Disproportionality Analysis of Osimertinib-related Adverse Events in Elderly Patients Using the Japanese Pharmacovigilance Database

Overview

Journal Cancer Diagn Progn

Specialty Oncology

Date 2024 Sep 6

PMID 39238633

Authors

Takashi Omoto

Junichi Asaka

Kenzo Kudo

Affiliations

Soon will be listed here.

Abstract

Background/aim: Osimertinib is a well-tolerated first- or second-line treatment option for elderly patients with epidermal growth factor receptor mutation-positive advanced non-small cell lung cancer. However, the safety of osimertinib in elderly patients requires further investigation. Herein, we identified safety signals for various osimertinib-related adverse events (AEs) in elderly patients by disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database.

Patients And Methods: Data from the JADER database from April 2004 to March 2023 were obtained from the Pharmaceuticals and Medical Devices Agency website. Safety signal detection for osimertinib-related AEs in elderly patients (≥70 years old) was determined using the relative elderly reporting odds ratio (ROR). For osimertinib-related AEs, we extracted 92 preferred terms (PTs) and nine standardized MedDRA queries (SMQs).

Results: Safety signals in elderly patients were detected for "Cardiomyopathy (PT)" and "Cardiomyopathy (SMQ)". The symptoms most frequently associated with "Cardiomyopathy (SMQ)" included "Ejection fraction decreased (PT)", "Cardiomyopathy (PT)", and "Stress cardiomyopathy (PT)". Notably, 53.7% of these outcomes were "Recovery" or "Remission". The median time to the onset of "Cardiomyopathy (SMQ)" in elderly patients was 85 days (range=2-537 days).

Conclusion: We demonstrated that patients ≥70 years potentially have increased osimertinib-related cardiomyopathy compared with patients <70 years. In the future, it is necessary to conduct research focusing on cardiomyopathy in elderly patients.

References

Yoon H, Kim K, Kim H, Park H, Cho J, Hong Y . Impacts of non-recovery of trastuzumab-induced cardiomyopathy on clinical outcomes in patients with breast cancer. Clin Res Cardiol. 2019; 108(8):892-900. DOI: 10.1007/s00392-019-01417-x. View

Ewer M, Lippman S . Type II chemotherapy-related cardiac dysfunction: time to recognize a new entity. J Clin Oncol. 2005; 23(13):2900-2. DOI: 10.1200/JCO.2005.05.827. View

Serrano C, Cortes J, De Mattos-Arruda L, Bellet M, Gomez P, Saura C . Trastuzumab-related cardiotoxicity in the elderly: a role for cardiovascular risk factors. Ann Oncol. 2011; 23(4):897-902. DOI: 10.1093/annonc/mdr348. View

Soria J, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee K . Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2017; 378(2):113-125. DOI: 10.1056/NEJMoa1713137. View

Sacher A, Le L, Leighl N, Coate L . Elderly patients with advanced NSCLC in phase III clinical trials: are the elderly excluded from practice-changing trials in advanced NSCLC?. J Thorac Oncol. 2013; 8(3):366-8. DOI: 10.1097/JTO.0b013e31827e2145. View

Midha A, Dearden S, McCormack R . EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res. 2015; 5(9):2892-911. PMC: 4633915. View

Hanna N, Johnson D, Temin S, Baker Jr S, Brahmer J, Ellis P . Systemic Therapy for Stage IV Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2017; 35(30):3484-3515. DOI: 10.1200/JCO.2017.74.6065. View

Chihara Y, Takeda T, Goto Y, Nakamura Y, Tsuchiya-Kawano Y, Nakao A . A Phase II Trial on Osimertinib as a First-Line Treatment for EGFR Mutation-Positive Advanced NSCLC in Elderly Patients: The SPIRAL-0 Study. Oncologist. 2022; 27(11):903-e834. PMC: 9632307. DOI: 10.1093/oncolo/oyac193. View

Ito K, Koseki T, Morisaku M, Yamada S, Hayakawa N . Cytomegalovirus Occurrence and Time-to-onset Analysis Under Bendamustine With Anti-CD20 Antibodies Using the JADER Database. In Vivo. 2024; 38(2):923-927. PMC: 10905466. DOI: 10.21873/invivo.13520. View

10.

