&lt;p&gt;Response to Afatinib in a Patient with NSCLC Harboring Novel &lt;em&gt;EGFR&lt;/em&gt; Exon 20 Insertion Mutations&lt;/p&gt;

Li, Gang; Wu, Xiaomai; Yan, Shiyu; Zhu, Yefei; Yan, Zhengqing; Lv, Dongqing; Ge, Hongfei

doi:10.2147/ott.s268694

Cited by 8 publications

(7 citation statements)

References 18 publications

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“…[11][12][13] Nevertheless, several studies have shown durable responses to afatinib in patients who harbor exon-20ins mutations near codon 770. [14][15][16] Similarly, the efficacy of third-generation EGFR TKIs is also controversial.…”

Section: Discussionmentioning

confidence: 99%

First report of furmonertinib as a first-line treatment in advanced lung adenocarcinoma patients harboring EGFR exon 20 insertion mutations after the kinase domain αC-helix: Two case reports and a literature review

Han,

Zhang,

Liu

et al. 2023

Medicine

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Rationale: Many studies have shown that first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors are less effective in patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations. The efficacy of third-generation epidermal growth factor receptor tyrosine kinase inhibitors is still under investigation. Although new targeted tyrosine kinase inhibitors and monoclonal antibody-based agents have made significant advances in the treatment of epidermal growth factor receptor exon 20 insertion (EGFR ex20ins) mutation, the efficacy of these novel agents is not quite satisfactory. Platinum- and pemetrexed-based chemotherapy remains the standard first-line treatment for patients harboring EGFR ex20ins mutation. Patient concerns: We report for the first time 2 Chinese patients diagnosed with advanced lung adenocarcinoma with EGFR ex20ins mutations after analysis of the αC-helix sequence by next-generation sequencing. Both patients were treated with furmonertinib as the first-line therapy. Interventions: The first case included a 38-year-old female who had an EGFR ex20ins mutation (p.S768_D770dupSVD). After 1 month of treatment with furmonertinib, her symptoms of pain and cough were significantly alleviated. She achieved a partial response according to response evaluation criteria in solid tumors.[1] The final progression-free survival was 8.13 months. The second case included a 40-year-old male who had an EGFR ex20ins mutation (p.N771_P772insVal). He had a good response to furmonertinib and exhibited stable disease according to response evaluation criteria in solid tumors with a progression-free survival of 10.90 months. Outcomes: Both patients experienced significant improvement in symptoms and prolonged survival after furmonertinib was used as first-line treatment. Side effects were limited but manageable. Conclusion: The present study indicates that furmonertinib may be a first-line treatment option for patients with non-small cell lung cancer harboring EGFR ex20ins mutation.

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Section: Discussionmentioning

confidence: 99%

First report of furmonertinib as a first-line treatment in advanced lung adenocarcinoma patients harboring EGFR exon 20 insertion mutations after the kinase domain αC-helix: Two case reports and a literature review

Han,

Zhang,

Liu

et al. 2023

Medicine

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“…Consistently, the average IC50 values for afatinib and osimertinib across 6 EGFR ex20ins mutants (A767insASV, S768dupSVD, V769insASV, D770insNPG, D770insSVD, H773insNPH) were 39.9 nM and 103 nM, respectively ( 23 ). And afatinib achieved a durable response in a small number of NSCLC patients harboring specific EGFR ex20ins mutations ( 24 – 27 ). Similarly, poziotinib has a less rigid core and smaller terminal groups than osimertinib, which allows it to assess the restricted drug-binding pocket of EGFR ex20ins mutants more easily ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Osimertinib Followed by Osimertinib Plus Bevacizumab, Personalized Treatment Strategy for a Lung Cancer Patient With a Novel EGFR Exon 20 Insertion D770_N771insGT and Multiple Brain Metastases

Zhi

Luo²,

et al. 2021

Front. Oncol.

