{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T23:06:19Z","timestamp":1782860779961,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,9,11]],"date-time":"2020-09-11T00:00:00Z","timestamp":1599782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lorlatinib is a potent, brain\u2010penetrant, third\u2010generation anaplastic lymphoma kinase (ALK)\/ROS proto\u2010oncogene 1 (ROS1) tyrosine kinase inhibitor (TKI) that is active against most known resistance mutations. This is an ongoing phase 1\/2, multinational study (NCT01970865) investigating the efficacy, safety and pharmacokinetics of lorlatinib in ALK\u2010rearranged\/ROS1\u2010rearranged advanced non\u2013small cell lung cancer (NSCLC) with or without intracranial (IC) metastases. Because patterns of ALK TKI use in Japan differ from other regions, we present a subgroup analysis of Japanese patients. Patients were enrolled into six expansion (EXP) cohorts based on ALK\/ROS1 mutation status and treatment history. The primary endpoint was the objective response rate (ORR) and the IC\u2010ORR based on independent central review. Secondary endpoints included pharmacokinetic evaluations. At data cutoff, 39 ALK\u2010rearranged\/ROS1\u2010rearranged Japanese patients were enrolled across the six expansion cohorts; all received lorlatinib 100\u00a0mg once daily. Thirty\u2010one ALK\u2010rearranged patients previously treated with\u00a0\u22651 ALK TKI (EXP2 to EXP5) were evaluable for ORR and 15 were evaluable for IC\u2010ORR. The ORR and the IC\u2010ORR for Japanese patients in EXP2\u20105 were 54.8% (95% confidence interval [CI]: 36.0\u201072.7) and 46.7% (95% CI: 21.3\u201073.4), respectively. Among patients who had received prior alectinib only (EXP3B), the ORR was 42.9%; 95% CI: 9.9\u201081.6). The most common treatment\u2010related adverse event (TRAE) was hypercholesterolemia (79.5%). Hypertriglyceridemia was the most common grade 3\/4 TRAE (25.6%). Single\u2010dose and multiple\u2010dose pharmacokinetic profiles among Japanese patients were similar to those in non\u2013Japanese patients. Lorlatinib showed clinically meaningful responses and IC responses among ALK\u2010rearranged Japanese patients with NSCLC who received \u22651 prior ALK TKI, including meaningful responses among those receiving prior alectinib only. Lorlatinib was generally well tolerated.<\/jats:p>","DOI":"10.1111\/cas.14576","type":"journal-article","created":{"date-parts":[[2020,7,18]],"date-time":"2020-07-18T11:13:46Z","timestamp":1595070826000},"page":"3726-3738","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Lorlatinib in previously treated anaplastic lymphoma kinase\u2010rearranged non\u2013small cell lung cancer: Japanese subgroup analysis of a global study"],"prefix":"10.1111","volume":"111","author":[{"given":"Takashi","family":"Seto","sequence":"first","affiliation":[{"name":"National Hospital Organization Kyushu Cancer Center Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Kindai University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyako","family":"Satouchi","sequence":"additional","affiliation":[{"name":"Hyogo Cancer Center Akashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Goto","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiji","family":"Niho","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital East Kashiwa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyuki","family":"Nogami","sequence":"additional","affiliation":[{"name":"National Hospital Organization Shikoku Cancer Center Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3537-0020","authenticated-orcid":false,"given":"Toyoaki","family":"Hida","sequence":"additional","affiliation":[{"name":"Aichi Cancer Center Hospital Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Shizuoka Cancer Center Nagaizumi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Sakakibara\u2010Konishi","sequence":"additional","affiliation":[{"name":"Hokkaido University Hospital Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Morise","sequence":"additional","affiliation":[{"name":"Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Nagasawa","sequence":"additional","affiliation":[{"name":"Pfizer Japan Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mie","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Pfizer R&amp;D Japan Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Ohkura","sequence":"additional","affiliation":[{"name":"Pfizer R&amp;D Japan Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Fukuhara","sequence":"additional","affiliation":[{"name":"Pfizer R&amp;D Japan Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Thurm","sequence":"additional","affiliation":[{"name":"Pfizer Oncology La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerson","family":"Peltz","sequence":"additional","affiliation":[{"name":"Pfizer Oncology La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4969-4165","authenticated-orcid":false,"given":"Makoto","family":"Nishio","sequence":"additional","affiliation":[{"name":"The Cancer Institute