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

Iida, Yuko; Kumasawa, Fumio; Shimizu, Tetsuo; Shintani, Yoshitaka; Takahashi, N.; Gon, Yasuhiro

doi:10.1111/1759-7714.13269

Cited by 5 publications

(4 citation statements)

References 13 publications

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“…For the elderly, 20–30 mg/day is considered to be an appropriate dose. Although most reports of low‐dose afatinib are for common mutations, there has been a study reporting that low‐dose afatinib can be safely used without reducing its efficacy in elderly patients harboring uncommon mutations 15 . In this case, an appropriate reduction in the dose of afatinib resulted in a long‐term response.…”

Section: Discussionmentioning

confidence: 96%

Long‐term response to afatinib in an elderly patient with uncommon epidermal growth factor receptor mutation‐positive lung adenocarcinoma

et al. 2021

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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are the standard treatment for patients with non‐small cell lung cancer (NSCLC) harboring EGFR mutations. Uncommon mutations, excluding exon 19 deletions and exon 21 L858R, comprise 7%–23% of EGFR mutation‐positive NSCLC. The treatment of uncommon EGFR mutation‐positive NSCLCs is controversial. Here, we present the case of an 81‐year‐old man who was diagnosed with lung adenocarcinoma cStage IVA harboring the uncommon EGFR L861Q mutation. The patient received oral afatinib treatment (40 mg/day). One month after the initiation of afatinib treatment, Common Terminology Criteria for Adverse Events version 4.0 grade 2 stomatitis was observed. It improved upon afatinib withdrawal. After 10 days of withdrawal, afatinib treatment was resumed at a reduced dose of 20 mg/day. Subsequently, the patient continued treatment with afatinib. A partial response to afatinib treatment was maintained for 49 months until primary tumor regrowth. Afatinib treatment was continued after disease progression, but the patient died of bacterial pneumonia 59 months after initiation of afatinib treatment. Several studies have previously reported a large number of compound mutations with uncommon mutations, and that compound mutation‐induced cells are most susceptible to afatinib. This suggests the efficacy of afatinib in clinical practice and that afatinib may be safely administered to elderly patients with appropriate dose reductions.

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Section: Discussionmentioning

confidence: 96%

Long‐term response to afatinib in an elderly patient with uncommon epidermal growth factor receptor mutation‐positive lung adenocarcinoma

et al. 2021

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“…Another recent case report showed the successful treatment of an 83-year-old patient with an uncommon L861Q epidermal growth factor receptor mutation. He was treated with low-dose afatinib, supporting the sensitivity of this mutation to TKI-based therapy [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…Double mutations are detected in 14 to 18% of NSCLC samples, but their clinical significance remains not clearly characterized [ 43 , 44 ]. Kim et al concluded that patients with composite EGFR mutations have poor clinical outcomes and should be closely monitored during follow-up [ 41 ]. In our study, the follow-up was available for only one patient among three carrying composite EGFR mutations.…”

Section: Discussionmentioning

confidence: 99%

Predominance of the Rare EGFR Mutation p.L861Q in Tunisian Patients with Non-Small Cell Lung Carcinoma

Abdelmaksoud‐Dammak

Ammous-Boukhris

Saadallah-Kallel

et al. 2022

Genes

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Objectives: Several new cancer therapies targeting signaling pathways involved in the growth and progression of cancer cells were developed as personalized medicine. Our study aimed to identify epidermal growth factor receptor (EGFR) mutations for TKI treatment in non-small-cell lung cancer (NSCLC) Tunisian patients. Methods: Analysis of the TKI sensitivity mutations in exons 18 to 21 of the EGFR gene and exon 15 of the B-raf gene was performed in 79 formalin fixed-paraffin embedded (FFPE) NSCLC samples using pyrosequencing. Results: EGFR mutations were detected in 34 cases among 79 (43%), with the predominance of the L861Q in exon 21 found in 35.3% of the cases (12 out of 34). Deletions in exon 19 were found in 8 cases (23.5%), and only one young male patient had the T790M mutation. Three patients harbored composite EGFR mutations (p.E746_A750del/p.L861R, p.E746_S752>V/p.S768I, and p.G719A/p.L861Q). Furthermore, the EGFR mutated status was significantly more frequent in female patients (p = 0.019), in non-smoker patients (p = 0.008), and in patients with metastasis (p = 0.044). Moreover, the B-raf V600E was identified in 5 EGFR negative patients among 39 analyzed samples (13.15%). Conclusion: The p.L861Q localized in exon 21 of the EGFR gene was the most common mutation identified in our patients (35.3%), whereas the “classic” EGFR mutations such as Del19 and p.L858R were found in 23.5% and 11.7% of the cases, respectively. Interestingly, most of p.L861X mutation-carrying patients showed good response to TKI treatment. Altogether, our findings suggest a particular distribution of the EGFR-TKIs sensitivity mutations in Tunisian NSCLC patients.

