Successful treatment of a lung adenocarcinoma patient with a novel EGFR exon 20-ins mutation with afatinib

Cai, Yangyang; Wang, Xu; Guo, Ye; Sun, Chao; Xu, Yinghui; Qiu, Shi; Ma, Kewei

doi:10.1097/md.0000000000013890

Cited by 13 publications

(15 citation statements)

References 27 publications

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“…Only limited details regarding insertion subtype were available in this analysis. However, certain rare exon 20 insertions were documented that were sensitive to afatinib, including A767delinsASVD 39 and A767_S768insSVA. 40 Therefore, afatinib could be a treatment option against some exon 20 insertions in the future, which remains an area of unmet medical need, despite recent progress in the development of specific agents.…”

Section: May 2020mentioning

confidence: 99%

Afatinib for the Treatment of NSCLC Harboring Uncommon EGFR Mutations: A Database of 693 Cases

Yang

Schüler

Popat

et al. 2020

Journal of Thoracic Oncology

211

198

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Introduction: Limited clinical data are available regarding the efficacy of EGFR tyrosine kinase inhibitors (EGFR TKIs) in patients with NSCLC harboring uncommon EGFR mutations. This pooled analysis assessed the activity of afatinib in 693 patients with tumors harboring uncommon EGFR mutations treated in randomized clinical trials, compassionate-use and expanded-access programs, phase IIIb trials, noninterventional trials, and case series or studies. Methods: Patients had uncommon EGFR mutations, which were categorized as follows: (1) T790M; (2) exon 20 insertions; (3) "major" uncommon mutations (G719X, L861Q, and S768I, with or without any other mutation except T790M or an exon 20 insertion); (4) compound mutations; and (5) other uncommon mutations. Key end points were overall response rate (ORR), duration of response, and time to treatment failure (TTF). Results: In EGFR TKI-naive patients (n ¼ 315), afatinib demonstrated activity against major uncommon mutations (median TTF ¼ 10.8 mo; 95% confidence interval [CI]: 8.1-16.6; ORR ¼ 60.0%), compound mutations (median TTF ¼ 14.7 mo; 95% CI: 6.8-18.5; ORR ¼ 77.1%), other uncommon mutations (median TTF ¼ 4.5 mo; 95% CI: 2.9-*Corresponding author.

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Section: May 2020mentioning

confidence: 99%

Afatinib for the Treatment of NSCLC Harboring Uncommon EGFR Mutations: A Database of 693 Cases

Yang

Schüler

Popat

et al. 2020

Journal of Thoracic Oncology

211

198

View full text Add to dashboard Cite

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“…Combining the treatment data of first-generation EGFR-TKIs for the vast majority of exon 20 insertion mutations (other than A763_Y764insFQEA and V769_D770insASV), the overall response rate (ORR) was less than 10%, and the PFS was less than 3 months. [ 2 , 14 – 18 ] The response of patients with uncommon EGFR mutations to afatinib was also investigated in a prospective study. [ 13 ] In this study, the ORR was 8.7%, and the PFS was 2.7 months in the exon 20 insertion mutation group.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, other clinical trials for exon 20 insertion mutations are in progress. [ 2 ] Poziotinib has achieved a 64% ORR in a phase II clinical trial (NCT03066206), [ 6 ] and the efficacy of other EGFR-TKIs or EGFR exon 20 insertion-selective inhibitors is being evaluated. [ 18 ] We expect that these drugs will show good efficacy in patients with exon 20 insertion mutations.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with exon 19 deletions or exon 21 L858R point mutations show durable responses when treated with EGFR tyrosine kinase inhibitors (TKIs). [ 2 ] Unlike the common exon 19 deletions and exon 21 L858R point mutations, exon 20 insertions account for less than 10% of EGFR mutations in nonsmall cell lung cancer (NSCLC) patients. [ 3 ] These mutations are clustered between codons 762 and 775 and contribute to resistance to gefitinib and erlotinib (first-generation EGFR-TKIs), as well as to afatinib and dacomitinib (second-generation EGFR-TKIs).…”

