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

Ou, Sai-Hong Ignatius, Ahn, Jin Seok, De Petris, Luigi, Govindan, Ramaswamy, Yang, James Chin-Hsin, Hughes, Brett, Lena, Herve, Moro-Sibilot, Denis, Bearz, Alessandra, Ramirez, Santiago Viteri, Mekhail, Tarek, Spira, Alexander, Bordogna, Walter, Balas, Bogdana, Morcos, Peter N., Monnet, Annabelle, Zeaiter, Ali and Kim, Dong-Wan (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. doi:10.1200/JCO.2015.63.9443

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Author Ou, Sai-Hong Ignatius
Ahn, Jin Seok
De Petris, Luigi
Govindan, Ramaswamy
Yang, James Chin-Hsin
Hughes, Brett
Lena, Herve
Moro-Sibilot, Denis
Bearz, Alessandra
Ramirez, Santiago Viteri
Mekhail, Tarek
Spira, Alexander
Bordogna, Walter
Balas, Bogdana
Morcos, Peter N.
Monnet, Annabelle
Zeaiter, Ali
Kim, Dong-Wan
Title Alectinib in crizotinib-refractory alk-rearranged non-small-cell lung cancer: a phase II global study
Journal name Journal of Clinical Oncology   Check publisher's open access policy
ISSN 1527-7755
Publication date 2016-03-01
Year available 2016
Sub-type Article (original research)
DOI 10.1200/JCO.2015.63.9443
Open Access Status File (Publisher version)
Volume 34
Issue 7
Start page 661
End page 668
Total pages 8
Place of publication Alexandria, VA United States
Publisher American Society of Clinical Oncology
Collection year 2017
Language eng
Formatted 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.
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Document type: Journal Article
Sub-type: Article (original research)
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