Biomarker-Driven Therapy in Metastatic Gastric and Esophageal Cancer: Real-Life Clinical Experience

Abstract

BackgroundPrecision treatment of cancer uses biomarker-driven therapy to individualize and optimize patient care.ObjectiveTo evaluate real-life clinical experience with biomarker-driven therapy in metastatic gastric and esophageal cancer in Israel.Patients and MethodsThis multicenter retrospective cohort study included patients with metastatic gastric or esophageal cancer who were treated in the participating institutions and underwent biomarker-driven therapy. Treatment was considered to have a benefit if the ratio between the longest progression-free survival (PFS) post biomarker-driven therapy and the last PFS before the biomarker-driven therapy was ≥1.3. The null hypothesis was that ≤15% of patients gain such benefit.ResultsThe analysis included 46 patients (61% men; median age, 58 years; 57% with poorly-differentiated tumors). At least one actionable (i.e., predictive of response to a specific therapy) biomarker was identified for each patient. Immunohistochemistry was performed on all samples and identified 1–8 (median: 3) biomarkers per patient (most commonly: low TS, high TOPO1, high TOP2A). Twenty-eight patients received therapy after the biomarker analysis (1–4 lines). In the 1st line after biomarker analysis, five patients (18%) achieved a partial response and five (18%) stable disease; the median (range) PFS was 129 (12–1155) days. Twenty-four patients were evaluable for PFS ratio analysis; in seven (29.2%), the ratio was ≥1.3. In a one-sided exact binomial test vs. the null hypothesis, p = 0.019; therefore, the null hypothesis was rejected.ConclusionsOur findings demonstrated that implementing biomarker-driven analysis is feasible and could provide clinical benefit for a considerable proportion (~30%) of patients with metastatic gastric or esophageal cancer.

Integrated Analysis of Hub Genes and Pathways In Esophageal Carcinoma Based on NCBI’s Gene Expression Omnibus (GEO) Database: A Bioinformatics Analysis

“…TOP2A controls topological states of DNA, a crucial role for proper segregation of daughter chromosomes during mitosis and meiosis [ 50 ]. One clinical study suggested that high TOP2A could serve as a biomarker driving medical therapy [ 51 ]. Another study showed that the knockdown of the long noncoding RNA (lncRNA) DDX11-AS1 reversed paclitaxel (PTX) resistance by means of inhibiting the expression level of TOP2A [ 52 ].…”

Value of Multiplatform Molecular Profiling (MMP) of Tumors in Clinical Practice

“…Following this pivotal study, the CMI MMP approach was incorporated into clinical practice, and reports describing additional analyses focusing on the utility of this approach were published/presented. Table 2 summarizes the Von Hoff study as well as 10 subsequent studies conducted worldwide (US, Austria, Australia, Israel, Lebanon, and Egypt) [13][14][15][16][17][18][19][20][21][22][23] . Some of these studies investigated advanced disease in specific tumor types such as gastric/esophageal 14 , pancreatic/pancreaticobiliary 15,16 , breast 17 , and salivary glands cancer 18 , whereas other studies included a variety of refractory solid cancers including rare tumors [19][20][21][22][23] .…”

“…All the studies reported on clinical benefit. In 7 studies (involving a total of 218 evaluable patients) the PFS ratio endpoint was used, and the clinical benefit rate ranged from 27% to 59.5% [13][14][15]17,19,22,23 . In the remaining 4 studies (involving a total of 127 evaluable patients), other outcome measures were used such as response rate (complete response [CR] rate plus partial response [PR] rate), disease control rate (CR plus PR plus stable disease [SD] rate), and 1-year survival rate.…”

“…MMP-guided treatment was associated with clinical benefit in a considerable proportion of patients (20%-73%) in these 4 studies as well 16,18,20,21 . Although the studies were consistent in demonstrating that MMP provides relevant biomarker information, modifies treatment decisions, and facilitates extension of PFS [13][14][15][16][17][18][19][20][21][22][23] , they were limited by relatively modest cohort sizes, and some also by their retrospective design.…”

Multi-platform Tumour Profiling Delivers the Highest Clinical Utility and Improves Patient Outcomes in Today's Routine Clinical Practice

“…If the observed PFS ratio was greater than 1.3 (indicating a 30% increase in PFS with profiling-guided treatment), the patient was considered to have clinical benefit. Nine other physician-led evaluations of CMI have been conducted globally in a variety of solid tumours [21][22][23][24][25][26][27][28]. The definition of clinical benefit differed between studies and includedPFS ratio as described by von Hoff to more traditional endpoints such as disease control rate, response or overall survival greater than 6 months.…”