Section: Introductionmentioning

confidence: 99%

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Poor effect of osimertinib on EGFR exon 20 insertion-positive lung adenocarcinoma

Inagaki¹,

Tamiya²,

Matsuda³

et al. 2020

Medicine

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Introduction: The clinical efficacy of osimertinib for patients with lung adenocarcinoma harboring epidermal growth factor receptor ( EGFR ) exon 20 insertion mutations is unclear. Few case reports exist on the successful treatment of such tumors with osimertinib. We report a case wherein osimertinib administration had no effect in a patient with EGFR exon 20 insertion-positive lung adenocarcinoma. Patient concerns: A 48-year-old never-smoking woman was referred to our hospital for chronic cough. Computed tomography (CT) and positron emission tomography-CT revealed a nodule in the right middle lobe, consolidation in the right upper lobe, multiple lymph node metastases, liver metastasis, and multiple bone metastases. Diagnosis: On the basis of further examination using transbronchial lung biopsy, the patient was diagnosed with cT1N3M1 stage IVB lung adenocarcinoma. An EGFR exon 20 insertion, without any additional mutations, was identified. Interventions: Daily oral administration of 80 mg osimertinib was initiated to treat the EGFR exon 20 insertion-positive lung adenocarcinoma. Outcomes: Although the disease appeared to be stable 2.5 months after the administration of osimertinib, the tumor started to grow 3 months after administration, and carcinoembryonic antigen levels became higher than those before treatment. Thus, osimertinib was discontinued, and treatment with carboplatin as well as pemetrexed and bevacizumab was started, which the patient responded to. Conclusion: EGFR exon 20 insertion mutations must be classified in more detail to assess the efficacy of EGFR tyrosine kinase inhibitors. Osimertinib doses that provide favorable therapeutic windows should be considered. Further clinical research is required to clarify the efficacy of osimertinib and other drugs for exon 20 insertion mutations.

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“…A patient with EGFR A767delinsASVD achieved partial response (PR) with afatinib treatment and PFS of 7.4 months. 8 Jänne et al 9 reported one patient harboring EGFR D770delinsGY, who achieved PR after dacomitinib treatment. Another patient harboring EGFR S768_D770dup could respond to osimertinib with PFS of over 5 months.…”

Section: Introductionmentioning

confidence: 99%

<p>Response to Afatinib in a Patient with NSCLC Harboring Novel <em>EGFR</em> Exon 20 Insertion Mutations</p>

Li¹,

Wu²,

Yan³

et al. 2020

OTT

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Most epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are resistant to tyrosine kinase inhibitors (TKIs). While some non-small cell lung cancer (NSCLC) patients harboring special subtypes of EGFR ex20ins still achieved clinical response after TKIs treatment, identifying special subtypes of EGFR ex20ins is helpful to find out NSCLC patients who can respond to TKIs. Case Presentation: A 71-year-old non-smoker Chinese female was diagnosed with advanced lung adenocarcinoma harboring EGFR ex20ins (N771delinsKG). The patient received first-line afatinib (40 mg/day) therapy and a significant and substantial reduction in tumor size was observed subsequently. According to RESIST 1.1, a radiological partial response was achieved. The final progression-free survival was 10 months. Conclusion: This is the first published case report of EGFR N771delinsKG lung adenocarcinoma, which highlighted the heterogeneity of clinical response to TKIs for EGFR ex20ins-mutant NSCLC. Such results need to be further investigated in prospective studies.

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Successful treatment of a lung adenocarcinoma patient with a novel EGFR exon 20-ins mutation with afatinib

Cited by 13 publications

References 27 publications

Afatinib for the Treatment of NSCLC Harboring Uncommon EGFR Mutations: A Database of 693 Cases

Afatinib for the Treatment of NSCLC Harboring Uncommon EGFR Mutations: A Database of 693 Cases

Poor effect of osimertinib on EGFR exon 20 insertion-positive lung adenocarcinoma

<p>Response to Afatinib in a Patient with NSCLC Harboring Novel <em>EGFR</em> Exon 20 Insertion Mutations</p>

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