Shinomiya S, Kaira K, Yamaguchi O, Ishikawa K, Kagamu H . Osimertinib induced cardiomyopathy: A case report. Medicine (Baltimore). 2020; 99(39):e22301. PMC: 7523866. DOI: 10.1097/MD.0000000000022301. View

11.

Chen J, Long J, Hurria A, Owusu C, Steingart R, Gross C . Incidence of heart failure or cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J Am Coll Cardiol. 2012; 60(24):2504-12. DOI: 10.1016/j.jacc.2012.07.068. View

12.

Erickson S, OShea K, Ghaboosi N, Loverro L, Frantz G, Bauer M . ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2-and heregulin-deficient mice. Development. 1997; 124(24):4999-5011. DOI: 10.1242/dev.124.24.4999. View

13.

Omoto T, Asaka J, Sakai T, Sato F, Goto N, Kudo K . Disproportionality Analysis of Safety Signals for a Wide Variety of Opioid-Related Adverse Events in Elderly Patients Using the Japanese Adverse Drug Event Report (JADER) Database. Biol Pharm Bull. 2021; 44(5):627-634. DOI: 10.1248/bpb.b20-00904. View

14.

Cross D, Ashton S, Ghiorghiu S, Eberlein C, Nebhan C, Spitzler P . AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014; 4(9):1046-61. PMC: 4315625. DOI: 10.1158/2159-8290.CD-14-0337. View

15.

Nakao A, Hiranuma O, Uchino J, Sakaguchi C, Kita T, Hiraoka N . Osimertinib in Elderly Patients with Epidermal Growth Factor Receptor T790M-Positive Non-Small-Cell Lung Cancer Who Progressed During Prior Treatment: A Phase II Trial. Oncologist. 2019; 24(5):593-e170. PMC: 6516134. DOI: 10.1634/theoncologist.2019-0003. View

16.

Ramalingam S, Vansteenkiste J, Planchard D, Cho B, Gray J, Ohe Y . Overall Survival with Osimertinib in Untreated, -Mutated Advanced NSCLC. N Engl J Med. 2019; 382(1):41-50. DOI: 10.1056/NEJMoa1913662. View

17.

Okuzumi S, Matsuda M, Nagao G, Kakimoto T, Minematsu N . Heart Failure With Reduced Ejection Fraction Caused by Osimertinib in a Patient With Lung Cancer: A Case Report and Literature Review. Cureus. 2022; 14(8):e27694. PMC: 9441008. DOI: 10.7759/cureus.27694. View

18.

Furuta H, Uemura T, Yoshida T, Kobara M, Yamaguchi T, Watanabe N . Efficacy and Safety Data of Osimertinib in Elderly Patients with NSCLC Who Harbor the T790M Mutation After Failure of Initial EGFR-TKI Treatment. Anticancer Res. 2018; 38(9):5231-5237. DOI: 10.21873/anticanres.12847. View

19.

Ishibashi M, Nakagawa Y, Shimizu T, Gon Y, Yamamoto H . Retrospective Analysis of the Incidence of Drug-Induced Interstitial Lung Disease by Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Survival in Patients Aged 75 Years or Older with Lung Cancer. JMA J. 2023; 6(2):182-187. PMC: 10169255. DOI: 10.31662/jmaj.2022-0211. View

20.

Patel S, Brown S, Kubusek J, Mansfield A, Duma N . Osimertinib-Induced Cardiomyopathy. JACC Case Rep. 2021; 2(4):641-645. PMC: 8298525. DOI: 10.1016/j.jaccas.2019.12.038. View