Response to Osimertinib in a Patient With Non-Small Cell Lung Cancer and Two Uncommon EGFR mutations

Astaras, Christoforos; Bettini, Adrienne; Prof, Daniel C. Betticher

doi:10.36000/hbt.oh.2020.03.011

Cited by 2 publications

(3 citation statements)

References 8 publications

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“…64 Astaras et al presented a patient with complex EGFR mutations in exon 21 (L833V + H835F), showing a response to osimertinib with a PFS of 9 months. 65 Because of the limited number of patients with complex EGFR mutations, the efficacy of osimertinib in this group of patients warrants future study.…”

Section: Discussionmentioning

confidence: 99%

The effectiveness of afatinib in patients with lung adenocarcinoma harboring complex epidermal growth factor receptor mutation

Yang

et al. 2020

Ther Adv Med Oncol

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Background and aims: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are effective against classical EGFR mutations in lung cancer. However, their effectiveness and the prognosis of lung cancer patients with complex EGFR mutations are not well delineated. Therefore, we aimed to investigate the treatment effectiveness of different EGFR TKIs in patients with complex EGFR mutations. Patients and methods: From 2005 to 2020, we collected lung adenocarcinoma tissue samples for EGFR mutation analysis using direct Sanger sequencing. Patients with EGFR mutations treated with EGFR TKIs as first-line treatment were enrolled. Clinical characteristics, EGFR mutation status, treatment response, progression-free survival (PFS), and overall survival (OS) were analyzed. Results: Among 2675 patients with EGFR mutations, 239 (8.9%) had complex EGFR mutations, of whom 125 received EGFR TKI treatment as first-line treatment. Multivariate analysis revealed that afatinib was a more favorable factor for PFS than gefitinib [hazard ratio (HR), 2.01; 95% confidence interval (CI), 1.11–3.62] and erlotinib (HR, 2.61; 95% CI, 1.31–5.22), especially in patients with uncommon mutation patterns. Afatinib treatment as first-line treatment was also associated with longer OS compared with erlotinib (HR, 2.48; 95% CI, 1.20–5.12). Classical mutation pattern was associated with longer PFS ( p = 0.001) and OS ( p = 0.020). Secondary T790M was detected in 22 of 52 (42.3%) patients who had re-biopsied tissue samples after acquiring resistance to EGFR TKIs. There was no significant difference in secondary T790M formation after acquired resistance to the three EGFR TKIs ( p = 0.261). Furthermore, three (5.8%) patients had small-cell lung cancer transformation. Conclusion: Afatinib is an effective first-line treatment for patients with lung adenocarcinoma harboring complex EGFR mutations, especially those with uncommon mutation patterns.

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Section: Discussionmentioning

confidence: 99%

The effectiveness of afatinib in patients with lung adenocarcinoma harboring complex epidermal growth factor receptor mutation

Yang

et al. 2020

Ther Adv Med Oncol

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“…Lung adenocarcinomas with common EGFR mutations are often responsive to EGFR TKIs, while uncommon and compound mutations react unpredictably. Approximately 40-45% of EGFR mutations possess an exon 21 L858R substitution (1,3). L858R/L833V is a rare compound mutation found in 6% of lung adenocarcinoma EGFR mutation cases (2).…”

Section: Discussionmentioning

confidence: 99%

“…L858R and del 19 are called "common mutations"; they account for up to 90% of EGFR mutations in NSCLC (2). The presence of a common mutation correlates with an improved overall response rate of EGFR-TKIs, specifically osimertinib in the aforementioned study (3). Osimertinib, an irreversible, thirdgeneration EGFR-TKI, targets the Thr790Met resistance mutation as well as another common EGFR sensitizing mutations.…”

Section: Introductionmentioning

confidence: 99%

Overcoming CEP85L-ROS1, MKRN1-BRAF and MET amplification as rare, acquired resistance mutations to Osimertinib

et al. 2023

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Lung cancer is the most common cancer-related cause of death worldwide, most of which are non-small cell lung cancers (NSCLC). Epidermal growth factor receptor (EGFR) mutations are common drivers of NSCLC. Treatment plans for NSCLC, specifically adenocarcinomas, rely heavily on the presence or absence of specific actionable driver mutations. Liquid biopsy can guide the treatment protocol to detect the presence of various mechanisms of resistance to treatment. We report three NSCLC EGFR mutated cases, each treated with Osimertinib in a combination therapy regimen to combat resistance mechanisms. The first patient presented with EGFR L858R/L833V compound mutation with MET amplification alongside CEP85L-ROS1 fusion gene, the second with EGFR exon 19del and MKRN1-BRAF fusion, and the last EGFR L858R/V834L compound mutation with MET amplification. Each regimen utilized a tyrosine kinase inhibitor or monoclonal antibody in addition to osimertinib and allowed for a prompt and relatively durable treatment response.

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Response to Osimertinib in a Patient With Non-Small Cell Lung Cancer and Two Uncommon EGFR mutations

Cited by 2 publications

References 8 publications

The effectiveness of afatinib in patients with lung adenocarcinoma harboring complex epidermal growth factor receptor mutation

The effectiveness of afatinib in patients with lung adenocarcinoma harboring complex epidermal growth factor receptor mutation

Overcoming CEP85L-ROS1, MKRN1-BRAF and MET amplification as rare, acquired resistance mutations to Osimertinib

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