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Rapidly Evolving Treatment Landscape for Metastatic Esophagogastric Carcinoma: Review of Recent Data.

ABSTRACT: Esophagogastric cancer (EGC) is a heterogeneous group of malignancies that collectively represent the 2nd leading cause of cancer deaths worldwide. While surgery in combination with chemotherapy and/or radiation therapy represents the primary curative treatment for early stage disease, survival outcomes for the majority of patients with later-stage disease remain poor. Cytotoxic chemotherapy with platinum doublets such as 5-FU/leucovorin/oxaliplatin is the mainstay of treatment with incremental benefits provided by targeted therapy (trastuzumab, trastuzumab deruxtecan, ramucirumab) and immunotherapy (pembrolizumab, nivolumab). In this article, we provide an updated review and perspectives on the management of advanced EGC. We examine the distinct epidemiological, etiological and molecular features of each disease entity comprising EGC. After reviewing the critical studies that established conventional systemic cytotoxic and targeted therapeutics, we elaborate on recent promising and complex data with immune checkpoint inhibition focusing on implications of tumor histology and PD-L1 expression in the tumor microenvironment. We also highlight novel diagnostic and therapeutic strategies to build on these recent advances.

SUBMITTER: Kankeu Fonkoua LA

PROVIDER: S-EPMC8352646 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMetastatic urothelial carcinoma (mUC) historically is treated with first-line platinum-based combination chemotherapy, preferably cisplatin plus gemcitabine whenever possible. In recent years, multiple classes of targeted therapy have demonstrated benefit, with some receiving approval in mUC. This review will summarize phase III efficacy and safety data for targeted agents, principally immune checkpoint inhibitors (ICIs), as either first-line or first-line switch-maintenance therapy for mUC and interpret these findings in the context of the current treatment landscape.Materials and methodsPublished and presented phase III data on targeted therapy for the first-line or first-line switch-maintenance treatment of mUC were identified using the key search terms "targeted therapy" AND "urothelial carcinoma" AND "advanced" OR respective aliases according to the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).ResultsOf the six eligible phase III targeted therapy trials, two assessing ICIs met their primary endpoints in platinum-eligible patients. First-line ICI plus chemotherapy combinations have not improved overall survival (OS), although final OS results of the IMVigor 130 trial are pending. Switch-maintenance using an ICI in patients achieving at least stable disease following platinum-based chemotherapy statistically significantly improved OS (21.4 vs. 14.3 months, hazard ratio, 0.69; 95% confidence interval, 0.56-0.86; p = .001). Current sequencing options for mUC include first-line platinum-based chemotherapy with a switch to ICI either immediately or upon disease progression.ConclusionRecent targeted therapy trials have expanded ICI sequencing options for mUC. The treatment landscape is likely to evolve rapidly, with results from multiple phase III trials expected in the next 5 years.Implications for practiceMultiple classes of targeted agents are approved for use in metastatic urothelial carcinoma (mUC). Six phase III trials have recently provided insight on the benefit of these agents in the first-line setting. In platinum-eligible patients, immune checkpoint inhibitors (ICIs) combined with first-line platinum-based chemotherapy failed to demonstrate improved survival, although ICI monotherapy as switch-maintenance significantly improved overall survival in patients with mUC who had achieved at least stable disease following first-line platinum-based chemotherapy. In patients ineligible for any chemotherapy, pembrolizumab, atezolizumab, or pembrolizumab in combination with enfortumab vedotin may be options.

Project description:The approval of targeted therapies for metastatic colorectal cancer (mCRC) has led to important improvements in patient outcomes. However, it is still necessary to increase individualisation of treatments based on tumour genetic profiles to optimise efficacy, while minimising toxicity. As such, there is currently great focus on the discovery and validation of further biomarkers in mCRC, with many new potential prognostic and predictive markers being identified alongside developments in patient molecular profiling technologies. Here, we review data for validated and emerging biomarkers impacting treatment strategies in mCRC. We completed a structured literature search of the PubMed database to identify relevant publications, limiting for English-language publications published between 1 January 2014 and 11 July 2018. In addition, we performed a manual search of the key general oncology and CRC-focused congresses to identify abstracts reporting emerging mCRC biomarker data, and of ClinicalTrials.gov to identify ongoing clinical trials investigating emerging biomarkers in mCRC and/or molecular-guided clinical trials. There is solid evidence supporting the use of BRAF status as a prognostic biomarker and DYPD, UGT1A1, RAS, and microsatellite instability as predictive biomarkers in mCRC. There are a number of emerging biomarkers that may prove to be clinically relevant in the future to have prognostic (HPP1 methylation), predictive (HER3, microRNAs, anti-angiogenic markers, and CRC intrinsic subtypes), or both prognostic and predictive values (HER2, CpG island methylator phenotype, tumour mutational load, gene fusions, and consensus molecular subtypes). As such, new biomarker-led treatment strategies in addition to anti-epidermal growth factor receptor and anti-angiogenetic treatments are being explored. Biomarkers that are not recommended to be tested in clinical practice or are unlikely to be imminently clinically relevant for mCRC include thymidylate transferase, ERCC1, PIK3CA, and PTEN. We highlight the clinical utility of existing and emerging biomarkers in mCRC and provide recommended treatment strategies according to the biomarker status. An update on ongoing molecular-guided clinical trials is also provided.

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Rapidly Evolving Treatment Landscape for Metastatic Esophagogastric Carcinoma: Review of Recent Data.

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