A phase II study of first-line afatinib for patients aged ≥75 years with EGFR mutation-positive advanced non-small cell lung cancer: North East Japan Study Group trial NEJ027

doi:10.1186/s12885-021-07861-1

Multicenter Study

. 2021 Mar 1;21(1):208.

doi: 10.1186/s12885-021-07861-1.

A phase II study of first-line afatinib for patients aged ≥75 years with EGFR mutation-positive advanced non-small cell lung cancer: North East Japan Study Group trial NEJ027

Affiliations

¹ Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 113-8603 1-1-5 Sendagi Bunkyo-Ku, Tokyo, Japan. yminegis@nms.ac.jp.
² Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397 Yamane, Hidaka City, Saitama, 350-1298, Japan.
³ Department of Pulmonary Medicine, Sendai Kousei Hospital, 4-15 Hirose-machi, Aoba-ku, Sendai, 980-0873, Japan.
⁴ Department of Respiratory Medicine, National Hospital Organization, Iwakuni Clinical Center, 1-1-1 Atago Cyo, Iwakuni City, Yamaguchi Prefecture, 740-8510, Japan.
⁵ Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachidori, Chuouku, Niigata, 951-8510, Japan.
⁶ Division of Respirology, NTT Medical Center Tokyo, 5-9-22 Higashigotanda Shinagawa, Tokyo, Japan.
⁷ Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center, 5-1-1 Toneyama, Toyonaka City, Osaka, 560-8552, Japan.
⁸ Respiratory Center, Matsusaka Municipal Hospital, 1550 Tonomachi, Matsusaka City, Mie, 515-8544, Japan.
⁹ Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
¹⁰ Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
¹¹ Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 113-8603 1-1-5 Sendagi Bunkyo-Ku, Tokyo, Japan.

PMID: 33648453
PMCID: PMC7919080
DOI: 10.1186/s12885-021-07861-1

Multicenter Study

A phase II study of first-line afatinib for patients aged ≥75 years with EGFR mutation-positive advanced non-small cell lung cancer: North East Japan Study Group trial NEJ027

Yuji Minegishi et al. BMC Cancer. 2021.

. 2021 Mar 1;21(1):208.

doi: 10.1186/s12885-021-07861-1.

Authors

Affiliations

¹ Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 113-8603 1-1-5 Sendagi Bunkyo-Ku, Tokyo, Japan. yminegis@nms.ac.jp.
² Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397 Yamane, Hidaka City, Saitama, 350-1298, Japan.
³ Department of Pulmonary Medicine, Sendai Kousei Hospital, 4-15 Hirose-machi, Aoba-ku, Sendai, 980-0873, Japan.
⁴ Department of Respiratory Medicine, National Hospital Organization, Iwakuni Clinical Center, 1-1-1 Atago Cyo, Iwakuni City, Yamaguchi Prefecture, 740-8510, Japan.
⁵ Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachidori, Chuouku, Niigata, 951-8510, Japan.
⁶ Division of Respirology, NTT Medical Center Tokyo, 5-9-22 Higashigotanda Shinagawa, Tokyo, Japan.
⁷ Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center, 5-1-1 Toneyama, Toyonaka City, Osaka, 560-8552, Japan.
⁸ Respiratory Center, Matsusaka Municipal Hospital, 1550 Tonomachi, Matsusaka City, Mie, 515-8544, Japan.
⁹ Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
¹⁰ Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
¹¹ Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 113-8603 1-1-5 Sendagi Bunkyo-Ku, Tokyo, Japan.

PMID: 33648453
PMCID: PMC7919080
DOI: 10.1186/s12885-021-07861-1

Abstract

Background: Lung cancer is most common among older individuals. However, polypharmacy and comorbidities, which are also more common in older individuals, can limit treatment options. Previous studies suggest that afatinib can be used safely and effectively in elderly patients. This study investigated the anti-tumour activity and safety profile of first-line afatinib in previously-untreated elderly Japanese patients with EGFR mutation-positive non-small cell lung cancer (NSCLC).

Methods: This was a single-arm, open-label, phase II study, performed in multiple centres in Japan. Previously untreated patients, aged ≥75 years, with EGFR mutation-positive (Del19 or L858R) advanced NSCLC were treated with afatinib 40 mg until disease progression or unacceptable toxicity. Adverse events (AEs) were managed with protocol-defined dose adjustments. The primary endpoint was objective response rate (ORR) by central review.

