Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study
The phase III ALEX study in patients with treatment-naive advanced anaplastic lymphoma kinase mutation-positive (ALK+) non-small-cell lung cancer (NSCLC) met its primary end point of improved progression-free survival (PFS) with alectinib versus crizotinib. Here, we present detailed central nervous...
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| Veröffentlicht in: | Annals of oncology 2018-11, Vol.29 (11), p.2214-2222 |
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| creator | Gadgeel, S. Peters, S. Mok, T. Shaw, A.T. Kim, D.W. Ou, S.I. Pérol, M. Wrona, A. Novello, S. Rosell, R. Zeaiter, A. Liu, T. Nüesch, E. Balas, B. Camidge, D.R. |
| description | The phase III ALEX study in patients with treatment-naive advanced anaplastic lymphoma kinase mutation-positive (ALK+) non-small-cell lung cancer (NSCLC) met its primary end point of improved progression-free survival (PFS) with alectinib versus crizotinib. Here, we present detailed central nervous system (CNS) efficacy data from ALEX.
Overall, 303 patients aged ≥18 years underwent 1:1 randomization to receive twice-daily doses of alectinib 600 mg or crizotinib 250 mg. Brain imaging was conducted in all patients at baseline and every subsequent 8 weeks. End points (analyzed by subgroup: patients with/without baseline CNS metastases; patients with/without prior radiotherapy) included PFS, CNS objective response rate (ORR), and time to CNS progression.
In total, 122 patients had Independent Review Committee-assessed baseline CNS metastases (alectinib,n = 64; crizotinib,n = 58), 43 had measurable lesions (alectinib,n = 21; crizotinib,n = 22), and 46 had received prior radiotherapy (alectinib,n = 25; crizotinib,n = 21). Investigator-assessed PFS with alectinib was consistent between patients with baseline CNS metastases [hazard ratio (HR) 0.40, 95% confidence interval (CI): 0.25–0.64] and those without (HR 0.51, 95% CI: 0.33–0.80,P interaction = 0.36). Similar results were seen in patients regardless of prior radiotherapy. Time to CNS progression was significantly longer with alectinib versus crizotinib and comparable between patients with and without baseline CNS metastases (P < 0.0001). CNS ORR was 85.7% with alectinib versus 71.4% with crizotinib in patients who received prior radiotherapy and 78.6% versus 40.0%, respectively, in those who had not.
Alectinib demonstrated superior CNS activity and significantly delayed CNS progression versus crizotinib in patients with previously untreated, advancedALK+ NSCLC, irrespective of prior CNS disease or radiotherapy.
ClinicalTrials.gov NCT02075840 |
| doi_str_mv | 10.1093/annonc/mdy405 |
| format | Article |
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Overall, 303 patients aged ≥18 years underwent 1:1 randomization to receive twice-daily doses of alectinib 600 mg or crizotinib 250 mg. Brain imaging was conducted in all patients at baseline and every subsequent 8 weeks. End points (analyzed by subgroup: patients with/without baseline CNS metastases; patients with/without prior radiotherapy) included PFS, CNS objective response rate (ORR), and time to CNS progression.
In total, 122 patients had Independent Review Committee-assessed baseline CNS metastases (alectinib,n = 64; crizotinib,n = 58), 43 had measurable lesions (alectinib,n = 21; crizotinib,n = 22), and 46 had received prior radiotherapy (alectinib,n = 25; crizotinib,n = 21). Investigator-assessed PFS with alectinib was consistent between patients with baseline CNS metastases [hazard ratio (HR) 0.40, 95% confidence interval (CI): 0.25–0.64] and those without (HR 0.51, 95% CI: 0.33–0.80,P interaction = 0.36). Similar results were seen in patients regardless of prior radiotherapy. Time to CNS progression was significantly longer with alectinib versus crizotinib and comparable between patients with and without baseline CNS metastases (P < 0.0001). CNS ORR was 85.7% with alectinib versus 71.4% with crizotinib in patients who received prior radiotherapy and 78.6% versus 40.0%, respectively, in those who had not.
