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© 2020. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Lorlatinib is a potent, brain‐penetrant, third‐generation anaplastic lymphoma kinase (ALK)/ROS proto‐oncogene 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‐rearranged/ROS1‐rearranged advanced non–small 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‐ORR based on independent central review. Secondary endpoints included pharmacokinetic evaluations. At data cutoff, 39 ALK‐rearranged/ROS1‐rearranged Japanese patients were enrolled across the six expansion cohorts; all received lorlatinib 100 mg once daily. Thirty‐one ALK‐rearranged patients previously treated with ≥1 ALK TKI (EXP2 to EXP5) were evaluable for ORR and 15 were evaluable for IC‐ORR. The ORR and the IC‐ORR for Japanese patients in EXP2‐5 were 54.8% (95% confidence interval [CI]: 36.0‐72.7) and 46.7% (95% CI: 21.3‐73.4), respectively. Among patients who had received prior alectinib only (EXP3B), the ORR was 42.9%; 95% CI: 9.9‐81.6). The most common treatment‐related adverse event (TRAE) was hypercholesterolemia (79.5%). Hypertriglyceridemia was the most common grade 3/4 TRAE (25.6%). Single‐dose and multiple‐dose pharmacokinetic profiles among Japanese patients were similar to those in non–Japanese patients. Lorlatinib showed clinically meaningful responses and IC responses among ALK‐rearranged Japanese patients with NSCLC who received ≥1 prior ALK TKI, including meaningful responses among those receiving prior alectinib only. Lorlatinib was generally well tolerated.

Details

Title
Lorlatinib in previously treated anaplastic lymphoma kinase‐rearranged non–small cell lung cancer: Japanese subgroup analysis of a global study
Author
Seto, Takashi 1 ; Hayashi, Hidetoshi 2 ; Satouchi, Miyako 3 ; Goto, Yasushi 4 ; Niho, Seiji 5 ; Nogami, Naoyuki 6 ; Hida, Toyoaki 7   VIAFID ORCID Logo  ; Takahashi, Toshiaki 8 ; Sakakibara‐Konishi, Jun 9 ; Morise, Masahiro 10 ; Nagasawa, Takashi 11 ; Suzuki, Mie 12 ; Ohkura, Masayuki 12 ; Fukuhara, Kei 12 ; Thurm, Holger 13 ; Peltz, Gerson 13 ; Nishio, Makoto 14   VIAFID ORCID Logo 

 National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan 
 Faculty of Medicine, Kindai University, Osaka, Japan 
 Hyogo Cancer Center, Akashi, Japan 
 National Cancer Center Hospital, Tokyo, Japan 
 National Cancer Center Hospital East, Kashiwa, Japan 
 National Hospital Organization Shikoku Cancer Center, Ehime, Japan 
 Aichi Cancer Center Hospital, Nagoya, Japan 
 Shizuoka Cancer Center, Nagaizumi, Japan 
 Hokkaido University Hospital, Sapporo, Japan 
10  Nagoya University Graduate School of Medicine, Nagoya, Japan 
11  Pfizer Japan, Tokyo, Japan 
12  Pfizer R&D Japan, Tokyo, Japan 
13  Pfizer Oncology, La Jolla, CA, USA 
14  The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan 
Pages
3726-3738
Section
CLINICAL RESEARCH
Publication year
2020
Publication date
Oct 1, 2020
Publisher
John Wiley & Sons, Inc.
ISSN
13479032
e-ISSN
13497006
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3165294882
Copyright
© 2020. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.