Results: In total, 38 patients received at least one dose of afatinib, and 37 were evaluable for response. Median age was 77.5 years (range 75-91), all patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and 60.5% had Del19-positive disease. Median follow-up was 838 days. ORR was 75.7% (2 complete responses and 26 partial responses). Median progression-free survival was 14.2 months (95% confidence interval [CI], 9.5-19.0). Median overall survival (OS) was 35.2 months (95% CI, 35.2-not reached); the 2-year OS rate was 78.3%. The most common grade 3/4 treatment-related AEs (TRAEs) were diarrhoea (28.9%), paronychia (23.7%), and rash/acne (15.8%). Dose reductions due to TRAEs were reported in 78.9% of patients, and eight (21.1%) patients discontinued afatinib due to TRAEs. No treatment-related deaths were reported.

Conclusion: Although dose adjustments were relatively common in this small group of Japanese patients aged ≥75 years with EGFR mutation-positive NSCLC, discontinuation occurred much less frequently, and most patients were able to stay on treatment for well over a year. Further, afatinib was associated with high response rates and prolonged PFS and OS.

Trial registration: The trial is registered with Japan Registry of Clinical Trials (JRCT) as trial number 031180136 (date of initial registration: 19 February 2019), and the University Hospital Network (UMIN) as trial number 000017877 (date of initial registration: 11 June 2015).

Keywords: Afatinib; Dose adjustment; EGFR mutation; Efficacy; Elderly patients; Japan; Non-small cell lung cancer; Safety.

PubMed Disclaimer

Conflict of interest statement

O.Y. reports honoraria from Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb, Taiho Pharmaceutical Co., Ltd., MSD, Chugai Pharmaceutical Co., Ltd., and AstraZeneca. S.S. reports honoraria from Nippon Boehringer Ingelheim Co., Ltd., AstraZeneca, Chugai Pharmaceutical Co., Ltd., MSD, Bristol-Myers Squibb, Ono Pharmaceutical Co., Ltd., Eli Lilly and Company, Pfizer, Novartis, Taiho Pharmaceutical Co., Ltd., and Kyowa Hakko Kirin Co., Ltd. S.W. reports honoraria from Eli Lilly and Company, Pfizer, Novartis, AstraZeneca, Chugai Pharmaceutical Co., Ltd., Bristol-Myers Squibb, Boehringer Ingelheim, MSD, Ono Pharmaceutical Co., Ltd., Daiichi Sankyo and Taiho Pharmaceutical Co., Ltd. M.M. reports honoraria from AstraZeneca, Boehringer Ingelheim, Chugai Pharmaceutical Co., Ltd., Eli Lilly and Company, MSD, Novartis Pharma, Ono Pharmaceutical Co., Ltd. and Taiho Pharmaceutical Co., Ltd. O.H. reports honoraria from AstraZeneca, Boehringer Ingelheim and Novartis, and grants or funds from GlaxoSmithKline, AstraZeneca, Novartis, Bayer Health Care, Boehringer Ingelheim and Daiichi Sankyo. S.M. reports honoraria from AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan, MSD, Nippon Boehringer Ingelheim Co., Ltd., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., and Taiho Pharmaceutical Co., Ltd., and research funding to their institution from Nippon Boehringer Ingelheim Co., Ltd. K.K. reports honoraria (speech fees) from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Eli Lilly and Company, Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co. and Ono Pharmaceutical Co., Ltd. A.G. reports honoraria from Boehringer Ingelheim. Y.M., S.K., K.U., and T.N. declare no conflict of interest.