Alectinib demonstrated superior CNS activity and significantly delayed CNS progression versus crizotinib in patients with previously untreated, advancedALK+ NSCLC, irrespective of prior CNS disease or radiotherapy.
ClinicalTrials.gov NCT02075840</description><identifier>ISSN: 0923-7534</identifier><identifier>EISSN: 1569-8041</identifier><identifier>DOI: 10.1093/annonc/mdy405</identifier><identifier>PMID: 30215676</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; Aged ; Aged, 80 and over ; alectinib ; ALK-positive ; Anaplastic Lymphoma Kinase - antagonists & inhibitors ; Anaplastic Lymphoma Kinase - genetics ; Brain - diagnostic imaging ; Brain - drug effects ; Brain - radiation effects ; Brain Neoplasms - diagnostic imaging ; Brain Neoplasms - genetics ; Brain Neoplasms - secondary ; Brain Neoplasms - therapy ; Carbazoles - pharmacology ; Carbazoles - therapeutic use ; Carcinoma, Non-Small-Cell Lung - diagnostic imaging ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - secondary ; Carcinoma, Non-Small-Cell Lung - therapy ; Chemoradiotherapy - methods ; CNS ; Crizotinib - pharmacology ; Crizotinib - therapeutic use ; Disease Progression ; Female ; Humans ; Lung - diagnostic imaging ; Lung - drug effects ; Lung - radiation effects ; Lung Neoplasms - diagnostic imaging ; Lung Neoplasms - genetics ; Lung Neoplasms - pathology ; Lung Neoplasms - therapy ; Magnetic Resonance Imaging ; Male ; Middle Aged ; NSCLC ; Original articles ; Piperidines - pharmacology ; Piperidines - therapeutic use ; Treatment Outcome ; Tumor Burden - drug effects ; Tumor Burden - radiation effects ; Young Adult</subject><ispartof>Annals of oncology, 2018-11, Vol.29 (11), p.2214-2222</ispartof><rights>2018 THE AUTHORS</rights><rights>The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c534t-30737372661b52db7c44a6df18782ed0f9181e3c67fc0cfac683b1ee12f72f493</citedby><cites>FETCH-LOGICAL-c534t-30737372661b52db7c44a6df18782ed0f9181e3c67fc0cfac683b1ee12f72f493</cites><orcidid>0000-0002-0412-7143</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30215676$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gadgeel, S.</creatorcontrib><creatorcontrib>Peters, S.</creatorcontrib><creatorcontrib>Mok, T.</creatorcontrib><creatorcontrib>Shaw, A.T.</creatorcontrib><creatorcontrib>Kim, D.W.</creatorcontrib><creatorcontrib>Ou, S.I.</creatorcontrib><creatorcontrib>Pérol, M.</creatorcontrib><creatorcontrib>Wrona, A.</creatorcontrib><creatorcontrib>Novello, S.</creatorcontrib><creatorcontrib>Rosell, R.</creatorcontrib><creatorcontrib>Zeaiter, A.</creatorcontrib><creatorcontrib>Liu, T.</creatorcontrib><creatorcontrib>Nüesch, E.</creatorcontrib><creatorcontrib>Balas, B.</creatorcontrib><creatorcontrib>Camidge, D.R.</creatorcontrib><title>Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study</title><title>Annals of oncology</title><addtitle>Ann Oncol</addtitle><description>The phase III ALEX study in patients with treatment-naive advanced anaplastic lymphoma kinase mutation-positive (ALK+) non-small-cell lung cancer (NSCLC) met its primary end point of improved progression-free survival (PFS) with alectinib versus crizotinib. Here, we present detailed central nervous system (CNS) efficacy data from ALEX.
