Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer harboring uncommon EGFR mutations: Focus on afatinib

Masood, Ashiq; Kancha, Rama Krishna; Subramanian, Janakiraman

doi:10.1053/j.seminoncol.2019.08.004

Cited by 66 publications

(48 citation statements)

References 86 publications

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“…Moreover, the median PFS and OS after the subsequent osimertinib treatment were significantly shorter in patients harboring uncommon sensitive EGFR mutations compared with common mutations. Preclinical data showed that uncommon sensitive EGFR mutations displayed lower sensitivities to osimertinib compared with common mutation, with higher half-maximal inhibitory concentration (IC50) values compared with 19del or L858R [38][39][40]. Furthermore, Cho et al [41] investigated the efficacy of front-line osimertinib in 35 patients harboring uncommon sensitive mutations (including 19 with G719X, 9 with L861Q, 8 with S768I and 3 with other mutations).…”

Section: Discussionmentioning

confidence: 99%

Uncommon EGFR mutations associate with lower incidence of T790M mutation after EGFR-TKI treatment in patients with advanced NSCLC

Yang

Mao

et al. 2020

Lung Cancer

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Section: Discussionmentioning

confidence: 99%

Uncommon EGFR mutations associate with lower incidence of T790M mutation after EGFR-TKI treatment in patients with advanced NSCLC

Yang

Mao

et al. 2020

Lung Cancer

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“…In a combined post hoc analysis of three prospective trials, LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6, afatinib showed activity towards the most frequent uncommon EGFR mutations such as G719X, L861Q, and S768I, but not towards de novo T790M or exon 20 insertion mutations [39]. Additionally, second-generation EGFR-TKIs, especially afatinib, indicated broader activity across uncommon mutations compared to firstand third-generation EGFR-TKIs in preclinical studies [38,40]. Some retrospective data also support the efficacy of afatinib [38,41].…”

Section: Case Reports In Oncological Medicinementioning

confidence: 97%

“…The data regarding the efficacy of available EGFR-TKIs against NSCLC with uncommon EGFR mutations is limited, as patients with uncommon mutations were excluded from most clinical trials. Patients with uncommon mutations are a heterogeneous group with different sensitivities to different EGFR-TKIs [38]. Afatinib and osimertinib have some evidence in NSCLC with uncommon EGFR mutations.…”

Section: Case Reports In Oncological Medicinementioning

confidence: 99%

“…Additionally, second-generation EGFR-TKIs, especially afatinib, indicated broader activity across uncommon mutations compared to firstand third-generation EGFR-TKIs in preclinical studies [38,40]. Some retrospective data also support the efficacy of afatinib [38,41]. Recently, a first prospective multicentre phase II trial demonstrated osimertinib activity towards uncommon EGFR mutations.…”

Section: Case Reports In Oncological Medicinementioning

confidence: 99%

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Complete Remission of Multiple Brain Metastases in a Patient with EGFR-Mutated Non-Small-Cell Lung Cancer Treated with First-Line Osimertinib without Radiotherapy

Ameku¹,

Higa

2020

Case Reports in Oncological Medicine

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Osimertinib has demonstrated efficacy against stable or asymptomatic central nervous system (CNS) metastases of epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) in phase 2 and 3 clinical trials that allowed prior CNS radiotherapy. However, the efficacy of osimertinib only or the optimal treatment combination or sequence of radiotherapy has not been investigated. A 74-year-old woman diagnosed with T4N1M1c Stage IVB lung adenocarcinoma with EGFR mutation presented with a left upper lobe mass and multiple bilateral lung metastases. A total of more than 20 asymptomatic multiple brain metastases with a maximum diameter of 12 mm were diagnosed simultaneously. Osimertinib was administered as first-line treatment. Whole brain radiotherapy was deferred because she had no neurological symptoms. After 5 weeks, the multiple brain metastases disappeared completely, together with the response in the lung lesions. This case demonstrated that first-line treatment with osimertinib could even achieve complete remission of multiple brain metastases comprising as many as twenty lesions of EGFR-mutated NSCLC without radiation therapy. Radiation therapy for brain metastases can be deferred or even withheld. A new treatment strategy for EGFR mutated NSCLC with CNS metastases should be investigated using osimertinib, especially regarding optimal combination or sequence of radiotherapy.

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“…However, due to the low frequency of uncommon EGFR mutations and the uncertain outcomes of afatinib, the number of patients receiving afatinib in clinical practice was relatively small. The related reports are mainly small retrospective studies and case reports [17][18][19][20][21][22]. Therefore, we conducted this pooled analysis to explore the clinical characteristics of patients with uncommon EGFR mutations, as well as the e cacy and outcomes of applying afatinib, to provide a reference for clinicians to formulate treatment plans for patients with rare EGFR mutations.…”

Section: Introductionmentioning

confidence: 99%

Outcomes of Afatinib in Non-small Cell Lung Cancer Patients Harboring Uncommon Epidermal Growth Factor Receptor Mutations

Zhao¹,

Hu²,

Dong³

et al. 2020

Preprint

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Background: Uncommon epidermal growth factor receptor (EGFR) mutations are a heterogeneous population of molecular alterations, and clinical data on the outcomes of afatinib in patients with non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutations are limited. The purpose of this pooled analysis was to investigate the clinicopathological features of uncommon EGFR mutations in patients and the treatment response and survival associated with afatinib treatment.Methods: We performed a literature search in the NCBI PubMed database to identify relevant articles and completed a pooled analysis based on 37 related published studies.The relationship between clinical characteristics, EGFR mutation type and treatment response were analyzed using univariate chi-square analysis, and survival analysis was performed using the Kaplan–Meier method.Results: A total of 57 patients were included in this pooled analysis. The objective response rate to treatment with afatinib was 46.4%, with a median PFS of 7.0 months.Patients with a single uncommon EGFR mutation are more likely than patients with multiple mutations to show a good tumor response after receiving afatinib (ORR: 57.9% vs 26.3%, HR: 0.260, 95% CI: 0.078-0.869, p=0.029). Similarly, patients with a single uncommon EGFR mutation had a longer PFS than patients with multiple mutations (mPFS: 10.0 months vs 3.6 months, HR: 2.906, 95% CI: 1.496-5.646, p=0.002). In addition, for patients with a good treatment response, the PFS was also longer (HR: 2.902, 95% CI: 1.522-5.533, p=0.001).Conclusions: For patients with uncommon mutations, the outcomes of afatinib is worse than that of patients with classic sensitive mutations but higher than that of EGFR wild-type patients. Uncommon EGFR mutations contain various subtypes, and different subtypes have different sensitivities to afatinib. Patients with a single rare mutation show better treatment responses to afatinib and better prognoses than patients with multiple mutations.

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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer harboring uncommon EGFR mutations: Focus on afatinib

Cited by 66 publications

References 86 publications

Uncommon EGFR mutations associate with lower incidence of T790M mutation after EGFR-TKI treatment in patients with advanced NSCLC

Uncommon EGFR mutations associate with lower incidence of T790M mutation after EGFR-TKI treatment in patients with advanced NSCLC

Complete Remission of Multiple Brain Metastases in a Patient with EGFR-Mutated Non-Small-Cell Lung Cancer Treated with First-Line Osimertinib without Radiotherapy

Outcomes of Afatinib in Non-small Cell Lung Cancer Patients Harboring Uncommon Epidermal Growth Factor Receptor Mutations

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