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Treatment Sequencing in Patients with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer in Japan: A Real-World Observational Study

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Abstract

Introduction

The anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) alectinib was approved in Japan in 2014 for the treatment of ALK fusion gene-positive advanced non-small cell lung cancer (NSCLC). With the approvals of crizotinib in 2012 and ceritinib in 2017, Japan became the first country with multiple ALK TKIs available for first-line or later use in patients with ALK-positive advanced NSCLC. Here, we collected and evaluated real-world data on ALK TKI clinical usage patterns and sequencing in patients with ALK-positive NSCLC in Japan.

Methods

This retrospective observational study used the Japanese Medical Data Vision database to analyze data from patients with a confirmed diagnosis of lung cancer who visited a healthcare facility in the database between April 2010 and March 2017, underwent an ALK test, received a prescription for an ALK TKI, and were at least 18 years old as of the date of the first ALK TKI prescription. There were no exclusion criteria. Descriptive analyses of demographics, baseline characteristics, ALK TKI treatment patterns and sequences, non-ALK TKI treatments received before, during, and after ALK TKI treatment, and treatment durations were reported.

Results

A total of 378 patients met the inclusion criteria and were evaluated in mutually exclusive groups of patients receiving one, two, or three ALK TKIs. The initial ALK TKI prescribed was crizotinib for 52.1% of patients and alectinib for 47.9% of patients; however, the proportion of patients receiving alectinib as the initial ALK TKI increased over time following the Japanese approval of alectinib in 2014. Of the 117 patients who received two or three ALK TKIs, 106 received crizotinib as the first ALK TKI and 11 received alectinib. Before the date of the patient’s first ALK TKI prescription, 153 of 378 patients (40.5%) had received chemotherapy. Of 104 patients who discontinued ALK therapy, 46.2% received chemotherapy and 5.8% received immunotherapy as their next treatment.

Conclusion

At the time of this analysis, most patients who received more than one ALK TKI received crizotinib as the initial ALK TKI. Additional ALK TKIs have since been approved in Japan as first-line or later therapeutic options for patients with ALK-positive NSCLC, but the optimal sequence of ALK TKI usage remains undetermined. As new data continue to emerge, additional research will be warranted to evaluate ALK TKI sequences that do not include crizotinib as the first therapy in this patient population.

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Acknowledgements

Funding

Research, data collection, data analysis, medical writing support and the journal’s Rapid Service Fee were funded by Pfizer Inc, the study sponsor.

Medical Writing and Editorial Assistance

Editorial and medical writing support was provided by Michelle Daniels of inScience Communications, Springer Healthcare (Philadelphia, PA, USA), and was funded by Pfizer Inc.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Authorship Contributions

Y. Goto contributed to conceptualization, formal analysis, writing, reviewing and editing the manuscript. N. Yamamoto contributed to conceptualization, formal analysis, writing, reviewing and editing the manuscript. E.T. Masters contributed to conceptualization, data curation, formal analysis, methodology, writing, reviewing and editing the manuscript. H. Kikkawa contributed to conceptualization, data curation, methodology, writing, reviewing and editing the manuscript. J. Mardekian contributed to conceptualization, formal analysis, methodology, validation, reviewing and editing the manuscript. R. Wiltshire contributed to conceptualization, formal analysis, methodology, writing, reviewing and editing the manuscript. K. Togo contributed to formal analysis, methodology, writing, reviewing and editing the manuscript. Y. Ohe contributed to conceptualization, formal analysis, writing, reviewing and editing the manuscript.

Disclosures

Y. Goto has served in a consulting or advisory role for AstraZeneca, Boehringer Ingelheim, Chugai, Eli Lilly, Glaxo Smith Kline, Novartis, Pfizer, Taiho Pharmaceutical, on the speaker’s bureau for AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Chugai, MSD Novartis, Ono Pharmaceutical, Pfizer, Shionogi Pharma, Taiho Pharmaceutical and received research funding from AbbVie, Bristol Myers Squibb, Eli Lilly, Ono Pharmaceutical, Taiho Pharmaceutical. N. Yamamoto has received honoraria from AstraZeneca, Bristol-Myers Squibb Japan, Chugai Pharma, Lilly Japan, Ono Pharmaceutical, Pfizer, served in a consultant or advisory role for Esai, OncoTherapy Science, and Takeda and is affiliated with an institution that has received research funding from Astellas, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Esai, Kyowa-Hakko Kirin, Novartis, Ono Pharmaceutical, Pfizer, Quintiles, Taiho, and Takeda. E.T. Masters is an employee of and owns stock in Pfizer Inc. H. Kikkawa is an employee of Pfizer Japan Inc. and owns stock in Pfizer Inc. J. Mardekian is a former employee of and owns stock in Pfizer Inc. R. Wiltshire is an employee of and owns stock in Pfizer Inc. K. Togo is an employee of Pfizer Japan Inc. and owns stock in Pfizer Inc. Y. Ohe has served on speakers and advisory boards for AstraZeneca, Chugai, Ono Pharmaceutical, received honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Kissei, Lilly, MSD, Ono Pharmaceutical, Pfizer, Taiho, and grant/research support from AstraZeneca, Bristol-Myers Squibb, Chugai, Dainippon-Sumitomo, Ignyta, Kyorin, Lilly, Novartis, Ono Pharmaceuticals, Pfizer, Taiho.

Compliance with Ethics Guidelines

Institutional review board approval and patient informed consent were not required for this observational study as it used secondary data devoid of any patient-identifying information. Pfizer Japan Inc. obtained agreement from the owner of the database, MDV Inc, to use the data within the database for this analysis.

Data Availability

The datasets generated during and/or analyzed during the current study are not publicly available as this is a commercial database and Pfizer Japan Inc. is under contract with the owner, MDV Inc., but are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Thoracic Oncology, National Cancer Center Hospital, 5 Chome-1-1 Tsukiji, Chūō City, Tokyo, 104-0045, Japan

    Yasushi Goto & Yuichiro Ohe

  2. Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama Prefecture, 641-8509, Japan

    Nobuyuki Yamamoto

  3. Health Economics and Outcomes Research, Pfizer Inc, 235 E 42 St, New York, NY, USA

    Elizabeth T. Masters

  4. Medical Affairs, Oncology, Pfizer Japan Inc, Shinjuku Bunka Quint Bldg.3-22-7, Yoyogi, Shibuya-ku, Tokyo, 151-0053, Japan

    Hironori Kikkawa

  5. Statistics, Pfizer Inc., 235 E 42 St, New York, NY, USA

    Jack Mardekian

  6. Oncology Global Medical Affairs, Pfizer Ltd, Walton Oaks, Tadworth, Surrey, KT20 7NS, UK

    Robin Wiltshire

  7. Corporate Affairs, Health and Value, Pfizer Japan Inc., Shinjuku Bunka Quint Bldg.3-22-7, Yoyogi, Shibuya-ku, Tokyo, 151-0053, Japan

    Kanae Togo

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  1. Yasushi Goto
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Correspondence to Yasushi Goto.

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Goto, Y., Yamamoto, N., Masters, E.T. et al. Treatment Sequencing in Patients with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer in Japan: A Real-World Observational Study. Adv Ther 37, 3311–3323 (2020). https://doi.org/10.1007/s12325-020-01392-0

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