Overall, 303 patients aged ≥18 years underwent 1:1 randomization to receive twice-daily doses of alectinib 600 mg or crizotinib 250 mg. Brain imaging was conducted in all patients at baseline and every subsequent 8 weeks. End points (analyzed by subgroup: patients with/without baseline CNS metastases; patients with/without prior radiotherapy) included PFS, CNS objective response rate (ORR), and time to CNS progression.
In total, 122 patients had Independent Review Committee-assessed baseline CNS metastases (alectinib,n = 64; crizotinib,n = 58), 43 had measurable lesions (alectinib,n = 21; crizotinib,n = 22), and 46 had received prior radiotherapy (alectinib,n = 25; crizotinib,n = 21). Investigator-assessed PFS with alectinib was consistent between patients with baseline CNS metastases [hazard ratio (HR) 0.40, 95% confidence interval (CI): 0.25–0.64] and those without (HR 0.51, 95% CI: 0.33–0.80,P interaction = 0.36). Similar results were seen in patients regardless of prior radiotherapy. Time to CNS progression was significantly longer with alectinib versus crizotinib and comparable between patients with and without baseline CNS metastases (P < 0.0001). CNS ORR was 85.7% with alectinib versus 71.4% with crizotinib in patients who received prior radiotherapy and 78.6% versus 40.0%, respectively, in those who had not.
Alectinib demonstrated superior CNS activity and significantly delayed CNS progression versus crizotinib in patients with previously untreated, advancedALK+ NSCLC, irrespective of prior CNS disease or radiotherapy.
ClinicalTrials.gov NCT02075840</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>alectinib</subject><subject>ALK-positive</subject><subject>Anaplastic Lymphoma Kinase - antagonists & inhibitors</subject><subject>Anaplastic Lymphoma Kinase - genetics</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - drug effects</subject><subject>Brain - radiation effects</subject><subject>Brain Neoplasms - diagnostic imaging</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - secondary</subject><subject>Brain Neoplasms - therapy</subject><subject>Carbazoles - pharmacology</subject><subject>Carbazoles - therapeutic use</subject><subject>Carcinoma, Non-Small-Cell Lung - diagnostic imaging</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - secondary</subject><subject>Carcinoma, Non-Small-Cell Lung - therapy</subject><subject>Chemoradiotherapy - methods</subject><subject>CNS</subject><subject>Crizotinib - pharmacology</subject><subject>Crizotinib - therapeutic use</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Humans</subject><subject>Lung - diagnostic imaging</subject><subject>Lung - drug effects</subject><subject>Lung - radiation effects</subject><subject>Lung Neoplasms - diagnostic imaging</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - therapy</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Middle Aged</subject><subject>NSCLC</subject><subject>Original articles</subject><subject>Piperidines - pharmacology</subject><subject>Piperidines - therapeutic use</subject><subject>Treatment Outcome</subject><subject>Tumor Burden - drug effects</subject><subject>Tumor Burden - radiation effects</subject><subject>Young Adult</subject><issn>0923-7534</issn><issn>1569-8041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNqFkUFvFCEUx4nR2G316NVwrDFYmJllZjyYbDatmm70oCbeCMM8uigDE2A2GT9MP2vZjDZ6aAwHEvi9P7z3Q-gFo28YbcsL6Zx36mLo54quH6EVW_OWNLRij9GKtkVJ6nVZnaDTGH9QSnlbtE_RSUmLzNV8hW43FlQyznT4ACFOEatgfvnlxDicAsg0gEvESXMALJ0crYzJKGznYdz7QeKfxskIZPTRpCNzvtldv36F879IHKS1RIG12E7uBivpFIS3ePvpCwatjZJqxgHiZFPEOvgBpz3gze7yO45p6udn6ImWNsLz3_sZ-nZ1-XX7gew-v_-43eyIyt0lUtK6zKvgnHXrou9qVVWS95o1dVNAT3XLGgal4rVWVGmpeFN2DIAVui501ZZn6N2SO07dAL3KDQdpxRjMIMMsvDTi3xtn9uLGHwQvWto0xwCyBKjgYwyg72sZFUdRYhElFlGZf_n3g_f0HzMZOF8AP43_zaoXFPKEDgaCiMpAHnRvQpYrem8eqLwDOvi24g</recordid><startdate>20181101</startdate><enddate>20181101</enddate><creator>Gadgeel, S.</creator><creator>Peters, S.</creator><creator>Mok, T.</creator><creator>Shaw, A.T.</creator><creator>Kim, D.W.</creator><creator>Ou, S.I.</creator><creator>Pérol, M.</creator><creator>Wrona, A.</creator><creator>Novello, S.