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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) are the standard of care for non–small cell lung cancer (NSCLC) patients with EGFR exon 19 deletion and L858R mutations. However, no EGFR TKI has been approved for NSCLC patients harboring insertion mutations in EGFR exon 20 (EGFRex20ins), a subgroup of uncommon EGFR mutations resistant to first-generation EGFR TKIs. This unmet clinical challenge is further complicated by disease progression due to brain metastases (BMs), which limits the use of EGFR TKIs with low intracranial activity. Osimertinib, a third-generation EGFR TKI with high CNS activity, has demonstrated superior efficacy as a first-line treatment for EGFR-mutant NSCLC with or without BM. The VEGF pathway is a key mediator of cancer metastasis and resistance to EGFR TKIs. Accumulating evidence has demonstrated that the addition of anti-VEGF agents to EGFR TKIs provides an alternative treatment option for the clinical management of EGFR-mutant NSCLC. We herein report an NSCLC case with a novel EGFRex20ins mutation D770_N771insGT and multiple brain metastases who briefly responded to first-line osimertinib treatment and subsequently achieved prolonged disease control with osimertinib plus bevacizumab as second-line treatment. Our case suggests that osimertinib in combination with bevacizumab may be an effective option for NSCLC patients with specific EGFRex20ins mutations and brain metastases.

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“…22 Case reports have described sensitivity to afatinib of H773dup, H773_V774insNPH, and N771delinsKG mutations. [23][24][25] In-frame insertions of exon 20 occur also in HER2 in approximately 1-2% of NSCLC. Exon20ins mutations of HER2 are less heterogenous than those of EGFR, with Y772dupYVMA and A775_G776insYVMA accounting for more than 80% of the cases.…”

Section: The Context Of Exon20ins Inhibitorsmentioning

confidence: 99%

Amivantamab in the Treatment of Metastatic NSCLC: Patient Selection and Special Considerations

Petrini¹,

Giaccone²

2022

OTT

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Amivantamab is a bispecific antibody that recognizes epidermal growth factor receptor (EGFR) and MET proto-oncogene (MET). In May 2021, the Food and Drug Administration gave an accelerated approval of amivantamab for the treatment of non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertions (Exon20ins) who progressed after platinum-based chemotherapy. Amivantamab prevents ligand binding to EGFR and MET and the dimerization of the receptors suppressing the downstream signal transduction. Moreover, amivantamab determines antibody dependent cellular cytotoxicity and down regulation of cell surface proteins through internalization of the receptor and trogocytosis. Preliminary results of the Phase I/IB CHRYSALIS trial demonstrated an objective response rate of 40% with a median duration of response of 11.1 months (95% CI 9.6-not reached) in 81 patients treated with amivantamab with pretreated NSCLC with Exon20ins EGFR mutations. In a different cohort of the CHRYSALIS trial, patients with Ex19del and L858R EGFR mutations were enrolled after progression on osimertinib. 121 and 45 patients received amivantamab or a combination with lazertinib, a third-generation tyrosine kinase inhibitor, respectively. The objective response rate was 19% and 36% in patients treated with amivantamab alone or in combination with lazertinib, with a median progression-free survival of 6.9 (95% CI: 3.2–5.3) and 11.1 (95% CI: 3.7–9.5) months, respectively. All 20 patients with Ex19del and L858R EGFR mutations who received amivantamab and lazertinib as their first line treatment achieved an objective response. Amivantamab is currently under evaluation in Phase III clinical trials for the first line treatment of NSCLCs with Exon20ins EGFR mutations in combination with chemotherapy (PAPILLON), for the first line therapy of Ex19del and L858R mutated NSCLCs in combination with lazertinib (MARIPOSA) and in combination with chemotherapy and lazertinib in NSCLCs who progressed on osimertinib (MARIPOSA-2).

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

Cited by 8 publications

References 18 publications

First report of furmonertinib as a first-line treatment in advanced lung adenocarcinoma patients harboring EGFR exon 20 insertion mutations after the kinase domain αC-helix: Two case reports and a literature review

First report of furmonertinib as a first-line treatment in advanced lung adenocarcinoma patients harboring EGFR exon 20 insertion mutations after the kinase domain αC-helix: Two case reports and a literature review

Case Report: Osimertinib Followed by Osimertinib Plus Bevacizumab, Personalized Treatment Strategy for a Lung Cancer Patient With a Novel EGFR Exon 20 Insertion D770_N771insGT and Multiple Brain Metastases

Amivantamab in the Treatment of Metastatic NSCLC: Patient Selection and Special Considerations

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