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A Survey of Japanese Thoracic Oncologists’ Perception of Diagnostic and Treatment Strategies for EGFR Mutant or EML4-ALK Fusion Non-small Cell Lung CancerOncologists’ Perceptions of Lung Cancer FREE TO VIEW

Katsuyuki Hotta, MD, PhD, MPH; Katsuyuki Kiura, MD, PhD; Masahiro Tabata, MD, PhD; Nagio Takigawa, MD, PhD; Mitsune Tanimoto, MD, PhD; Hiroshi Ueoka, MD, PhD
Author and Funding Information

From the Department of Hematology and Oncology (Drs Hotta and Tanimoto), the Department of Respiratory Medicine (Dr Kiura), and the Center for Oncology (Dr Tabata), Okayama University Hospital; the Department of General Internal Medicine 4 (Dr Takigawa), Kawasaki Hospital, Kawasaki Medical School; and the Department of Medical Oncology (Dr Ueoka), National Hospital Organization Yamaguchi-Ube Medical Center.

CORRESPONDENCE TO: Katsuyuki Hotta, MD, PhD, MPH, Department of Hematology and Oncology, Okayama University Hospital, 2-5-1, Shikata-cho, Kitaku, Okayama, 700-8558, Japan; e-mail: khotta@md.okayama-u.ac.jp


FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST the following conflicts of interest: Dr Hotta has received honoraria from Pfizer, Inc; Eli Lilly Japan; Sanofi SA; Daiichi-Sankyo, Inc; and Chugai Pharmaceutical Co Ltd. Drs Kiura and Takigawa have received honoraria from Pfizer, Inc; Eli Lilly Japan; Sanofi SA; Daiichi-Sankyo, Inc; Boehringer-Ingelheim GmbH; Chugai Pharmaceutical Co Ltd; and AstraZeneca. Drs Tabata, Tanimoto, and Ueoka have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(6):e222-e225. doi:10.1378/chest.14-2055
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Published online
To the Editor:

In non-small cell lung cancer (NSCLC), several driver oncogenes, including epidermal growth factor receptor (EGFR) and echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK), have been found. This has led to the development of personalized therapy with EGFR- or ALK-tyrosine kinase inhibitor (TKI); however, in clinical practice, oncologists’ perceptions of the diagnostic and treatment strategies have not been fully assessed.

In the fall of 2012, 871 Japanese thoracic oncologists volunteered to complete a self-administered anonymous questionnaire regarding diagnostic and treatment strategies for EGFR-mutant or ALK-rearranged NSCLC (Table 1). This survey was approved by the institutional review board.

Table Graphic Jump Location
TABLE 1 ]  A Self-Administered Anonymous Questionnaire Regarding Diagnostic and Treatment Strategies for EGFR-Mutant or ALK-Rearranged NSCLC

The following findings had been reported before the fall of 2012: (1) several phase 3 trials of EGFR-TKIs vs chemotherapy for EGFR-mutant NSCLC showed no difference in overall survival,2 but better quality of life for the former treatment3; (2) a direct overall survival comparison regarding crizotinib (ALK-TKI) vs chemotherapy had not yet been reported,4 although crizotinib yielded a dramatic response1; (3) erlotinib for first-line use, crizotinib, and afatinib had not yet been approved by the Japanese government; (4) National Comprehensive Cancer Network guidelines recommended first-line erlotinib or crizotinib monotherapy when an EGFR-mutation or ALK-rearrangement was detected at the initial diagnosis; (5) the Japanese guideline recommended the testing for an EGFR mutation and ALK rearrangement in nonsquamous cell NSCLC and the administration of first-line EGFR-TKI or platinum-based chemotherapy if the tumor possessed an EGFR mutation; and (6) systematic recommendations for the molecular analysis required to guide EGFR- and ALK-directed therapies had not yet been reported.5 ALK = anaplastic lymphoma kinase; EGFR = epidermal growth factor receptor; NSCLC = non-small cell lung cancer; PFS = progression-free survival; PS = performance status; TKI = tyrosine kinase inhibitor.

Of the respondents, 775 (89%) and 525 (60%) perceived EGFR mutations and ALK rearrangements to be tested at the time of diagnosis, respectively (Q4-1 and Q4-3, Table 1). The subjects also believed patients with EGFR wild-type tumors would selectively undergo testing for ALK status (n = 493, 57%), rather than all patients with NSCLC (n = 139, 16%) (Q4-2).

About one-half (n = 453, 52%) preferred gefitinib use over platinum in a first-line setting for EGFR-mutant NSCLC (Q5-1). They largely believed it yielded better progression-free survival (PFS) (n = 147, 32%) and better quality of life (n = 101, 22%) (Q5-2). By contrast, among subjects who chose platinum-based chemotherapy rather than EGFR-TKI use (n = 364, 42%), 137 (38%) thought it could be used just while a good performance status was retained, whereas few believed it could produce a better quality of life (n = 6, 2%) (Q5-1, Q5-2). All these clearly suggested that what was valued more appeared quite different among the subjects regarding the choice of first-line therapy with EGFR-TKI or platinum.

