Progression-Free and Overall Survival in ALK-Positive NSCLC Patients Treated with Sequential Crizotinib and Ceritinib
| Autor: | Katherine Schultz, Gianluca Spitaleri, Filippo de Marinis, Benjamin Solomon, Beow Y. Yeap, Daniel Shao-Weng Tan, Alice T. Shaw, Tomasso De Pas, Chiara Lazzari, Luc Friboulet, Jeffrey A. Engelman, Justin F. Gainor, Aziah Ahmad |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Oncology
Adult Male Cancer Research medicine.medical_specialty Lung Neoplasms Pyridines medicine.medical_treatment Biopsy Drug Administration Schedule Article Young Adult Crizotinib hemic and lymphatic diseases Internal medicine Carcinoma Non-Small-Cell Lung medicine Carcinoma Anaplastic lymphoma kinase Humans Anaplastic Lymphoma Kinase Sulfones Survival analysis Aged Neoplasm Staging Chemotherapy Ceritinib business.industry Cancer Receptor Protein-Tyrosine Kinases Imatinib Middle Aged medicine.disease Survival Analysis Surgery Pyrimidines Treatment Outcome Mutation Pyrazoles Female business medicine.drug |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 21(12) |
| ISSN: | 1557-3265 |
| Popis: | Purpose: Anaplastic lymphoma kinase (ALK) rearrangements are important therapeutic targets in non–small cell lung cancer (NSCLC) that confer sensitivity to the ALK inhibitors crizotinib and ceritinib. To determine the outcome of sequential treatment with crizotinb and ceritinib, we retrospectively evaluated a cohort of ALK-positive patients treated with both agents. Experimental Design: We identified 73 ALK-positive NSCLC patients treated with crizotinib followed by ceritinib at four institutions. Medical records were reviewed to determine overall survival (OS) and progression-free survival (PFS) on crizotinib and ceritinib. Results: Among 73 ALK-positive patients, the median PFS (mPFS) on crizotinib was 8.2 months [95% confidence interval (CI), 7.4–10.6]. The median interval from crizotinib discontinuation to initiation of ceritinib was 25 days (range, 1–694). The mPFS on ceritinib was 7.8 months (6.5–9.1). Among 53 patients with no interval therapies between crizotinib and ceritinib, the mPFS on ceritinib was similar at 7.8 months (5.4–9.8). The median combined PFS for sequential treatment with crizotinib and ceritinib was 17.4 months (15.5–19.4). Among 23 patients who underwent post-crizotinib/pre-ceritinib biopsies, there was no difference in PFS on ceritinib between patients with or without ALK resistance mutations (mPFS 5.8 vs. 6.5 months, respectively; P = 0.510). In the overall study population, median OS was 49.4 months (35.5–63.1). Conclusions: Ceritinib has significant antitumor activity in ALK-positive NSCLC—even when crizotinib immediately precedes treatment with ceritinib (median combined PFS 17.0 months). Additional studies are necessary to further define the impact of specific ALK resistance mutations on duration of response to ceritinib. Clin Cancer Res; 21(12); 2745–52. ©2015 AACR. |
| Databáze: | OpenAIRE |
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