Erlotinib for Non-Small Cell Lung Cancer with Leptomeningeal Metastases: A Phase II Study (LOGIK1101)
| Autor: | Takeshi Kitazaki, Takashi Seto, Noriyuki Ebi, Taishi Harada, Takeharu Yamanaka, Kenji Sugio, Yoshimasa Shiraishi, Daisuke Himeji, Mitsuhiro Takenoyama, Akinobu Hamada, Takayuki Shimose, Kaname Nosaki |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.medical_specialty Lung Neoplasms Phases of clinical research Gastroenterology 03 medical and health sciences T790M Erlotinib Hydrochloride 0302 clinical medicine Internal medicine Carcinoma Non-Small-Cell Lung medicine Carcinoma Humans Epidermal growth factor receptor Lung cancer Prospective cohort study Protein Kinase Inhibitors biology business.industry Clinical Trial Results medicine.disease respiratory tract diseases ErbB Receptors 030104 developmental biology Oncology 030220 oncology & carcinogenesis Mutation biology.protein Quality of Life Cerebrospinal fluid penetration Erlotinib business medicine.drug |
| Zdroj: | Oncologist |
| ISSN: | 1549-490X |
| Popis: | Lessons Learned This phase II trial evaluated the efficacy of erlotinib for patients with non-small cell lung cancer with leptomeningeal metastasis. The 17 cerebrospinal fluid specimens that were available for epidermal growth factor receptor mutation analysis were all negative for the resistance-conferring T790M mutation. The cytological objective clearance rate was 30.0% (95% confidence interval: 11.9%–54.3%). The median time to progression was 2.2 months. The rate of cerebrospinal fluid penetration among these patients was equivalent to those in previous reports regarding leptomeningeal metastasis. Background Leptomeningeal metastases (LM) occur in approximately 5% of patients with non-small cell lung cancer (NSCLC) and are associated with a poor prognosis. However, no prospective study has identified an active chemotherapeutic drug in this setting. Methods Patients were considered eligible to receive erlotinib if they had NSCLC with cytologically confirmed LM. The objective cytological clearance rate, time to LM progression (TTP), overall survival (OS), quality of life outcomes, and pharmacokinetics were analyzed. This study was closed because of slow accrual at 21 of the intended 32 patients (66%). Results Between December 2011 and May 2015, 21 patients (17 with activating epidermal growth factor receptor [EGFR] mutations) were enrolled. The 17 cerebrospinal fluid specimens available were all negative for the T790M mutation, which confers erlotinib resistance. The clearance rate was 30.0% (95% confidence interval [CI]: 11.9%–54.3%), the median TTP was 2.2 months, and the median OS was 3.4 months. Significantly longer TTP and OS times were observed in patients with mutant EGFR (p = .0113 and p < .0054, respectively). The mean cerebrospinal fluid penetration rate was 3.31% ± 0.77%. There was a good correlation between plasma and cerebrospinal fluid (CSF) concentrations, although there was no clear correlation between pharmacokinetic parameters and clinical outcome. Conclusion Erlotinib was active for LM and may be a treatment option for patients with EGFR-mutated NSCLC and LM. |
| Databáze: | OpenAIRE |
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