

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Precision Medicine to Treat Advanced Gastroesophageal Adenocarcinoma: A Work in Progress

Cited by 19 publications

References 92 publications

Novel HER2-Directed Treatments in Advanced Gastric Carcinoma: AnotHER Paradigm Shift?

Novel HER2-Directed Treatments in Advanced Gastric Carcinoma: AnotHER Paradigm Shift?

Bone Metastases from Gastric Cancer: What We Know and How to Deal with Them

Toward a Treatment Sequencing Strategy: A Systematic Review of Treatment Regimens in Advanced Gastric Cancer/Gastroesophageal Junction Adenocarcinoma

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