Figures

**Fig. 1**
Kaplan–Meier survival analysis in the full analysis set (*n =* 37). a Progression-free survival (PFS)^a. b Overall survival (OS). c Time to treatment failure (TTF). Abbreviations: CI confidence interval, NR not reached, *QOD* every other day. ^aPFS was censored for four patients receiving afatinib < 20 mg/day. These patients were treated as censored when they fell below the 20 mg/day minimum dose specified in the protocol

**Fig. 2**
Treatment duration and afatinib dose in the safety analysis set (*n =* 38). Abbreviations: AE adverse event, CR complete response, NE not evaluable; OT other, PD progressive disease, PR partial response; *QOD* every other day, SD stable disease. ^aFor Patient 21, protocol treatment was discontinued due to disease progression; Thereafter, afatinib treatment beyond PD was discontinued due to skin disorders. ^bPatient 23 had no appropriate measurable lesion and was not included in the full analysis set

See this image and copyright information in PMC

Cited by

Efficacy of erlotinib and its effects on the quality of life of older patients with epidermal growth factor receptor-mutant non-small cell lung cancer: A prospective, multicenter, dose-modification study.
Tsubata Y, Masuda T, Hamai K, Taniwaki M, Tanino A, Hotta T, Hamaguchi M, Hamaguchi S, Yamasaki M, Ishikawa N, Fujitaka K, Sutani A, Isobe T. Tsubata Y, et al. Geriatr Gerontol Int. 2021 Oct;21(10):881-886. doi: 10.1111/ggi.14243. Epub 2021 Aug 10. Geriatr Gerontol Int. 2021. PMID: 34378299 Free PMC article. Clinical Trial.
The difference between dacomitinib and afatinib in effectiveness and safety in first-line treatment of patients with advanced EGFR-mutant non-small cell lung cancer: a real-world observational study.
Cheng WC, Lin CC, Liao WC, Lin YC, Chen CH, Chen HJ, Tu CY, Hsia TC. Cheng WC, et al. BMC Cancer. 2024 Feb 19;24(1):228. doi: 10.1186/s12885-024-11956-w. BMC Cancer. 2024. PMID: 38373960 Free PMC article.
Targeted Therapy for Older Patients with Non-Small Cell Lung Cancer: Systematic Review and Guidelines from the French Society of Geriatric Oncology (SoFOG) and the French-Language Society of Pulmonology (SPLF)/French-Language Oncology Group (GOLF).
Greillier L, Gauvrit M, Paillaud E, Girard N, Montégut C, Boulahssass R, Wislez M, Pamoukdjian F, Corre R, Cabart M, Caillet P, Belaroussi Y, Frasca M, Noize P, Wang P, Mebarki S, Mathoulin-Pelissier S, Couderc AL. Greillier L, et al. Cancers (Basel). 2022 Feb 2;14(3):769. doi: 10.3390/cancers14030769. Cancers (Basel). 2022. PMID: 35159036 Free PMC article. Review.
Factors associated with prolonged progression-free survival of patients treated with first-line afatinib for advanced epidermal growth factor receptor-mutated non-small cell lung cancer.
Chiu LC, Hsu PC, Wang CC, Ko HW, Kuo SC, Ju JS, Tung PH, Huang AC, Yang CT. Chiu LC, et al. Thorac Cancer. 2024 Mar;15(7):529-537. doi: 10.1111/1759-7714.15212. Epub 2024 Jan 26. Thorac Cancer. 2024. PMID: 38279515 Free PMC article.
A Phase II Trial on Osimertinib as a First-Line Treatment for EGFR Mutation-Positive Advanced NSCLC in Elderly Patients: The SPIRAL-0 Study.
Chihara Y, Takeda T, Goto Y, Nakamura Y, Tsuchiya-Kawano Y, Nakao A, Onoi K, Hibino M, Fukuda M, Honda R, Yamada T, Taniguchi R, Sakamoto S, Date K, Nagashima S, Tanzawa S, Minato K, Nakatani K, Izumi M, Shimose T, Kishimoto J, Uchino J, Takayama K. Chihara Y, et al. Oncologist. 2022 Nov 3;27(11):903-e834. doi: 10.1093/oncolo/oyac193. Oncologist. 2022. PMID: 36181763 Free PMC article. Clinical Trial.

