For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
39
views
25
references
 Top references
cited by
3
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      261
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Durable clinical benefit to trastuzumab and chemotherapy in a patient with metastatic colon adenocarcinoma harboring ERBB2 amplification

      case-report

      Read this article at

      ScienceOpenPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Somatic ERBB2 amplification or activating mutations occur in approximately 2–5% of metastatic colorectal adenocarcinomas and are presumed to be oncogenic drivers, but limited evidence exists to suggest these lesions are sensitive to targeted monotherapy in patients. Here we present the case of a patient with advanced CRC with pulmonary metastases, who had progressed on both standard of care cytotoxic chemotherapy and anti- EGFR targeted therapy. Comprehensive genomic profiling (FoundationOne ®) identified amplification of ERBB2 and a TP 53 mutation in the metastatic lesion. Treatment with trastuzumab with a chemotherapy backbone elicited stable disease/minor response in the patient over a one year course of therapy, reducing tumor burden and significantly improving quality of life. This report demonstrates the application of personalized targeted therapy guided by comprehensive genomic profiling in metastatic colorectal adenocarcinoma.

          Related collections

          Most cited references25

          • Record: found
          • Abstract: found
          • Article: not found

          TAS-102 monotherapy for pretreated metastatic colorectal cancer: a double-blind, randomised, placebo-controlled phase 2 trial.

          Takayuki Yoshino, Nobuyuki Mizunuma, Kentaro Yamazaki … (2012)
          Treatments that confer survival benefit are needed in patients with heavily pretreated metastatic colorectal cancer. The aim of this trial was to investigate the efficacy and safety of TAS-102-a novel oral nucleoside antitumour agent. Between August 25, 2009, and April 12, 2010, we undertook a multicentre, double-blind, randomised, placebo-controlled phase 2 trial in Japan. Eligible patients were 20 years or older; had confirmed colorectal adenocarcinoma; had a treatment history of two or more regimens of standard chemotherapy; and were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin. Patients had to be able to take oral drugs; have measurable lesions; have an Eastern Cooperative Oncology Group performance status of between 0 and 2; and have adequate bone-marrow, hepatic, and renal functions within 7 days of enrolment. Patients were randomly assigned (2:1) to either TAS-102 (35 mg/m(2) given orally twice a day in a 28-day cycle [2-week cycle of 5 days of treatment followed by a 2-day rest period, and then a 14-day rest period]) or placebo; all patients received best supportive care. Randomisation was done with minimisation methods, with performance status as the allocation factor. The randomisation sequence was generated with a validated computer system by an independent team from the trial sponsor. Investigators, patients, data analysts, and the trial sponsor were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. Safety analyses were done in the per-protocol population. The study is in progress and is registered with Japan Pharmaceutical Information Center, number JapicCTI-090880. 112 patients allocated to TAS-102 and 57 allocated to placebo made up the intention-to-treat population. Median follow-up was 11·3 months (IQR 10·7-14·0). Median overall survival was 9·0 months (95% CI 7·3-11·3) in the TAS-102 group and 6·6 months (4·9-8·0) in the placebo group (hazard ratio for death 0·56, 80% CI 0·44-0·71, 95% CI 0·39-0·81; p=0·0011). 57 (50%) of 113 patients given TAS-102 in the safety population had neutropenia of grade 3 or 4, 32 (28%) leucopenia, and 19 (17%) anaemia. No patient given placebo had grade 3 or worse neutropenia or leucopenia; three (5%) of 57 had grade 3 or worse anaemia. Serious adverse events occurred in 21 (19%) patients in the TAS-102 group and in five (9%) in the placebo group. No treatment-related deaths occurred. TAS-102 has promising efficacy and a manageable safety profile in patients with metastatic colorectal cancer who are refractory or intolerant to standard chemotherapies. Copyright © 2012 Elsevier Ltd. All rights reserved.
          Article 0 comments Cited 107 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Level of HER2 gene amplification predicts response and overall survival in HER2-positive advanced gastric cancer treated with trastuzumab.

