Alectinib in crizotinib-refractory alk-rearranged non-small-cell lung cancer: A phase II global study

Sai Hong Ignatius Ou, Jin Seok Ahn, Luigi De Petris, Ramaswamy Govindan, James Chih Hsin Yang, Brett Hughes, Hervé Lena, Denis Moro-Sibilot, Alessandra Bearz, Santiago Viteri Ramirez, Tarek Mekhail, Alexander Spira, Walter Bordogna, Bogdana Balas, Peter N. Morcos, Annabelle Monnet, Ali Zeaiter, Dong Wan Kim

Research output: Contribution to journalArticle

Abstract

Purpose: Crizotinib confers improved progression-free survival compared with chemotherapy in anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC), but progression invariably occurs. We investigated the efficacy and safety of alectinib, a potent and selective ALK inhibitor with excellent CNS penetration, in patients with crizotinib-refractory ALK-positive NSCLC. Patients and Methods: Alectinib 600 mg was administered orally twice daily. The primary end point was objective response rate (ORR) by central independent review committee (IRC). Results: Of the 138 patients treated, 84 patients (61%) had CNS metastases at baseline, and 122 were response evaluable (RE) by IRC. ORR by IRC was 50% (95% CI, 41% to 59%), and the median duration of response (DOR) was 11.2 months (95% CI, 9.6 months to not reached). In 96 patients (79%) previously treated with chemotherapy, the ORR was 45% (95% CI, 35% to 55%). Median IRC-assessed progression-free survival for all 138 patients was 8.9 months (95% CI, 5.6 to 11.3 months). CNS disease control rate was 83% (95% CI, 74% to 91%), and the median CNS DOR was 10.3 months (95% CI, 7.6 to 11.2 months). CNS ORR in 35 patients with baseline measurable CNS lesions was 57% (95% CI, 39% to 74%). Of the 23 patients with baseline CNS metastases (measurable or nonmeasurable) and no prior radiation, 10 (43%) had a complete CNS response. At 12 months, the cumulative CNS progression rate (24.8%) was lower than the cumulative non-CNS progression rate (33.2%) for all patients. Common adverse events were constipation (33%), fatigue (26%), and peripheral edema (25%); most were grade 1 to 2. Conclusion: Alectinib is highly active and well tolerated in patients with advanced, crizotinib-refractory ALK-positive NSCLC, including those with CNS metastases.

Original languageEnglish (US)
Pages (from-to)661-668
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number7
DOIs
Publication statusPublished - Mar 1 2016
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ou, S. H. I., Ahn, J. S., De Petris, L., Govindan, R., Yang, J. C. H., Hughes, B., ... Kim, D. W. (2016). Alectinib in crizotinib-refractory alk-rearranged non-small-cell lung cancer: A phase II global study. Journal of Clinical Oncology, 34(7), 661-668. https://doi.org/10.1200/JCO.2015.63.9443