Efficacy of Brigatinib in Patients With Advanced ALK-Positive NSCLC Who Progressed on Alectinib or Ceritinib: ALK in Lung Cancer Trial of brigAtinib-2 (ALTA-2)
| Autor: | Sai-Hong Ignatius, Ou, Makoto, Nishio, Myung-Ju, Ahn, Tony, Mok, Fabrice, Barlesi, Caicun, Zhou, Enriqueta, Felip, Filippo, de Marinis, Sang-We, Kim, Maurice, Pérol, Geoffrey, Liu, Maria Rita, Migliorino, Dong-Wan, Kim, Silvia, Novello, Alessandra, Bearz, Pilar, Garrido, Julien, Mazieres, Alessandro, Morabito, Huamao M, Lin, Hui, Yang, Huifeng, Niu, Pingkuan, Zhang, Edward S, Kim |
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| Přispěvatelé: | Institut Català de la Salut, [Ou SI] Department of Medicine, Division of Hematology-Oncology, Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California. [Nishio M] Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. [Ahn MJ] Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. [Mok T] State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China. [Barlesi F] Aix-Marseille University, CNRS, INSERM, CRCM, Marseille, France. Multidisciplinary Oncology & Therapeutic Innovations Department, Gustave Roussy Cancer Campus, Villejuif, France. [Zhou C] Shanghai Pulmonary Hospital, Shanghai, People’s Republic of China. [Felip E] Servei d’Oncologia Mèdica, Vall d'Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Rok vydání: | 2022 |
| Předmět: |
Pulmonary and Respiratory Medicine
Lung Neoplasms Otros calificadores::/uso terapéutico [Otros calificadores] Carbazoles Medicaments antineoplàstics - Ús terapèutic Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS] diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma Bronchogenic::Carcinoma Non-Small-Cell Lung [DISEASES] 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] Other subheadings::Other subheadings::/drug therapy [Other subheadings] Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] Oncology Carcinoma Non-Small-Cell Lung Avaluació de resultats (Assistència sanitària) Humans Anaplastic Lymphoma Kinase Other subheadings::/therapeutic use [Other subheadings] Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS] Pulmons - Càncer - Tractament Protein Kinase Inhibitors |
| Zdroj: | Scientia |
| ISSN: | 1556-0864 |
| DOI: | 10.1016/j.jtho.2022.08.018 |
| Popis: | Circulating tumor DNA; Non–small cell lung cancer; Tumor biomarker ADN tumoral circulante; Cáncer de pulmón de células no pequeñas; Biomarcador tumoral ADN tumoral circulant; Càncer de pulmó de cèl·lules no petites; Biomarcador tumoral Introduction Brigatinib is a potent next-generation ALK tyrosine kinase inhibitor approved for treatment-naive and crizotinib-refractory advanced ALK-positive (ALK+) NSCLC. We evaluated brigatinib after other next-generation ALK tyrosine kinase inhibitors. Methods In this single-arm, phase 2, ALK in Lung Cancer Trial of brigAtinib-2 (NCT03535740), patients with advanced ALK+ NSCLC whose disease progressed on alectinib or ceritinib received brigatinib 180 mg once daily (after 7-d 90-mg lead-in). Primary end point was independent review committee (IRC)-assessed overall response rate (ORR). Circulating tumor DNA (ctDNA) was analyzed. Results Among 103 patients (data cutoff: September 30, 2020; median follow-up [range]: 10.8 [0.5–17.7] mo), confirmed IRC-ORR was 26.2% (95% confidence interval [CI]: 18.0–35.8), median duration of response, 6.3 months (95% CI: 5.6–not reached), and median progression-free survival (mPFS), 3.8 months (95% CI: 3.5–5.8). mPFS was 1.9 months (95% CI: 1.8–3.7) in patients with ctDNA-detectable baseline ALK fusion (n = 64). Among 86 patients who progressed on alectinib, IRC-ORR was 29.1% (95% CI: 19.8–39.9); mPFS was 3.8 months (95% CI: 1.9–5.4). Resistance mutations were present in 33.3% (26 of 78) of baseline ctDNA; 54% (14 of 26) of mutations were G1202R; 52% (33 of 64) of patients with detectable ALK fusion had EML4-ALK variant 3. Most common all-grade treatment-related adverse events were increased creatine phosphokinase (32%) and diarrhea (27%). The mean dose intensity of brigatinib (180 mg once daily) was 85.9%. Conclusions In ALK in Lung Cancer Trial of brigAtinib-2, brigatinib was found to have a limited activity in patients with ALK+ NSCLC post-ceritinib or post-alectinib therapy. mPFS was longer with brigatinib in patients without baseline detectable plasma ALK fusion. |
| Databáze: | OpenAIRE |
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