S S Ramalingam1, K O'Byrne2, M Boyer3, T Mok4, P A Jänne5, H Zhang6, J Liang6, I Taylor6, E I Sbar6, L Paz-Ares7. 1. Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, USA suresh.ramalingam@emory.edu. 2. Department of Oncology, Princess Alexandra Hospital, Woolloongabba, Brisbane. 3. Department of Oncology, Chris O'Brien Lifehouse, Camperdown, Sydney, Australia. 4. Clinical Oncology, The Chinese University of Hong Kong, Shatin, Hong Kong. 5. Dana Farber Cancer Institute, Boston. 6. Pfizer Oncology, New York, USA. 7. Department of Oncology, Doce de Octubre University Hospital & CNIO, Madrid, Spain.
Abstract
BACKGROUND: The irreversible epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in NSCLC patients with activating EGFR mutations, but it is unknown if they are superior to the reversible inhibitors. Dacomitinib is an oral, small-molecule irreversible inhibitor of all enzymatically active HER family tyrosine kinases. METHODS: The ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067) studies randomized patients with locally advanced/metastatic NSCLC following progression with one or two prior chemotherapy regimens to dacomitinib or erlotinib. EGFR mutation testing was performed centrally on archived tumor samples. We pooled patients with exon 19 deletion and L858R EGFR mutations from both studies to compare the efficacy of dacomitinib to erlotinib. RESULTS: One hundred twenty-one patients with any EGFR mutation were enrolled; 101 had activating mutations in exon 19 or 21. For patients with exon19/21 mutations, the median progression-free survival was 14.6 months [95% confidence interval (CI) 9.0-18.2] with dacomitinib and 9.6 months (95% CI 7.4-12.7) with erlotinib [unstratified hazard ratio (HR) 0.717 (95% CI 0.458-1.124), two-sided log-rank, P = 0.146]. The median survival was 26.6 months (95% CI 21.6-41.5) with dacomitinib versus 23.2 months (95% CI 16.0-31.8) with erlotinib [unstratified HR 0.737 (95% CI 0.431-1.259), two-sided log-rank, P = 0.265]. Dacomitinib was associated with a higher incidence of diarrhea and mucositis in both studies compared with erlotinib. CONCLUSIONS: Dacomitinib is an active agent with comparable efficacy to erlotinib in the EGFR mutated patients. The subgroup with exon 19 deletion had favorable outcomes with dacomitinib. An ongoing phase III study will compare dacomitinib to gefitinib in first-line therapy of patients with NSCLC harboring common activating EGFR mutations (ARCHER 1050; NCT01774721). CLINICAL TRIALS NUMBER: ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067).
BACKGROUND: The irreversible epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in NSCLC patients with activating EGFR mutations, but it is unknown if they are superior to the reversible inhibitors. Dacomitinib is an oral, small-molecule irreversible inhibitor of all enzymatically active HER family tyrosine kinases. METHODS: The ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067) studies randomized patients with locally advanced/metastatic NSCLC following progression with one or two prior chemotherapy regimens to dacomitinib or erlotinib. EGFR mutation testing was performed centrally on archived tumor samples. We pooled patients with exon 19 deletion and L858R EGFR mutations from both studies to compare the efficacy of dacomitinib to erlotinib. RESULTS: One hundred twenty-one patients with any EGFR mutation were enrolled; 101 had activating mutations in exon 19 or 21. For patients with exon19/21 mutations, the median progression-free survival was 14.6 months [95% confidence interval (CI) 9.0-18.2] with dacomitinib and 9.6 months (95% CI 7.4-12.7) with erlotinib [unstratified hazard ratio (HR) 0.717 (95% CI 0.458-1.124), two-sided log-rank, P = 0.146]. The median survival was 26.6 months (95% CI 21.6-41.5) with dacomitinib versus 23.2 months (95% CI 16.0-31.8) with erlotinib [unstratified HR 0.737 (95% CI 0.431-1.259), two-sided log-rank, P = 0.265]. Dacomitinib was associated with a higher incidence of diarrhea and mucositis in both studies compared with erlotinib. CONCLUSIONS: Dacomitinib is an active agent with comparable efficacy to erlotinib in the EGFR mutated patients. The subgroup with exon 19 deletion had favorable outcomes with dacomitinib. An ongoing phase III study will compare dacomitinib to gefitinib in first-line therapy of patients with NSCLC harboring common activating EGFR mutations (ARCHER 1050; NCT01774721). CLINICAL TRIALS NUMBER: ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067).
Authors: Pawel Krawczyk; Dariusz M Kowalski; Rodryg Ramlau; Ewa Kalinka-Warzocha; Kinga Winiarczyk; Katarzyna Stencel; Tomasz Powrózek; Katarzyna Reszka; Kamila Wojas-Krawczyk; Maciej Bryl; Magdalena Wójcik-Superczyńska; Maciej Głogowski; Aleksander Barinow-Wojewódzki; Janusz Milanowski; Maciej Krzakowski Journal: Oncol Lett Date: 2017-04-03 Impact factor: 2.967
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