            Lilia M Sierra-Galan, Francesc Pons, Antonieta Salud … (2013)
            Previous studies have highlighted the importance of an appropriate human epidermal growth factor receptor 2 (HER2) evaluation for the proper identification of patients eligible for treatment with anti-HER2 targeted therapies. Today, the relationship remains unclear between the level of HER2 amplification and the outcome of HER2-positive gastric cancer treated with first-line chemotherapy with trastuzumab. The aim of this study was to determine whether the level of HER2 gene amplification determined by the HER2/CEP17 ratio and HER2 gene copy number could significantly predict some benefit in overall survival and response to therapy in advanced gastric cancer treated with trastuzumab-based chemotherapy. Ninety patients with metastatic gastric cancer treated with first-line trastuzumab-based chemotherapy were studied. The optimal cutoff values for HER2/CEP17 ratio and HER2 gene copy number (GCN) for discriminating positive results in terms of response and prolonged survival were determined using receiver operating characteristic curves analyses. In this study, a median HER2/CEP17 ratio of 6.11 (95% CI, 2.27 to 21.90) and a median HER2 gene copy number of 11.90 (95% CI, 3.30 to 43.80) were found. A mean HER2/CEP17 ratio of 4.7 was identified as the optimal cutoff value discriminating sensitive and refractory patients (P = .005). Similarly, the optimal cutoff for predicting survival longer than 12 months was 4.45 (P = .005), and for survival longer than 16 months was 5.15 (P = .004). For HER2 GCN, the optimal cutoff values were 9.4, 10.0, and 9.5, respectively (P = .02). The level of HER2 gene amplification significantly predicts sensitivity to therapy and overall survival in advanced gastric cancer treated with trastuzumab-based chemotherapy.
            Article 0 comments Cited 66 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Trastuzumab.

              Jan Schellens, Jos H. Beijnen, Annelies H Boekhout (2010)
              Trastuzumab is standard of care in the treatment of human epidermal growth factor receptor (HER)-2⁺ early and advanced breast cancer. Recently, it has been approved for the treatment of HER-2⁺ advanced gastric cancer. Trastuzumab is an IgG1 humanized monoclonal antibody administered by intravenous infusion on a weekly or three weekly schedule. In all registered indications, trastuzumab is almost always given in combination with chemotherapy. In hormonal receptor-positive breast cancer in postmenopausal women, trastuzumab can be combined with an aromatase inhibitor. Main toxicity is reduction in the left ventricular ejection fraction, which in a minority of patients can become symptomatic, but in many patients is at least partly reversible. Long-term safety needs to be further determined.
              Article 0 comments Cited 33 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Oncoscience
                Journal ID (iso-abbrev): Oncoscience
                Journal ID (publisher-id): ImpactJ
                Title: Oncoscience
                Publisher: Impact Journals LLC
                ISSN (Electronic): 2331-4737
                Publication date Collection: 2015
                Publication date (Electronic): 1 July 2015
                Volume: 2
                Issue: 6
                Pages: 581-584
                Affiliations
                1 Adana Numune Education and Research Hospital, Department of Medical Oncology, Adana/Turkey
                2 Foundation Medicine, Inc. Cambridge, MA, USA
                3 Baskent University School of Medicine Adana, Turkey
                4 Albany Medical Center, Albany, NY
                5 University of Florida College of Medicine Gainesville, FL, USA
                Author notes
                Correspondence to: Umut Disel, doctorhope@ 123456gmail.com
                Article
                PMC ID: 4506361
                SO-VID: 03447df8-fc55-4abd-aa62-9e3d979660f4
                Copyright © Copyright: © 2015 Disel et al.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 15 June 2015
                Date accepted : 30 June 2015
                Categories
                Subject: Case Report

                Keywords: erbb2,her2,trastuzumab,oxaliplatin,colorectal adenocarcinoma
                Data availability:
                Keywords: erbb2, her2, trastuzumab, oxaliplatin, colorectal adenocarcinoma

                Comments

                Comment on this article

                Similar content261

                See all similar

                Cited by3

                See all cited by

                Most referenced authors369

                See all reference authors