UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Medline ® Abstracts for References 48,49

of 'Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer'

48
TI
Clinical Experience With Crizotinib in Patients With Advanced ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastases.
AU
Costa DB, Shaw AT, Ou SH, Solomon BJ, Riely GJ, Ahn MJ, Zhou C, Shreeve SM, Selaru P, Polli A, Schnell P, Wilner KD, Wiltshire R, Camidge DR, CrinòL
SO
J Clin Oncol. 2015;33(17):1881. Epub 2015 Jan 26.
 
PURPOSE: Crizotinib is an oral kinase inhibitor approved for the treatment of ALK-rearranged non-small-cell lung cancer (NSCLC). The clinical benefits of crizotinib in patients with brain metastases have not been previously studied.
PATIENTS AND METHODS: Patients with advanced ALK-rearranged NSCLC enrolled onto clinical trial PROFILE 1005 or 1007 (randomly assigned to crizotinib) were included in this retrospective analysis. Patients with asymptomatic brain metastases (nontarget or target lesions) were allowed to enroll. Tumor assessments were evaluated every 6 weeks using RECIST (version 1.1).
RESULTS: At baseline, 31% of patients (275 of 888) had asymptomatic brain metastases; 109 had received no prior and 166 had received prior brain radiotherapy as treatment. Among patients with previously untreated asymptomatic brain metastases, the systemic disease control rate (DCR) at 12 weeks was 63% (95% CI, 54% to 72%), the intracranial DCR was 56% (95% CI, 46% to 66%), and the median intracranial time to progression (TTP) was 7 months (95% CI, 6.7 to 16.4). Among patients with previously treated brain metastases, the systemic DCR was 65% (95% CI, 57% to 72%), the intracranial DCR was 62% (95% CI, 54% to 70%), and the median intracranial TTP was 13.2 months (95% CI, 9.9 to not reached). Patients with systemic disease control were also likely to experience intracranial disease control at 12 weeks (correlation coefficient, 0.7652; P<.001). Among patients without baseline brain metastases who developed progressive disease (n = 253) after initiation of crizotinib, 20% were diagnosed with brain metastases.
CONCLUSION: Crizotinib was associated with systemic and intracranial disease control in patients with ALK-rearranged NSCLC who were ALK inhibitor naive and had brain metastases. However, progression of preexisting or development of new intracranial lesions while receiving therapy was a common manifestation of acquired resistance to crizotinib.
AD
Daniel B. Costa, Beth Israel Deaconess Medical Center, Harvard Medical School; Alice T. Shaw, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Sai-Hong I. Ou, Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Irvine; S. Martin Shreeve, Paulina Selaru, and Keith D. Wilner, Pfizer Oncology, La Jolla, CA; Benjamin J. Solomon, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Gregory J. Riely, Memorial Sloan-Kettering Cancer Center; Patrick Schnell, Pfizer Oncology, New York, NY; Myung-Ju Ahn, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea; Caicun Zhou, Shanghai Pulmonary Hospital, Shanghai, People's Republic of China; Anna Polli, Pfizer Oncology, Milan; Lucio Crinò, Perugia University Medical School, Perugia, Italy; Robin Wiltshire, Pfizer Oncology, Tadworth, United Kingdom; and D. Ross Camidge, University of Colorado Denver, Aurora, CO. dbcosta@bidmc.harvard.edu.
PMID
49
TI
Pooled Analysis of CNS Response to Alectinib in Two Studies of Pretreated Patients With ALK-Positive Non-Small-Cell Lung Cancer.
AU
Gadgeel SM, Shaw AT, Govindan R, Gandhi L, Socinski MA, Camidge DR, De Petris L, Kim DW, Chiappori A, Moro-Sibilot DL, Duruisseaux M, Crino L, De Pas T, Dansin E, Tessmer A, Yang JC, Han JY, Bordogna W, Golding S, Zeaiter A, Ou SI
SO
J Clin Oncol. 2016;34(34):4079. Epub 2016 Oct 31.
 
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; ClinicalTrials.gov identifiers: NCT01871805 and NCT01801111, respectively) inpatients 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.
AD
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
PMID