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“…Previously, it has been suggested that 40 mg was the recommended afatinib dose for first-line therapy [ 10 ]. A recent study has revealed that the PFS of the non-full-dose group was 12.8 months, while the PFS was 11.0 months for the full-dose group; however, the difference was not significant (HR: 1.3, 95% CI [0.9–2.0]) [ 42 ]. Yang et al have reported that afatinib 30 mg daily as an initial dose presents a similar response rate and PFS as an initial dose of 40 mg daily [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Afatinib in the Treatment of Advanced Non-Small-Cell Lung Cancer with EGFR Mutations: A Meta-Analysis of Real-World Evidence

Zhang

Luo

Chen

et al. 2021

Journal of Oncology

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Introduction. The purpose of this study was to explore the efficacy and safety of afatinib in advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations based on real-world evidence. Materials and Methods. Eligible real-world studies were identified from PubMed, Cochrane Library, and Embase. Cochrane guidelines were used to assess the quality of included studies. Cochran’s Q test and I2 statistics were used for the heterogeneity analysis. Results. Twenty-five studies were included in this meta-analysis; nine studies were included in the qualitative descriptive analysis. The summarized disease control rate (DCR) was 87.6% (81.5%, 92.7%), and the overall response rate (ORR) was 58.9% (48.8%, 68.7%). The pooled median progression-free survival (PFS) was 12.4 (10.3, 14.5) months, mean time to failure (TTF) was 15.4 (13.6, 17.2) months, and median overall survival (OS) was 31.6 (26.7, 36.5) months. The total incidences of adverse events (AEs) for skin rashes, diarrhea, paronychia, and mucositis were 71.4% (64.4%, 77.9%), 70.4% (60.1%, 79.8%), 52.1% (41.9, 62.3%), and 36.5% (29.5%, 43.8%), respectively. The incidences of severe adverse events (SAEs, Grade ≥3) for diarrhea, skin rashes, paronychia, and mucositis were 9.7% (6.8%, 13.1%), 5.8% (4.5%, 7.2%), 3.8% (2.0%, 6.2%), and 2.1% (1.0%, 3.6%), respectively. Differences in PFS and OS between the afatinib non-full-dose (<40 mg) and full-dose (>40 mg) groups were not significant ( P > 0.05 ). However, the ORR in the full-dose group was 78.5% (66.7%, 88.4%), which was significantly higher than that in the non-full-dose group (67.8% [56.8%, 77.9%]). Conclusion. The efficacy and safety of afatinib has been confirmed by real-world evidence in advanced NSCLC with EGFR mutation, consistent with randomized controlled trial results. In real-world setting, tolerability-guided dose adjustment might not affect the afatinib efficacy.

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

Cited by 5 publications

References 13 publications

Long‐term response to afatinib in an elderly patient with uncommon epidermal growth factor receptor mutation‐positive lung adenocarcinoma

Long‐term response to afatinib in an elderly patient with uncommon epidermal growth factor receptor mutation‐positive lung adenocarcinoma

Predominance of the Rare EGFR Mutation p.L861Q in Tunisian Patients with Non-Small Cell Lung Carcinoma

Efficacy and Safety of Afatinib in the Treatment of Advanced Non-Small-Cell Lung Cancer with EGFR Mutations: A Meta-Analysis of Real-World Evidence

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