Among the participants, 379 (44%) would use crizotinib in a first-line setting for ALK-rearranged NSCLC; they mainly assumed that crizotinib yielded better PFS data based on the earlier trial result1 (n = 153, 40%). In contrast, 447 (51%) chose first-line platinum; they seemingly wanted to administer it when patients were still in good condition (n = 151, 34%) (Q6-1, Q6-2).

For patients whose tumors proved to possess EGFR mutations, most of the participants thought EGFR-TKI should be used before the initiation of third-line chemotherapy at the latest (n = 683, 78%) as similarly as they thought platinum-based chemotherapy should be administered (n = 724, 83%) (Q5-3, Q5-4). In addition, > 70% of the subjects stated that both crizotinib and platinum are important to be administered for ALK-positive NSCLC in a first- or second-line setting (Q6-3, Q6-4).

In conclusion, most participants perceived the importance of driver oncogene-based treatment by testing driver oncogenes and the use of TKIs and existing platinum-based therapy in the early line of treatment, despite disagreement regarding the treatment sequence. Clarifying how the subject’s perception would have further changed is warranted in a future study.

Acknowledgments

Other contributions: The authors thank all the participants who made this study possible.

Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363(18):1693-1703. [CrossRef] [PubMed]
 
Maemondo M, Inoue A, Kobayashi K, et al; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362(25):2380-2388. [CrossRef] [PubMed]
 
Oizumi S, Kobayashi K, Inoue A, et al. Quality of life with gefitinib in patients with EGFR-mutated non-small cell lung cancer: quality of life analysis of North East Japan Study Group 002 Trial. Oncologist. 2012;17(6):863-870. [CrossRef] [PubMed]
 
Mok TS. First-line crizotinib versus pemetrexed-cisplatin or pemetrexed-carboplatin in patients (pts) with advanced ALK-positive non-squamous non-small cell lung cancer (NSCLC): results of a phase III study (PROFILE 1014) [abstract]. J Clin Oncol. 2014;32(suppl):8002.
 
Lindeman NI, Cagle PT, Beasley MB, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Thorac Oncol. 2013;8(7):823-859. [CrossRef] [PubMed]
 

Figures

Tables

Table Graphic Jump Location
TABLE 1 ]  A Self-Administered Anonymous Questionnaire Regarding Diagnostic and Treatment Strategies for EGFR-Mutant or ALK-Rearranged NSCLC

The following findings had been reported before the fall of 2012: (1) several phase 3 trials of EGFR-TKIs vs chemotherapy for EGFR-mutant NSCLC showed no difference in overall survival,2 but better quality of life for the former treatment3; (2) a direct overall survival comparison regarding crizotinib (ALK-TKI) vs chemotherapy had not yet been reported,4 although crizotinib yielded a dramatic response1; (3) erlotinib for first-line use, crizotinib, and afatinib had not yet been approved by the Japanese government; (4) National Comprehensive Cancer Network guidelines recommended first-line erlotinib or crizotinib monotherapy when an EGFR-mutation or ALK-rearrangement was detected at the initial diagnosis; (5) the Japanese guideline recommended the testing for an EGFR mutation and ALK rearrangement in nonsquamous cell NSCLC and the administration of first-line EGFR-TKI or platinum-based chemotherapy if the tumor possessed an EGFR mutation; and (6) systematic recommendations for the molecular analysis required to guide EGFR- and ALK-directed therapies had not yet been reported.5 ALK = anaplastic lymphoma kinase; EGFR = epidermal growth factor receptor; NSCLC = non-small cell lung cancer; PFS = progression-free survival; PS = performance status; TKI = tyrosine kinase inhibitor.

References

Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363(18):1693-1703. [CrossRef] [PubMed]
 
Maemondo M, Inoue A, Kobayashi K, et al; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362(25):2380-2388. [CrossRef] [PubMed]
 
Oizumi S, Kobayashi K, Inoue A, et al. Quality of life with gefitinib in patients with EGFR-mutated non-small cell lung cancer: quality of life analysis of North East Japan Study Group 002 Trial. Oncologist. 2012;17(6):863-870. [CrossRef] [PubMed]
 
Mok TS. First-line crizotinib versus pemetrexed-cisplatin or pemetrexed-carboplatin in patients (pts) with advanced ALK-positive non-squamous non-small cell lung cancer (NSCLC): results of a phase III study (PROFILE 1014) [abstract]. J Clin Oncol. 2014;32(suppl):8002.
 
Lindeman NI, Cagle PT, Beasley MB, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Thorac Oncol. 2013;8(7):823-859. [CrossRef] [PubMed]
 
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