Olmutinib in T790M-positive non–small cell lung cancer after failure of first-line epidermal growth factor receptor-tyrosine kinase inhibitor therapy: A global, phase 2 study
| Autor: | Keunchil Park, Eunhye Baek, Yong Kek Pang, Jong Seok Lee, Chong-Jen Yu, Hyun Jin Kim, Enriqueta Felip, Young Su Noh, Ming-Fang Wu, Jin Hyoung Kang, Dong Wan Kim, Byoung Chul Cho, Dae Ho Lee, Ji Youn Han, Pasi A. Jӓnne |
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| Přispěvatelé: | Institut Català de la Salut, [Park K] Division of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. [Jӓnne PA] Lowe Center for Thoracic Oncology, The Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts. [Kim DW] Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. [Han JY] National Cancer Center, Goyang, Republic of Korea. [Wu MF] Chung Shan Medical University Hospital, Taichung, Taiwan. [Lee JS] Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. [Felip E] Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Cancer Research Lung Neoplasms Phases of clinical research T790M Gastroenterology Piperazines Circulating Tumor DNA Medicaments antineoplàstics non–small cell lung cancer tyrosine kinase inhibitor 0302 clinical medicine Carcinoma Non-Small-Cell Lung Clinical endpoint Treatment Failure 030212 general & internal medicine Epidermal growth factor receptor Aged 80 and over biology Brain Neoplasms Common Terminology Criteria for Adverse Events Middle Aged Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma Bronchogenic::Carcinoma Non-Small-Cell Lung [DISEASES] Diagnosis::Prognosis::Treatment Outcome::Progression-Free Survival [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] Progression-Free Survival ErbB Receptors Oncology 030220 oncology & carcinogenesis Original Article Female Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS] Adult medicine.medical_specialty olmutinib Prognosi diagnóstico::pronóstico::resultado del tratamiento::supervivencia libre de progresión [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Drug Administration Schedule Discipline 03 medical and health sciences Internal medicine Confidence Intervals medicine Humans Clinical Trials Adverse effect Lung cancer Protein Kinase Inhibitors Aged business.industry Cancer acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS] Original Articles neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas [ENFERMEDADES] medicine.disease Pyrimidines Mutation biology.protein epidermal growth factor receptor business Pulmons - Càncer - Tractament |
| Zdroj: | Scientia Cancer |
| Popis: | Background In this open‐label, international phase 2 study, the authors assessed the efficacy and safety of olmutinib in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) who had a confirmed T790M mutation and disease progression on previous epidermal growth factor receptor‐tyrosine kinase inhibitor therapy. Methods Patients aged ≥20 years received once‐daily oral olmutinib 800 mg continuously in 21‐day cycles. The primary endpoint was the objective response rate (patients who had a confirmed best overall response of a complete or partial response), assessed by central review. Secondary endpoints included the disease control rate, the duration of objective response, progression‐free survival, and overall survival. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Results Overall, 162 patients (median age, 63 years; women, >60%) were enrolled from 68 sites in 9 countries. At the time of database cutoff, 23.5% of enrolled patients remained on treatment. The median treatment duration was 6.5 months (range, 0.03‐21.68 months). Overall, 46.3% of patients (95% CI, 38.4%‐54.3%) had a confirmed objective response (all partial responses). The best overall response (the objective response rate regardless of confirmation) was 51.9% (84 patients; 95% CI, 43.9%‐59.8%). The confirmed disease control rate for all patients was 86.4% (95% CI, 80.2%‐91.3%). The median duration of objective response was 12.7 months (95% CI, 8.3‐15.4 months). Estimated median progression‐free survival was 9.4 months (95% CI, 6.9‐12.3 months), and estimated median overall survival was 19.7 months (95% CI, 15.1 months to not reached). All patients experienced treatment‐emergent adverse events, and 71.6% of patients had grade ≥3 treatment‐emergent adverse events. Conclusions Olmutinib has meaningful clinical activity and a manageable safety profile in patients with T790M‐positive non–small cell lung cancer who received previous epidermal growth factor receptor‐tyrosine kinase inhibitor therapy. Olmutinib (HM61713) is a third‐generation, mutation‐specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that targets mutant‐type EGFR and has minimal activity against wild‐type EGFR. This open‐label, international phase 2 study demonstrates the efficacy and safety of oral olmutinib 800 mg once daily in patients with locally advanced or metastatic non–small cell lung cancer who have a confirmed T790M mutation and disease progression on previous EGFR tyrosine kinase inhibitor therapy. |
| Databáze: | OpenAIRE |
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