James Chih-Hsin Yang1, Martin Schuler2, Sanjay Popat3, Satoru Miura4, Simon Heeke5, Keunchil Park6, Angela Märten7, Edward S Kim8. 1. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: chihyang@ntu.edu.tw. 2. West German Cancer Center, University Duisburg-Essen and German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany. 3. Lung Unit, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; The Institute of Cancer Research, London, United Kingdom. 4. Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan. 5. Laboratory of Clinical and Experimental Pathology, Centre Hospitalier Universitaire de Nice, University Hospital Federation OncoAge, Nice, France. 6. Division of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 7. Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. 8. Department of Solid Tumor Oncology, Levine Cancer Institute, Atrium Health, Charlotte, North Carolina.
Abstract
INTRODUCTION: Limited clinical data are available regarding the efficacy of EGFR tyrosine kinase inhibitors (EGFR TKIs) in patients with NSCLC harboring uncommon EGFR mutations. This pooled analysis assessed the activity of afatinib in 693 patients with tumors harboring uncommon EGFR mutations treated in randomized clinical trials, compassionate-use and expanded-access programs, phase IIIb trials, noninterventional trials, and case series or studies. METHODS: Patients had uncommon EGFR mutations, which were categorized as follows: (1) T790M; (2) exon 20 insertions; (3) "major" uncommon mutations (G719X, L861Q, and S768I, with or without any other mutation except T790M or an exon 20 insertion); (4) compound mutations; and (5) other uncommon mutations. Key end points were overall response rate (ORR), duration of response, and time to treatment failure (TTF). RESULTS: In EGFR TKI-naive patients (n = 315), afatinib demonstrated activity against major uncommon mutations (median TTF = 10.8 mo; 95% confidence interval [CI]: 8.1-16.6; ORR = 60.0%), compound mutations (median TTF = 14.7 mo; 95% CI: 6.8-18.5; ORR = 77.1%), other uncommon mutations (median TTF = 4.5 mo; 95% CI: 2.9-9.7; ORR = 65.2%), and some exon 20 insertions (median TTF = 4.2 mo; 95% CI: 2.8-5.3; ORR = 24.3%). The median duration of response for major uncommon mutations, compound mutations, other uncommon mutations, and some exon 20 insertions was 17.1, 16.6, 9.0, and 11.9 months, respectively. Activity of afatinib was also observed in EGFR TKI-pretreated patients (n = 378). A searchable database of these outcomes by individual genotype was generated. CONCLUSIONS: Afatinib has clinical activity in NSCLC against major uncommon and compound EGFR mutations. It also has broad activity against other uncommon EGFR mutations and some exon 20 insertions. The data support the use of afatinib in these settings.
INTRODUCTION: Limited clinical data are available regarding the efficacy of EGFR tyrosine kinase inhibitors (EGFR TKIs) in patients with NSCLC harboring uncommon EGFR mutations. This pooled analysis assessed the activity of afatinib in 693 patients with tumors harboring uncommon EGFR mutations treated in randomized clinical trials, compassionate-use and expanded-access programs, phase IIIb trials, noninterventional trials, and case series or studies. METHODS:Patients had uncommon EGFR mutations, which were categorized as follows: (1) T790M; (2) exon 20 insertions; (3) "major" uncommon mutations (G719X, L861Q, and S768I, with or without any other mutation except T790M or an exon 20 insertion); (4) compound mutations; and (5) other uncommon mutations. Key end points were overall response rate (ORR), duration of response, and time to treatment failure (TTF). RESULTS: In EGFR TKI-naive patients (n = 315), afatinib demonstrated activity against major uncommon mutations (median TTF = 10.8 mo; 95% confidence interval [CI]: 8.1-16.6; ORR = 60.0%), compound mutations (median TTF = 14.7 mo; 95% CI: 6.8-18.5; ORR = 77.1%), other uncommon mutations (median TTF = 4.5 mo; 95% CI: 2.9-9.7; ORR = 65.2%), and some exon 20 insertions (median TTF = 4.2 mo; 95% CI: 2.8-5.3; ORR = 24.3%). The median duration of response for major uncommon mutations, compound mutations, other uncommon mutations, and some exon 20 insertions was 17.1, 16.6, 9.0, and 11.9 months, respectively. Activity of afatinib was also observed in EGFR TKI-pretreated patients (n = 378). A searchable database of these outcomes by individual genotype was generated. CONCLUSIONS:Afatinib has clinical activity in NSCLC against major uncommon and compound EGFR mutations. It also has broad activity against other uncommon EGFR mutations and some exon 20 insertions. The data support the use of afatinib in these settings.
Authors: James Chih-Hsin Yang; Martin Schuler; Sanjay Popat; Satoru Miura; Keunchil Park; Antonio Passaro; Filippo De Marinis; Flavio Solca; Angela Märten; Edward S Kim Journal: Front Oncol Date: 2022-04-28 Impact factor: 5.738
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Authors: Antonio Passaro; Filippo de Marinis; Hai-Yan Tu; Konstantin K Laktionov; Jifeng Feng; Artem Poltoratskiy; Jun Zhao; Eng Huat Tan; Maya Gottfried; Victor Lee; Dariusz Kowalski; Cheng Ta Yang; B J Srinivasa; Laura Clementi; Tejaswini Jalikop; Dennis Chin Lun Huang; Agnieszka Cseh; Keunchil Park; Yi-Long Wu Journal: Front Oncol Date: 2021-07-09 Impact factor: 6.244