臨床研究等提出・公開システム

First-line afatinib in patients aged 75 or older with advanced non-squamous non-small cell lung cancer harboring EGFR mutations; non-randomized phase II trial (NEJ027)

First-line afatinib for elderly patients (NEJ027)

38

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), 15 (39%) patients were male, all patients had an Eastern Cooperative Oncology group performance status of 0 (55.3%) or 1 (44.7%), and 61% had Del19-positive disease. In clinical stages, 37 patients (97.4%) had stage IV or post-operative recurrence.

The study was scheduled to begin in September 2015, but the first case was registered on January 28, 2016, and the enrollment pace was slower than originally planned, so the study period was extended by one year until March 2020. Registration of final case was on September 14, 2017. All enrolled patients received afatinib, but one was excliede from efficacy analysis set due to the lack of evaluable target lesion by extramural review board.

All patients had treatment-related adverse events (TRAEs), Grade 3 or 4 TRAEs were reported in 28 patients (74%); the most common were diarrhoea (11 [29%]), paronychia (9 [23.7%], rash/acne (6 [15.8%]), stomatitis (5 [13.2%]) appetite loss (5 [13.2%]) and pneumonitis (2 [5.3%]). There was no treatment-related death (TRD, Grade 5).

Overall Response Rate ; ORR The ORR was 75% [95% CI 57.8-87.9] overall and was not markedly different in patients with EGFR Del19- versus L858R-positive tumours (71.4% vs 80.0%). Primary endpoint was met. The ORR was not markedly different in patients with EGFR Del19- versus L858R-positive tumours (71.4% vs 80.0%). The disease control rate (DCR) was also similar between these patient subgroups (85.7% vs 93.3%). Progression Free Survival ; PFS Median PFS was 14.2 months [95% CI 9.5-19.0]. 1 year and 2 years PFS rate was 57.3% and 18.8%. In each EGFR mutation types, the median PFS were 18.2 months in the ex19 deletion, 12.9 months in ex21 L858R. Time to Treatment Failure ; TTF The median TTF was 18.7 months [95% CI 10.6-22.5]. 1 year and 2 years TTF rate was 64.9% and 29.7%. In each EGFR mutation types, the median TTF was 18.6 months in the ex19 deletion, 19.2 months in ex21 L858R. Overall Survival ; OS The median OS was 35.2 months [95% CI 35.2-not reach]. 1 year and 2 years OS rate were 83.8% and 78.3%. In each EGFR mutation types, the median OS were not reached in the ex19 deletion, 35.2 months in ex21 L858R.

First-line afatinib administered as a starting dose of 40 mg was well tolerated with dose adjustments and was associated with encouraging activity in Japanese patients aged 75 years or older with EGFR mutation-positive NSCLC.

Mar. 01, 2021

Mar. 01, 2021

https://bmccancer.biomedcentral.com/articles/10.1186/s12885-021-07861-1

No

N/A

https://jrct.niph.go.jp/latest-detail/jRCTs031180136

Gemma Akihiko

Nippon medical school hospital

1-1-5, Sendagi, Bunkyo-ku, Tokyo, Japan

agemma@nms.ac.jp

Minegishi Yuji

Nippon medical school hospital

1-1-5, Sendagi, Bunkyo-ku, Tokyo, Japan

+81-3-3822-2131

yminegis@nms.ac.jp

Complete

Sept. 01, 2015

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Histologically or cytological confirmed stage III/IV non-small cell lung cancer
2. Patients having EGFR mutation (exon 19 deletion or L858R)
3. No prior chemotherapy and no prior treatment with EGFR targeting small molecules or antibodies.
4. Measurable lesion for RECIST(ver 1.1)
5. Patients aged 75 years or older
6. ECOG performance status 0 to1
7. Adequate organ function
8. Life expectancy more than three months
9. Written informed consent

1. Chemotherapy, biological therapy or investigational agents for other carcinomas within four weeks prior to the start of study treatment. Hormonal treatment within 2 weeks prior to start of study treatment
2. Previous radiotherapy to the primary tumor or mesurable lesion
3. Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study
4. Patients with active lung disease such as interstitial pneumonia, active radiation pneumonitis, or drug-induced pneumonitis
5. Massive pleural or pericardial effusion, or ascites
6. Symptomatic brain metastases
7. Any history or presence of poorly controlled diseases that could affect the absorption of the study drug
8. Active infection, active hepatitis B infection, active hepatitis C infection and/or known HIV carrier.
9. Other concurrent active malignancy
10. Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug
11. Pregnancy
12. Clinically significant phycological problem
13. Patients with uncontrollable complications
14. Known hypersensitivity to afatinib or the excipients of any of the trial drugs

Both

patients aged 75 or older with advanced non-squamous non-small cell lung cancer harboring EGFR mutat

Afatinib 40mg/body daily oral administration

Overall Response Rate

Progression Free Survival
Time to Treatment Failure
Overall Survival
Disease Control Rate
1 and 2 Year Survival Rate
Adverse Event

+81-3-5802-8202

Jan. 31, 2019

none