TY - JOUR
T1 - Epidermal Growth Factor Receptor Inhibition in Epidermal Growth Factor Receptor-Amplified Gastroesophageal Cancer
T2 - Retrospective Global Experience
AU - Maron, Steven B.
AU - Moya, Stephanie
AU - Morano, Federica
AU - Emmett, Matthew J.
AU - Chou, Joanne F.
AU - Sabwa, Shalom
AU - Walch, Henry
AU - Peterson, Bryan
AU - Schrock, Alexa B.
AU - Zhang, Liangliang
AU - Janjigian, Yelena Y.
AU - Chalasani, Sree
AU - Ku, Geoffrey Y.
AU - Disel, Umut
AU - Enzinger, Peter
AU - Uboha, Nataliya
AU - Kato, Shumei
AU - Yoshino, Takayuki
AU - Shitara, Kohei
AU - Nakamura, Yoshiaki
AU - Saeed, Anwaar
AU - Kasi, Pashtoon
AU - Chao, Joseph
AU - Lee, Jeeyun
AU - Capanu, Marinela
AU - Wainberg, Zev
AU - Petty, Russell
AU - Pietrantonio, Filippo
AU - Klempner, Samuel J.
AU - Catenacci, Daniel V. T.
N1 - Funding Information:
Supported by the National Cancer Institute: K12 CA184776 (S.B.M.) and P30 CA008748 (Memorial Sloan Kettering).
Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2022/8/1
Y1 - 2022/8/1
N2 - Purpose: Subset analyses from phase III evaluation of epidermal growth factor receptor inhibition (EGFRi) suggest improved outcomes in patients with EGFR-amplified gastroesophageal adenocarcinoma (GEA), but large-scale analyses are lacking. This multi-institutional analysis sought to determine the role of EGFRi in the largest cohort of patients with EGFR-amplified GEA to date.Patients and Methods: A total of 60 patients from 15 tertiary cancer centers in six countries met the inclusion criteria. These criteria required histologically confirmed GEA in the metastatic or unresectable setting with EGFR amplification identified by using a Clinical Laboratory Improvement Amendments-approved assay, and who received on- or off-protocol EGFRi. Testing could be by tissue next-generation sequencing, plasma circulating tumor DNA next-generation sequencing, and/or fluorescence in situ hybridization performed by a Clinical Laboratory Improvement Amendments approved laboratory. Treatment patterns and outcomes analysis was also performed using a deidentified clinicogenomic database (CGDB).Results: Sixty patients with EGFR-amplified GEA received EGFRi, including 31 of 60 patients (52%) with concurrent chemotherapy. Across treatment lines, patients achieved a 43% objective response rate with a median progression-free survival of 4.6 months (95% CI, 3.5 to 6.4). Patients receiving EGFRi in first-, second-, and third-line therapy achieved a median overall survival of 20.6 months (95% CI, 13.5 to not reached [NR]), 9 months (95% CI, 7.9 to NR), and 8.4 months (7.6 to NR), respectively. This survival far exceeded the 11.2-month (95% CI, 8.7 to 14.2) median overall survival from first-line initiation of non-EGFRi therapy in patients with EGFR-amplified GEA in the CGDB. Despite this benefit, analysis of the CGDB (January 2011-December 2020) suggests that only 5% of patients with EGFR-amplified GEA received EGFRi.Conclusion: Patients with EGFR-amplified GEA derive significant benefit from EGFRi. Further prospective investigation of EGFRi in a well-selected patient population is ongoing in an upcoming trial of amivantamab in EGFR and/or MET amplified GEA.
AB - Purpose: Subset analyses from phase III evaluation of epidermal growth factor receptor inhibition (EGFRi) suggest improved outcomes in patients with EGFR-amplified gastroesophageal adenocarcinoma (GEA), but large-scale analyses are lacking. This multi-institutional analysis sought to determine the role of EGFRi in the largest cohort of patients with EGFR-amplified GEA to date.Patients and Methods: A total of 60 patients from 15 tertiary cancer centers in six countries met the inclusion criteria. These criteria required histologically confirmed GEA in the metastatic or unresectable setting with EGFR amplification identified by using a Clinical Laboratory Improvement Amendments-approved assay, and who received on- or off-protocol EGFRi. Testing could be by tissue next-generation sequencing, plasma circulating tumor DNA next-generation sequencing, and/or fluorescence in situ hybridization performed by a Clinical Laboratory Improvement Amendments approved laboratory. Treatment patterns and outcomes analysis was also performed using a deidentified clinicogenomic database (CGDB).Results: Sixty patients with EGFR-amplified GEA received EGFRi, including 31 of 60 patients (52%) with concurrent chemotherapy. Across treatment lines, patients achieved a 43% objective response rate with a median progression-free survival of 4.6 months (95% CI, 3.5 to 6.4). Patients receiving EGFRi in first-, second-, and third-line therapy achieved a median overall survival of 20.6 months (95% CI, 13.5 to not reached [NR]), 9 months (95% CI, 7.9 to NR), and 8.4 months (7.6 to NR), respectively. This survival far exceeded the 11.2-month (95% CI, 8.7 to 14.2) median overall survival from first-line initiation of non-EGFRi therapy in patients with EGFR-amplified GEA in the CGDB. Despite this benefit, analysis of the CGDB (January 2011-December 2020) suggests that only 5% of patients with EGFR-amplified GEA received EGFRi.Conclusion: Patients with EGFR-amplified GEA derive significant benefit from EGFRi. Further prospective investigation of EGFRi in a well-selected patient population is ongoing in an upcoming trial of amivantamab in EGFR and/or MET amplified GEA.
U2 - 10.1200/JCO.21.02453
DO - 10.1200/JCO.21.02453
M3 - Article
C2 - 35349370
SN - 0732-183X
VL - 40
SP - 2458
EP - 2467
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 22
ER -