</creator><creator>Rosell, R.</creator><creator>Zeaiter, A.</creator><creator>Liu, T.</creator><creator>Nüesch, E.</creator><creator>Balas, B.</creator><creator>Camidge, D.R.</creator><general>Elsevier Ltd</general><general>Oxford University Press</general><scope>6I.</scope><scope>AAFTH</scope><scope>TOX</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0412-7143</orcidid></search><sort><creationdate>20181101</creationdate><title>Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study</title><author>Gadgeel, S. ; Peters, S. ; Mok, T. ; Shaw, A.T. ; Kim, D.W. ; Ou, S.I. ; Pérol, M. ; Wrona, A. ; Novello, S. ; Rosell, R. ; Zeaiter, A. ; Liu, T. ; Nüesch, E. ; Balas, B. ; Camidge, D.R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c534t-30737372661b52db7c44a6df18782ed0f9181e3c67fc0cfac683b1ee12f72f493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>alectinib</topic><topic>ALK-positive</topic><topic>Anaplastic Lymphoma Kinase - antagonists & inhibitors</topic><topic>Anaplastic Lymphoma Kinase - genetics</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - drug effects</topic><topic>Brain - radiation effects</topic><topic>Brain Neoplasms - diagnostic imaging</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - secondary</topic><topic>Brain Neoplasms - therapy</topic><topic>Carbazoles - pharmacology</topic><topic>Carbazoles - therapeutic use</topic><topic>Carcinoma, Non-Small-Cell Lung - diagnostic imaging</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - secondary</topic><topic>Carcinoma, Non-Small-Cell Lung - therapy</topic><topic>Chemoradiotherapy - methods</topic><topic>CNS</topic><topic>Crizotinib - pharmacology</topic><topic>Crizotinib - therapeutic use</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Humans</topic><topic>Lung - diagnostic imaging</topic><topic>Lung - drug effects</topic><topic>Lung - radiation effects</topic><topic>Lung Neoplasms - diagnostic imaging</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - pathology</topic><topic>Lung Neoplasms - therapy</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Middle Aged</topic><topic>NSCLC</topic><topic>Original articles</topic><topic>Piperidines - pharmacology</topic><topic>Piperidines - therapeutic use</topic><topic>Treatment Outcome</topic><topic>Tumor Burden - drug effects</topic><topic>Tumor Burden - radiation effects</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gadgeel, S.</creatorcontrib><creatorcontrib>Peters, S.</creatorcontrib><creatorcontrib>Mok, T.</creatorcontrib><creatorcontrib>Shaw, A.T.</creatorcontrib><creatorcontrib>Kim, D.W.</creatorcontrib><creatorcontrib>Ou, S.I.</creatorcontrib><creatorcontrib>Pérol, M.</creatorcontrib><creatorcontrib>Wrona, A.</creatorcontrib><creatorcontrib>Novello, S.</creatorcontrib><creatorcontrib>Rosell, R.</creatorcontrib><creatorcontrib>Zeaiter, A.</creatorcontrib><creatorcontrib>Liu, T.</creatorcontrib><creatorcontrib>Nüesch, E.</creatorcontrib><creatorcontrib>Balas, B.</creatorcontrib><creatorcontrib>Camidge, D.R.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Oxford Journals Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Annals of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gadgeel, S.</au><au>Peters, S.</au><au>Mok, T.</au><au>Shaw, A.T.</au><au>Kim, D.W.</au><au>Ou, S.I.</au><au>Pérol, M.</au><au>Wrona, A.</au><au>Novello, S.</au><au>Rosell, R.</au><au>Zeaiter, A.</au><au>Liu, T.</au><au>Nüesch, E.</au><au>Balas, B.</au><au>Camidge, D.R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study</atitle><jtitle>Annals of oncology</jtitle><addtitle>Ann Oncol</addtitle><date>2018-11-01</date><risdate>2018</risdate><volume>29</volume><issue>11</issue><spage>2214</spage><epage>2222</epage><pages>2214-2222</pages><issn>0923-7534</issn><eissn>1569-8041</eissn><abstract>The phase III ALEX study in patients with treatment-naive advanced anaplastic lymphoma kinase mutation-positive (ALK+) non-small-cell lung cancer (NSCLC) met its primary end point of improved progression-free survival (PFS) with alectinib versus crizotinib. Here, we present detailed central nervous system (CNS) efficacy data from ALEX.
