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Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study
Sai-Hong Ignatius Ou1, Jin Seok Ahn2, Luigi De Petris2
1Sai-Hong Ignatius Ou, University of California Irvine School of Medicine, Orange, CA; Jin Seok Ahn, Sungkyunkwan University School of Medicine; Luigi De Petris, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden; Ramaswamy Govindan, Washington University School of Medicine, St Louis, MO; James Chih-Hsin Yang, National Taiwan University, Taipei, Taiwan; Brett Hughes, The Prince Charles Hospital, Chermside, and University of Queensland, Queensland, Australia; Hervé Lena, Centre Hospitalier Universitaire de Rennes, Rennes; Denis Moro-Sibilot, Centre Hospitalier Universitaire de Grenoble, Institut National de la Santé et de la Recherche Médicale U823, Grenoble, France; Alessandra Bearz, National Cancer Institute, Aviano, Italy; Santiago Viteri Ramirez, Quiron-Dexeus University Hospital, Barcelona, Spain; Tarek Mekhail, Florida Hospital Cancer Institute, Orlando, FL; Alexander Spira, Virginia Cancer Specialists, Fairfax, VA; and Walter Bordogna, Bogdana Balas, Peter N. Morcos, Annabelle Monnet, and Ali Zeaiter, F. Hoffmann-La Roche, Basel, Switzerland; Dong-Wan Kim, Seoul National University Hospital, Seoul, South Korea. ignatius.ou@uci.edu.
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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