See all "Cited by" articles

References

1. Wu YL, Planchard D, Lu S, Sun H, Yamamoto N, Kim DW, et al. Pan-Asian adapted clinical practice guidelines for the management of patients with metastatic non-small-cell lung cancer: a CSCO-ESMO initiative endorsed by JSMO, KSMO, MOS, SSO and TOS. Ann Oncol. 2019;30(2):171–210. doi: 10.1093/annonc/mdy554. - DOI - PubMed
1. National Cancer Institute. Surveillance, epidemiology and end results (SEER) stat fact sheets: lung and bronchus cancer. Available at: http://seer.cancer.gov/statfacts/html/lungb.html (Accessed 30 October 2020).
1. Wu YL, Sequist LV, Tan EH, Geater SL, Orlov S, Zhang L, et al. Afatinib as first-line treatment of older patients with EGFR mutation-positive non-small-cell lung cancer: subgroup analyses of the LUX-Lung 3, LUX-Lung 6, and LUX-Lung 7 trials. Clin Lung Cancer. 2018;19(4):e465–ee79. doi: 10.1016/j.cllc.2018.03.009. - DOI - PubMed
1. Zhang YL, Yuan JQ, Wang KF, Fu XH, Han XR, Threapleton D, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48):78985–78993. doi: 10.18632/oncotarget.12587. - DOI - PMC - PubMed
1. Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl Lung Cancer Res. 2015;4(1):36–54. - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations
Medical
- MedlinePlus Health Information
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

[1] Wu YL, Planchard D, Lu S, Sun H, Yamamoto N, Kim DW, et al. Pan-Asian adapted clinical practice guidelines for the management of patients with metastatic non-small-cell lung cancer: a CSCO-ESMO initiative endorsed by JSMO, KSMO, MOS, SSO and TOS. Ann Oncol. 2019;30(2):171–210. doi: 10.1093/annonc/mdy554. - DOI - PubMed

[2] Wu YL, Planchard D, Lu S, Sun H, Yamamoto N, Kim DW, et al. Pan-Asian adapted clinical practice guidelines for the management of patients with metastatic non-small-cell lung cancer: a CSCO-ESMO initiative endorsed by JSMO, KSMO, MOS, SSO and TOS. Ann Oncol. 2019;30(2):171–210. doi: 10.1093/annonc/mdy554. - DOI - PubMed

[3] National Cancer Institute. Surveillance, epidemiology and end results (SEER) stat fact sheets: lung and bronchus cancer. Available at: http://seer.cancer.gov/statfacts/html/lungb.html (Accessed 30 October 2020).

[4] National Cancer Institute. Surveillance, epidemiology and end results (SEER) stat fact sheets: lung and bronchus cancer. Available at: http://seer.cancer.gov/statfacts/html/lungb.html (Accessed 30 October 2020).

[5] Wu YL, Sequist LV, Tan EH, Geater SL, Orlov S, Zhang L, et al. Afatinib as first-line treatment of older patients with EGFR mutation-positive non-small-cell lung cancer: subgroup analyses of the LUX-Lung 3, LUX-Lung 6, and LUX-Lung 7 trials. Clin Lung Cancer. 2018;19(4):e465–ee79. doi: 10.1016/j.cllc.2018.03.009. - DOI - PubMed

[6] Wu YL, Sequist LV, Tan EH, Geater SL, Orlov S, Zhang L, et al. Afatinib as first-line treatment of older patients with EGFR mutation-positive non-small-cell lung cancer: subgroup analyses of the LUX-Lung 3, LUX-Lung 6, and LUX-Lung 7 trials. Clin Lung Cancer. 2018;19(4):e465–ee79. doi: 10.1016/j.cllc.2018.03.009. - DOI - PubMed

[7] Zhang YL, Yuan JQ, Wang KF, Fu XH, Han XR, Threapleton D, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48):78985–78993. doi: 10.18632/oncotarget.12587. - DOI - PMC - PubMed

[8] Zhang YL, Yuan JQ, Wang KF, Fu XH, Han XR, Threapleton D, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48):78985–78993. doi: 10.18632/oncotarget.12587. - DOI - PMC - PubMed

[9] Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl Lung Cancer Res. 2015;4(1):36–54. - PMC - PubMed

[10] Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl Lung Cancer Res. 2015;4(1):36–54. - PMC - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

A phase II study of first-line afatinib for patients aged ≥75 years with EGFR mutation-positive advanced non-small cell lung cancer: North East Japan Study Group trial NEJ027

Affiliations

A phase II study of first-line afatinib for patients aged ≥75 years with EGFR mutation-positive advanced non-small cell lung cancer: North East Japan Study Group trial NEJ027

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials

Miscellaneous

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials

Miscellaneous