Final Overall Survival and Other Efficacy and Safety Results From ASCEND-3: Phase II Study of Ceritinib in ALKi-Naive Patients With ALK-Rearranged NSCLC

Makoto Nishio, Enriqueta Felip, Sergey Orlov, Keunchil Park, Chong Jen Yu, Chun Ming Tsai, Manuel Cobo, Mark McKeage, Wu Chou Su, Tony Mok, Giorgio V. Scagliotti, David R. Spigel, Kalyanee Viraswami-Appanna, Zhe Chen, Vanessa Q. Passos, Alice T. Shaw

研究成果: Article

摘要

Introduction: The phase II, single-arm ASCEND-3 study assessed the efficacy and safety of ceritinib in anaplastic lymphoma kinase (ALK) inhibitor (ALKi)–naive patients with ALK-rearranged NSCLC who had received at least three previous lines of chemotherapy. Here, we report the final efficacy and safety results. Methods: Eligible patients (including those with asymptomatic or neurologically stable brain metastases) received oral ceritinib (750 mg/day, fasted). The primary end point was investigator-assessed overall response rate (ORR). Secondary end points were Blinded Independent Review Committee–assessed ORR; investigator- and Blinded Independent Review Committee–assessed overall intracranial response rate, duration of response, time to response, disease control rate, and progression-free survival (PFS); overall survival (OS); and safety. Exploratory end points included patient-reported outcomes. Results: Of the 124 patients enrolled, 122 (98.4%) had received previous antineoplastic medications (31 patients [25.0%] received at least three regimens), and 49 (39.5%) had baseline brain metastases. The median follow-up time (data cutoff: January 22, 2018) was 52.1 (range, 48.4–60.1) months. The investigator-assessed ORR was 67.7% (95% confidence interval [CI]: 58.8–75.9), and the median PFS was 16.6 months (95% CI: 11.0–23.2). The median OS was 51.3 months (95% CI: 42.7–55.3). Most common adverse events (all grades, ≥60% of patients, all-causality) were diarrhea (85.5%), nausea (78.2%), and vomiting (71.8%). Overall, 18 patients (14.5%) had an adverse event leading to treatment discontinuation. Health-related quality of life was maintained during ceritinib treatment. Conclusions: Ceritinib exhibited prolonged and clinically meaningful OS, PFS, and duration of response in chemotherapy-pretreated (at least three lines), ALKi-naive patients with ALK+ NSCLC. The safety profile was consistent with that reported in previous studies.

原文English
期刊Journal of Thoracic Oncology
DOIs
出版狀態Accepted/In press - 2020 一月 1

    指紋

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

引用此

Nishio, M., Felip, E., Orlov, S., Park, K., Yu, C. J., Tsai, C. M., Cobo, M., McKeage, M., Su, W. C., Mok, T., Scagliotti, G. V., Spigel, D. R., Viraswami-Appanna, K., Chen, Z., Passos, V. Q., & Shaw, A. T. (認可的出版社/出版中). Final Overall Survival and Other Efficacy and Safety Results From ASCEND-3: Phase II Study of Ceritinib in ALKi-Naive Patients With ALK-Rearranged NSCLC. Journal of Thoracic Oncology. https://doi.org/10.1016/j.jtho.2019.11.006