TY - JOUR
T1 - Targeting ERBB2 (HER2) amplification identified by next-generation sequencing in patients with advanced or metastatic solid tumors beyond conventional indications
AU - Dumbrava, Ecaterina E.Ileana
AU - Balaji, Kavitha
AU - Raghav, Kanwal
AU - Hess, Kenneth
AU - Javle, Milind
AU - Blum-Murphy, Mariela
AU - Ajani, Jaffer
AU - Kopetz, Scott
AU - Broaddus, Russell
AU - Routbort, Mark
AU - Demirhan, Mehmet
AU - Zheng, Xiaofeng
AU - Pant, Shubham
AU - Tsimberidou, Apostolia M.
AU - Subbiah, Vivek
AU - Hong, David S.
AU - Rodon, Jordi
AU - Shaw, Kenna M.
AU - Piha-Paul, Sarina A.
AU - Meric-Bernstam, Funda
N1 - Funding Information:
Supported, in part, by the Cancer Prevention Research Institute of Texas Precision Oncology Decision Support Core Grant No. RP150535, Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, Foundation Medicine, Guardant Health, National Center for Advancing
Publisher Copyright:
© 2019 by American Society of Clinical Oncology.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
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U2 - 10.1200/PO.18.00345
DO - 10.1200/PO.18.00345
M3 - Article
C2 - 32923865
AN - SCOPUS:85086265879
SN - 2473-4284
VL - 2
JO - JCO Precision Oncology
JF - JCO Precision Oncology
ER -