Caris’s biomarker driven therapy demonstrates clinical benefit for nearly 30% of patients with difficult-to-treat metastatic gastric and oesophageal cancer
Gastric and oesophageal cancer are the third and sixth leading cause of cancer deaths worldwide, respectively. At present, there is no internationally accepted consensus regarding standard-of-care in the first-line metastatic gastric and oesophageal cancer setting (with the exception of HER-2 positive gastroesophageal junction cancer). Clinical outcomes remain poor for these cancers, and new treatment approaches are needed. 1
Precision treatment of cancer identifies biomarkers to tailor therapeutic regimens for each patient. The strength of the Caris approach lies in the combination of molecular methodologies assessing DNA, RNA and proteins to identify actionable biomarkers, namely, the use of immunohistochemistry (IHC), fluorescence/chromogenic in-situ hybridization (FISH/CISH), microarray analyses, sequencing/next-generation sequencing (NGS), and RNA-sequencing.1
This Israeli-based multi-centre study retrospectively evaluated the real-life clinical experience of 46 patients with metastatic gastric or oesophageal cancer, who underwent biomarker analysis using Caris Molecular Intelligence (CMI) tumour profiling service between January 2010 and March 2014. 61% of these patients were male (n=28) and the median age was 58 years. The most common tumour site was the cardia (39.1%) and the most common histologic type was adenocarcinoma (87%). The majority of patients had poorly differentiated tumours (56.5%).1
Caris’ tumour profiling service identified actionable biomarkers for all 46 patients. Of the 46 patients, 28 were treated with chemotherapy/biologic agents after the analysis results. 27 of these (96.4%) received biomarker driven therapy. In the line of first therapy, five patients (17.9%) achieved a partial response, five (17.9%) stable disease, 16 (57.1%) progressive disease, and two (7.1%) were non-evaluable. 24 patients were eligible for progression-free survival ratio analysis (PFS), with the median PFS in the first line being 129 days (range, 12-1155 days). In seven of these patients (29.2%), the ratio between the longest PFS after the biomarker analysis and the PFS on their last regimen before the biomarker analysis was ³ 1.3 (the standard threshold used to determine when treatment was considered beneficial). A one-sided exact binomial test rejected the null hypothesis (p=0.019), where H0 was that ≤15% of patients would gain such benefit.1
This study is the first study to evaluate the potential clinical value of biomarker-driven therapy in metastatic gastric and oesophageal cancers. Findings from this research are aligned with those from other recent studies describing the potential benefit of biomarker driven therapy, including studies in numerous tumour types such as pancreatic, breast, salivary gland, and others.2-7
Limitations to this study were its retrospective design and its small sample size, which does not allow further analysis by clinic-pathologic or molecular parameters. A key strength to this study is that it stems from real-life clinical practice.
- A recently published, retrospective study in real-life clinical practice demonstrated clinical benefit using biomarker driven therapy for 29.2% of patients with metastatic gastric and oesophageal cancer.
- The median PFS in the first line of biomarker driven therapy was 129 days (range, 12-1155).
- Findings of this study were aligned with other recent studies assessing the potential benefit of biomarker driven therapy in pancreatic, breast, salivary gland, and other types of cancer.
- Purim O, Beny A, Inbar M, et al. Biomarker-driven therapy in metastatic gastric and esophageal cancer: Real-life clinical experience. Target Oncol. 2018 Apr;13(2):217-226. [PDF]
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- Barrett MT, Lenkiewicz E, Evers L, et al. Phase II study of therapy selected by molecular profiling in patients with previously treated metastatic pancreatic cancer – SU2C-001. Cancer Res. 2012;72(8 suppl):3697. [URL]
- Popovtzer A, Sarfaty M, Limon D, et al. Metastatic salivary gland tumors: A single-center study demonstrating the feasibility and potential clinical benefit of molecular-profiling-guided therapy. Biomed Res Int. 2015;2015:614845. [URL]
- Epelbaum R, Shacham-Shmueli E, Klein B, et al. Molecular profiling-selected therapy for treatment of advanced pancreaticobiliary cancer: A retrospective multicenter study. Biomed Res Int. 2015;2015:681653. [URL]
- Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998-2006. [URL]
- Park HS, Lim SM, Kim S, et al. Pilot study of a next-generation sequencing-based targeted anticancer therapy in refractory solid tumors at a Korean Institution. PLoS One. 2016 Apr 22;11(4):e0154133. [URL]