Case Report: Dacomitinib May Not Benefit Patients Who Develop Rare Compound Mutations After Later-Line Osimertinib Treatment

Li, Hong‐Shuai; Gao, Yang; Wang, Yan

doi:10.3389/fonc.2021.649843

Cited by 10 publications

(10 citation statements)

References 23 publications

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“…Unlike a previous case report which showed that dacomitinib, the second-generation TKI, did not benefit a patient who developed mutations after later-line osimertinib treatment ( 22 ), the present case with ERBB2 mutations showed a different outcome. This patient also had mutations in TP53, a gene that is essential for DNA repair.…”

Section: Discussioncontrasting

confidence: 99%

Olaparib Combined With Dacomitinib in Osimertinib-Resistant Brain and Leptomeningeal Metastases From Non-Small Cell Lung Cancer: A Case Report and Systematic Review

Zhang

Wang

et al. 2022

Front. Oncol.

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Lung cancer patients with brain and leptomeningeal metastases usually have poor prognosis. For those patients with EGFR mutations, osimertinib, a third-generation tyrosine kinase inhibitor (TKI), is the first choice of treatment. However, drug resistance to osimertinib frequently occurs; and to date, the available follow-up treatment strategies have limited efficacy. In this case study, we report that treatments with olaparib, a Poly (ADP-ribose) polymerase (PARP) inhibitor, combined with dacomitinib, a second-generation EGFR TKI, benefited a lung cancer patient with osimertinib-resistant brain and leptomeningeal metastases. This 55-year-old male patient was found to have a pL858R mutation on EGFR exon 21 combined with TP53 and ERBB2 mutations after developing drug resistance to osimertinib treatment. Based on the genetic testing results, he was treated with olaparib and dacomitinib, and obtained 6 months of progression-free survival (PFS) and 13 months of overall survival (OS) after the diagnosis of leptomeningeal metastasis. This case report represents the first study applying PARP inhibitor in combination with dacomitinib in the treatment of leptomeningeal metastases after osimertinib resistance.

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Section: Discussioncontrasting

confidence: 99%

Olaparib Combined With Dacomitinib in Osimertinib-Resistant Brain and Leptomeningeal Metastases From Non-Small Cell Lung Cancer: A Case Report and Systematic Review

Zhang

Wang

et al. 2022

Front. Oncol.

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“…Conversely, data on the activity of dacomitinib on compound EGFR mutations are scant: despite initial signals of activity in vitro on acquired compound mutations after osimertinib resistance, no clinical activity was confirmed in this setting, so far [ 48 ].…”

Section: Resultsmentioning

confidence: 99%

Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence

et al. 2022

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Compound epidermal growth factor receptor (EGFR) mutations represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations. We conducted a systematic review to investigate the available data on this patients’ subgroup. Overall, we found a high heterogeneity in the incidence of compound mutations (4–26% of total EGFR mutant cases), which is dependent on the different testing methods adopted and the specific mutations considered. In addition, the relative incidence of distinct compound subclasses identified is reported with extreme variability in different studies. Preclinical and clinical data, excluding de novoEGFR exon 20 p.T790M compound mutations, show good responses with EGFR tyrosine kinase inhibitors (TKIs) (combined common mutations: response rate (RR) ≥ 75% with either first- or second-generation TKIs; combined common plus uncommon: RR 40–80% and 100% with first-generation TKIs and afatinib, respectively; combined uncommon: RR 20–70%, ~80% and ~75% with first-generation TKIs, afatinib and osimertinib, respectively). Overall, data are consistent in supporting the use of EGFR TKIs in treating compound EGFR mutations, taking into account different sensitivity profile of accompanying EGFR mutations for selecting the most adequate EGFR TKI for individual patients.

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“…In the future, more intensive clinical experimental studies are needed to prove the efficacy of afatinib on account of the rarity of cases. Other second-generation EGFR-TKI Dacomitinib may be ineffective in patients with L718Q/V mutation providing PFS of only 1 months in three patient [ 21 ]. In addition, there is currently no relevant research that explores whether the occurrence of L718Q/V will affect the prognosis of the patient – in other words, future research should investigate whether the mutation is a marker of poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

L718Q/V mutation in exon 18 of EGFR mediates resistance to osimertinib: clinical features and treatment

Qin

Xie

et al. 2022

Discov Onc

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Osimertinib, a mutant-specific third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is emerging as the preferred first-line of treatment for EGFR-mutant lung cancer. However, osimertinib resistance inevitably develops among patients treated with the drug. The modal resistance mechanisms of osimertinib include the occurrence of epithelial transition factor (c-MET) amplification and C797S mutation, whereas rare mutations are presented as case reports. Recently, the L718Q/V mutation in exon 18 of EGFR has been reported to contribute to one of the possible mechanisms of resistance. The clinical features and subsequent treatment strategies for this mutation require further research. This study retrospectively enrolled NSCLC patients with the L718Q/V mutation from 2017 to 2021 at the Cancer Hospital of the University of the Chinese Academy of Sciences (Zhejiang Cancer Hospital), as well as additional patients with the same mutation from PubMed literature, to summarize the clinical features of the mutation. The association between the detection of L718Q/V and resistance to osimertinib, as well as impacts on the therapeutic process and outcome, was analyzed. We included a total of two patients diagnosed at Zhejiang Cancer Hospital and twelve patients from the literature. Of the fourteen total patients, 64.3% were male and 35.7% were female. The average age of the group was 60.2 years (range 45–72). A history of tobacco use was common among the group. In all of the cases we considered, the L718Q/V mutation was secondary to the L858R mutation. The second-generation TKI afatinib was found to provide a high disease control rate (DCR) (85.7%, 6/7) and relatively low objective response rate (ORR) (42/9%, 3/7). The median progression free survival (mPFS) for this treatment reached 2 months (1–6 months). The patients failed to benefit from chemotherapy combined with immunotherapy or other TKI medications. Due to the limited number of cases considered in this study, future studies should explore drugs that more precisely target the L718Q/V mutation of EGFR exon 18.

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Case Report: Dacomitinib May Not Benefit Patients Who Develop Rare Compound Mutations After Later-Line Osimertinib Treatment

Cited by 10 publications

References 23 publications

Olaparib Combined With Dacomitinib in Osimertinib-Resistant Brain and Leptomeningeal Metastases From Non-Small Cell Lung Cancer: A Case Report and Systematic Review

Olaparib Combined With Dacomitinib in Osimertinib-Resistant Brain and Leptomeningeal Metastases From Non-Small Cell Lung Cancer: A Case Report and Systematic Review

Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence

L718Q/V mutation in exon 18 of EGFR mediates resistance to osimertinib: clinical features and treatment

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