Targeting ERBB2 (HER2) Amplification Identified by Next-Generation Sequencing in Patients With Advanced or Metastatic Solid Tumors Beyond Conventional Indications
| Autor: | Shubham Pant, Funda Meric-Bernstam, Vivek Subbiah, Kenna M. Shaw, Kenneth R. Hess, Xiaofeng Zheng, Kavitha Balaji, Jaffer A. Ajani, Mark J. Routbort, Scott Kopetz, Mariela Blum-Murphy, Kanwal Pratap Singh Raghav, Russell Broaddus, Mehmet Esat Demirhan, Milind Javle, David S. Hong, Apostolia Maria Tsimberidou, Jordi Rodon, Sarina Anne Piha-Paul, Ecaterina Ileana Dumbrava |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research biology business.industry Gastroesophageal Junction DNA sequencing 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Text mining Oncology 030220 oncology & carcinogenesis Cancer research biology.protein Medicine Erbb2 her2 In patient Epidermal growth factor receptor skin and connective tissue diseases business |
| Zdroj: | JCO Precision Oncology. :1-12 |
| ISSN: | 2473-4284 |
| DOI: | 10.1200/po.18.00345 |
| Popis: | PURPOSE Human epidermal growth factor receptor 2 (HER2) is an effective therapeutic target in breast and gastric and gastroesophageal junction cancers. However, less is known about the prevalence of ERBB2 ( HER2) amplification and the efficacy of HER2-targeted treatment in other tumors. PATIENTS AND METHODS We assessed HER2 amplification status among 5,002 patients with advanced disease (excluding breast cancer) who underwent next-generation sequencing. We evaluated the clinical benefit of HER2-targeted therapy by measuring the time-dependent overall survival (OS) from the genomic testing results, progression-free survival (PFS), and PFS during HER2-targeted therapy (PFS2) compared with PFS during prior therapy (PFS1). RESULTS Overall, 122 patients (2.4%) had HER2 amplification, including patients with endometrial (5.3%), bladder (5.2%), biliary or gallbladder (4.9%), salivary (4.7%), and colorectal cancer (3.6%). Forty patients (38%) with nongastric, nongastroesophageal junction, or nonesophageal cancers received at least one line of HER2-targeted therapy. Patients receiving HER2-targeted therapy had a median OS of 18.6 months, compared with 10.9 months for patients who did not receive HER2-targeted therapy ( P = .070). On multivariable analysis, HER2-targeted therapy was significantly associated with increased OS (hazard ratio, 0.5; 95% CI, 0.27 to 0.93; P = .029), regardless of sex, age, or number of prior lines of treatment. The PFS2-to-PFS1 ratio was 1.3 or greater in 21 (57%) of 37 patients who received HER2-targeted therapy not in the first line of systemic treatment, and the median PFS2 and PFS1 times were 24 and 13 weeks, respectively ( P < .001). CONCLUSION HER2 amplifications using next-generation sequencing can be identified in a variety of tumor types. HER2-targeted therapy may confer clinical benefit in tumor types other than those for which HER2 inhibitors are approved. |
| Databáze: | OpenAIRE |
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