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J Clin Oncol. 2016 Dec;34(34):4079-4085. Epub 2016 Oct 31.

Pooled Analysis of CNS Response to Alectinib in Two Studies of Pretreated Patients With ALK-Positive Non-Small-Cell Lung Cancer.

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Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Alice T. Shaw, Massachusetts General Hospital; Leena Gandhi, Dana-Farber Cancer Institute, Boston, MA; Ramaswamy Govindan, Washington University School of Medicine, St Louis, MO; Mark A. Socinski, University of Pittsburgh, Pittsburgh, PA; D. Ross Camidge, University of Colorado Cancer Center, Denver, CO; Alberto Chiappori, Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Sai-Hong Ignatius Ou, University of California at Irvine, Orange, CA; Luigi De Petris, Karolinska Institutet, Stockholm, Sweden; Dong-Wan Kim, Seoul National University Hospital, Seoul; Ji-Youn Han, Lung Cancer Centre, National Cancer Centre, Goyang, South Korea; Denis L. Moro-Sibilot, Service de Pneumologie; Michael Duruisseaux, Centre Hospitalier Universitaire de Grenoble, Grenoble; Eric Dansin, Centre Oscar Lambret, Lille, France; Lucio Crino, Santa Maria della Misericordia Hospital, Perugia; Tommaso De Pas, European Institute of Oncology, Milan, Italy; Antje Tessmer, Evangelische Lungenklinik Berlin, Berlin, Germany; James Chih-Hsin Yang, Graduate Institute of Oncology and Cancer Research Centre, National Taiwan University, Taipei, Taiwan; and Walter Bordogna, Sophie Golding, and Ali Zeaiter, F. Hoffmann-La Roche, Basel, Switzerland.


Purpose Alectinib has shown activity in the CNS in phase I and II studies. To further evaluate this activity, we pooled efficacy and safety data from two single-arm phase II studies (NP28761 and NP28673; identifiers: NCT01871805 and NCT01801111, respectively) in patients with ALK-positive non-small-cell lung cancer (NSCLC). Patients and Methods Both studies included patients with ALK-positive NSCLC who had previously received crizotinib; all patients received alectinib 600 mg twice per day. The primary end point in both studies was independent review committee (IRC)-assessed objective response rate (ORR; by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Additional end points (all by IRC) included CNS ORR (CORR), CNS disease control rate (CDCR), and CNS duration of response (CDOR). Results One hundred thirty-six patients had baseline CNS metastases (60% of the overall study populations); 50 patients (37%) had measurable CNS disease at baseline. Ninety-five patients (70%) had prior CNS radiotherapy; 55 patients completed the CNS radiotherapy more than 6 months before starting alectinib. Median follow-up time was 12.4 months (range, 0.9 to 19.7 months). For patients with baseline measurable CNS disease, IRC CORR was 64.0% (95% CI, 49.2% to 77.1%), CDCR was 90.0% (95% CI, 78.2% to 96.7%), and median CDOR was 10.8 months (95% CI, 7.6 to 14.1 months). For patients with measurable and/or nonmeasurable baseline CNS disease, IRC CORR was 42.6% (95% CI, 34.2% to 51.4%), CDCR was 85.3% (95% CI, 78.2% to 90.8%), and median CDOR was 11.1 months (95% CI, 10.3 months to not evaluable). CORR was 35.8% (95% CI, 26.2% to 46.3%) for patients with prior radiotherapy (n = 95) and 58.5% (95% CI, 42.1% to 73.7%) for patients without prior radiotherapy (n = 41). As previously reported, alectinib was well tolerated, regardless of baseline CNS disease. Conclusion Alectinib showed good efficacy against CNS metastases, in addition to systemic activity, in crizotinib-refractory ALK-positive NSCLC.

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