Overall, 303 patients aged ≥18 years underwent 1:1 randomization to receive twice-daily doses of alectinib 600 mg or crizotinib 250 mg. Brain imaging was conducted in all patients at baseline and every subsequent 8 weeks. End points (analyzed by subgroup: patients with/without baseline CNS metastases; patients with/without prior radiotherapy) included PFS, CNS objective response rate (ORR), and time to CNS progression.
In total, 122 patients had Independent Review Committee-assessed baseline CNS metastases (alectinib,n = 64; crizotinib,n = 58), 43 had measurable lesions (alectinib,n = 21; crizotinib,n = 22), and 46 had received prior radiotherapy (alectinib,n = 25; crizotinib,n = 21). Investigator-assessed PFS with alectinib was consistent between patients with baseline CNS metastases [hazard ratio (HR) 0.40, 95% confidence interval (CI): 0.25–0.64] and those without (HR 0.51, 95% CI: 0.33–0.80,P interaction = 0.36). Similar results were seen in patients regardless of prior radiotherapy. Time to CNS progression was significantly longer with alectinib versus crizotinib and comparable between patients with and without baseline CNS metastases (P < 0.0001). CNS ORR was 85.7% with alectinib versus 71.4% with crizotinib in patients who received prior radiotherapy and 78.6% versus 40.0%, respectively, in those who had not.
Alectinib demonstrated superior CNS activity and significantly delayed CNS progression versus crizotinib in patients with previously untreated, advancedALK+ NSCLC, irrespective of prior CNS disease or radiotherapy.
ClinicalTrials.gov NCT02075840</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>30215676</pmid><doi>10.1093/annonc/mdy405</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-0412-7143</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over alectinib ALK-positive Anaplastic Lymphoma Kinase - antagonists & inhibitors Anaplastic Lymphoma Kinase - genetics Brain - diagnostic imaging Brain - drug effects Brain - radiation effects Brain Neoplasms - diagnostic imaging Brain Neoplasms - genetics Brain Neoplasms - secondary Brain Neoplasms - therapy Carbazoles - pharmacology Carbazoles - therapeutic use Carcinoma, Non-Small-Cell Lung - diagnostic imaging Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - secondary Carcinoma, Non-Small-Cell Lung - therapy Chemoradiotherapy - methods CNS Crizotinib - pharmacology Crizotinib - therapeutic use Disease Progression Female Humans Lung - diagnostic imaging Lung - drug effects Lung - radiation effects Lung Neoplasms - diagnostic imaging Lung Neoplasms - genetics Lung Neoplasms - pathology Lung Neoplasms - therapy Magnetic Resonance Imaging Male Middle Aged NSCLC Original articles Piperidines - pharmacology Piperidines - therapeutic use Treatment Outcome Tumor Burden - drug effects Tumor Burden - radiation effects Young Adult |
| title | Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study |
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