A phase II study of afatinib treatment for elderly patients with previously untreated advanced non-small-cell lung cancer harboring EGFR mutations

Imai, Hisao; Kaira, Kyoichi; Suzuki, Kensuke; Awata, Masaki; Tsuda, Takeshi; Ishizuka, Tamotsu; Kuwako, Tomohito; Nemoto, Kenji; Uchino, Junichi; Morozumi, Nobutoshi; Ishihara, Shinichi; Minato, Koichi; Hisada, Takeshi

doi:10.1016/j.lungcan.2018.10.014

Cited by 47 publications

(53 citation statements)

References 36 publications

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“…Clinical activity of afatinib with respect to response and other e cacy outcomes (PFS and OS) was encouraging, consistent with other studies in elderly Japanese patients treated with afatinib in the same setting. 19,20 E cacy outcomes were also similar in patients with EGFR Del19-and L858R-postive tumours, as reported previously. 20 The safety pro le of afatinib was as expected from EGFR TKI treatment in elderly Japanese patients, 13,20,23 and was manageable with dose reductions.…”

Section: Discussionsupporting

confidence: 86%

“…In this study, we examined elderly patients aged ≥ 75 years (median [range] 77.5 [75-91] years); this has been identi ed previously as a relevant cut-off when considering the age at which more effective and tolerable therapies compared with chemotherapy are needed. 16,22 Baseline patient and disease characteristics were largely similar to those reported in two previous investigations of afatinib in 16 However, the frequency of patients with Del19-positive disease (61%) was slightly higher than reported in elderly patients in the other two Japanese studies (20% to 55%), 19,20 and in the LUX-Lung 7 subanalysis (37%). 16 Most patients (84%) in the current study had comorbidities, the most common being hypertension, and more than one third (34%) had baseline brain metastases.…”

Section: Discussionsupporting

confidence: 79%

“…16 In addition to evidence from the LUX-Lung studies, a phase I trial including treatment at the approved dose of 40 mg, and a phase II trial employing afatinib 30 mg support the feasibility of rst-line afatinib as a treatment option in elderly Japanese patients with EGFR mutation-positive NSCLC. 19,20 The aim of the current study was to further investigate the antitumour activity and safety pro le of daily afatinib (40 mg) in previously untreated Japanese patients aged ≥ 75 years, with EGFR mutation-positive NSCLC.…”

Section: Introductionmentioning

confidence: 99%

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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

Minegishi

Yamaguchi

Sugawara

et al. 2020

Preprint

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Background: We investigated afatinib in elderly patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC).Patients and 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. 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 III/IV 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 8 (21.1%) patients discontinued afatinib due to TRAEs. No treatment-related deaths were reported.Conclusion: First-line afatinib administered at a starting dose of 40 mg was well tolerated with dose adjustments and was associated with encouraging activity in Japanese patients aged ≥ 75 years with EGFR mutation-positive NSCLC.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).

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

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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

Minegishi

Yamaguchi

Sugawara

et al. 2020

Preprint

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“…Imai and colleagues recently reported the first study of afatinib (30 mg/day) for the elderly (70 ≤) patients harboring sensitive EGFR mutations. The median PFS was 12.9 months [19]. Our data of the PFS in elderly were 15.4 months.…”

Section: Discussionmentioning

confidence: 50%

Real-world study of afatinib in first-line or re-challenge settings for patients with EGFR mutant non-small cell lung cancer

et al. 2019

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Afatinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) for mutant nonsmall cell lung cancer (NSCLC), was approved in Japan in 2014. This study evaluated clinical outcomes of afatinib in realworld practice. Medical records of patients who received afatinib for advanced EGFR-mutant NSCLC were retrospectively reviewed. In total, 128 patients were analyzed. Seventy-six patients received afatinib as the first-line setting and 52 as the re-challenge setting (i.e., after failure of prior first-generation TKI). There was no difference in patient characteristics, such as age, sex, and PS, between the first-line and the re-challenge settings. In the first-line setting, the median progression-free survival (PFS) was 17.8 months (95% confidence interval [CI] 13.7-21.5 months). The overall survival (OS) was 39.5 months (95% CI 34.4-not reached). The response rate (RR) was 64.4%. Subset analysis indicated that patients with dose reduction showed longer PFS than those without dose reduction (18.5 months versus 7.9 months) (P = 0.016). In the re-challenge setting, the median PFS was 8.0 months (95% CI 4.9-9.5 months). The RR was 25%. Most common adverse events leading to dose modification or treatment discontinuation included diarrhea, paronychia, and oral mucositis in both settings. Interstitial lung disease occurred in 5.4% (7/128). In the real-world practice in Japan, afatinib showed comparable or better efficacy compared with that shown in previous clinical trials in both the first-line and the re-challenge settings.

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“…Furthermore, a dose reduction to 30 mg/day reduced the incidence of grade > 3 AEs . In elderly patients (age ≥ 70 years) with EGFR 19del and L858R mutation‐positive NSCLC, the efficacy and feasibility of afatinib treatment starting at 30 mg/day have been reported . Since these previous reports focused on EGFR 19del and L858R mutations, the efficiency and safety of afatinib dose reduction in other uncommon EGFR mutations has not been known.…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of an elderly patient with an uncommon L861Q epidermal growth factor receptor mutation with low‐dose afatinib: A case report

et al. 2019

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There are limited data on the clinical efficiency of afatinib in non-small cell lung cancer (NSCLC) patients with uncommon epidermal growth factor receptor (EGFR) mutations. Moreover, the efficacy and safety of afatinib in elderly patients with these mutations has not been established. Here, we describe a case of successful treatment of a patient aged >80 years with lung adenocarcinoma positive for the uncommon EGFR L861Q mutation with low-dose afatinib. An 83-year-old woman presented with cough and dyspnea. A chest computed tomography (CT) scan revealed tumors in the left upper lobe, left pleural effusion, and multiple lung metastases in both lungs. The patient was diagnosed with lung adenocarcinoma with an EGFR L861Q mutation based on cytological findings. The patient received 30 mg/day of afatinib and experienced no severe adverse events. Two weeks later, partial response was observed based on a CT scan. The results of the present case support the effectiveness and safety of lowdose afatinib in elderly patients with EGFR L861Q mutation-positive NSCLC.

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A phase II study of afatinib treatment for elderly patients with previously untreated advanced non-small-cell lung cancer harboring EGFR mutations

Cited by 47 publications

References 36 publications

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

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

Real-world study of afatinib in first-line or re-challenge settings for patients with EGFR mutant non-small cell lung cancer

Successful treatment of an elderly patient with an uncommon L861Q epidermal growth factor receptor mutation with low‐dose afatinib: A case report

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