Hospital of Japanese Foundation for Cancer Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.025"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0168"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e3181c4dedb"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-6186"},{"key":"e_1_2_8_6_1","unstructured":"US Food and Drug Administration.Crizotinib US prescribing information.http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2014\/202570s011lbl.pdf. Accessed October 15 2019"},{"key":"e_1_2_8_7_1","unstructured":"European Medicines Agency.Crizotinib EU prescribing information.http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/EPAR_\u2010_Product_Information\/human\/002489\/WC500134759.pdf. Accessed October 15 2019"},{"key":"e_1_2_8_8_1","unstructured":"Pharmaceuticals and Medical Devices Agency.Report on the deliberation results (crizotinib). March 2012.https:\/\/www.pmda.go.jp\/files\/000153949.pdf. Accessed October 15 2019"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.34.1313"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1214886"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0201425"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-13-0846"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2014.05.020"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.65.5936"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70362-6"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00614-2"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy121"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy121"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.63.9443"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1704795"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00488-X"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1311107"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30339-X"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30123-X"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2017.06.070"},{"key":"e_1_2_8_26_1","unstructured":"Pharmaceuticals and Medical Devices Agency.Report on the deliberation results (alectinib). June 2014.https:\/\/www.pmda.go.jp\/files\/000208811.pdf. Accessed October 15 2019"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70142-6"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30565-2"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-019-01431-z"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-0596"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm500261q"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30680-0"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30649-1"},{"key":"e_1_2_8_34_1","unstructured":"Pharmaceuticals and Medical Devices Agency.Report on the deliberation results (lorlatinib). September 2018. http:\/\/www.pmda.go.jp\/files\/000228981.pdf. Accessed October 15 2019."},{"key":"e_1_2_8_35_1","unstructured":"US Food and Drug Administration.Lorlatinib US prescribing information.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/210868s000lbl.pdf. Accessed October 15 2019"},{"key":"e_1_2_8_36_1","unstructured":"European Medicines Agency.Lorlatinib EU prescribing information.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/lorviqua\u2010epar\u2010product\u2010information_en.pdf. Accessed October 15 2019"},{"key":"e_1_2_8_37_1","unstructured":"US Food and Drug Administration.Alectinib US prescribing information.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/208434s004lbl.pdf. Accessed January 1 2020"},{"key":"e_1_2_8_38_1","unstructured":"European Medicines Agency.Alectinib EU prescribing information.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/alecensa\u2010epar\u2010product\u2010information_en.pdf. Accessed October 15 2019."},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1810171"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1408440"},{"key":"e_1_2_8_41_1","unstructured":"KuznarW.Updated NCCN guidelines expand targeted therapy options for patients with metastatic NSCLC.http:\/\/oncpracticemanagement.com\/issues\/2018\/july\u20102018\u2010vol\u20108\u2010no\u20107\/613\u2010updated\u2010nccn\u2010guidelines\u2010expand\u2010targeted\u2010therapy\u2010options\u2010for\u2010patients\u2010with\u2010metastatic\u2010nsclc. Accessed February 5 2019"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcas.14576","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.14576","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.14576","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.14576","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T10:23:39Z","timestamp":1739269419000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.14576"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,11]]},"references-count":40,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1111\/cas.14576"],"URL":"https:\/\/doi.org\/10.1111\/cas.14576","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,11]]},"assertion":[{"value":"2020-05-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}