Real-World Characteristics and Outcomes of Advanced Non-Small-Cell Lung Cancer Patients with
            <i>EGFR</i>
            Exon 19 Deletions or Exon 21 Mutations

Winfree, Katherine B.; Molife, Cliff; Peterson, Patrick; Chen, Yongmei; Visseren‐Grul, Carla; Leusch, Mark S.; Beyrer, Julie; Dimou, Anastasios

doi:10.2217/fon-2021-0218

Cited by 12 publications

(6 citation statements)

References 32 publications

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“…The survival analysis showed that the prognosis of targeted therapy was better than chemotherapy in patients with EGFR mutant type, which was consistent with previous studies ( 43 , 44 ). However, there is no significant difference in survival time between patients with E19 and E21, furthermore, the survival rate of patients with E19 was better than that with E21, which was similar to previous study ( 45 ).…”

Section: Discussionsupporting

confidence: 90%

“…Exon 19 deletion (E19) and exon 21 L858R missense (E21) are the two most common EGFR-TKIs-sensitive EGFR mutation subtypes. There is a difference in treatment strategy, response and prognosis between patients with EGFR E19 and E21 ( 4 , 5 ). Therefore, identifying EGFR mutation status and subtypes are important for the treatment of patients with lung adenocarcinoma.…”

Section: Introductionmentioning

confidence: 99%

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Optimal 18F-FDG PET/CT radiomics model development for predicting EGFR mutation status and prognosis in lung adenocarcinoma: a multicentric study

Zuo

Liu

et al. 2023

Front. Oncol.

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PurposeTo develop and interpret optimal predictive models to identify epidermal growth factor receptor (EGFR) mutation status and subtypes in patients with lung adenocarcinoma based on multicentric 18F-FDG PET/CT data, and further construct a prognostic model to predict their clinical outcome.MethodsThe 18F-FDG PET/CT imaging and clinical characters of 767 patients with lung adenocarcinoma from 4 cohorts were collected. Seventy-six radiomics candidates using cross-combination method to identity EGFR mutation status and subtypes were built. Further, Shapley additive explanations and local interpretable model-agnostic explanations were used for optimal models’ interpretation. Moreover, in order to predict the overall survival, a multivariate Cox proportional hazard model based on handcrafted radiomics features and clinical characteristics was constructed. The predictive performance and clinical net benefit of the models were evaluated via area under receiver operating characteristic (AUC), C-index and decision curve analysis. ResultsAmong the 76 radiomics candidates, light gradient boosting machine classifier (LGBM) combined with recursive feature elimination wrapped LGBM feature selection method achieved best performance in predicting EGFR mutation status (AUC reached 0.80, 0.61, 0.71 in the internal test cohort and two external test cohorts, respectively). And extreme gradient boosting classifier combined with support vector machine feature selection method achieved best performance in predicting EGFR subtypes (AUC reached 0.76, 0.63, 0.61 in the internal test cohort and two external test cohorts, respectively). The C-index of the Cox proportional hazard model achieved 0.863.ConclusionsThe integration of cross-combination method and the external validation from multi-center data achieved a good prediction and generalization performance in predicting EGFR mutation status and its subtypes. The combination of handcrafted radiomics features and clinical factors achieved good performance in predicting prognosis. With the urgent needs of multicentric 18F-FDG PET/CT trails, robust and explainable radiomics models have great potential in decision making and prognosis prediction of lung adenocarcinoma.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Optimal 18F-FDG PET/CT radiomics model development for predicting EGFR mutation status and prognosis in lung adenocarcinoma: a multicentric study

Zuo

Liu

et al. 2023

Front. Oncol.

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“…As also previously reported [ 31 , 48 ], TP53 co-mutations were generally not associated with other measured prognostic factors (e.g., age, sex, smoking status, ECOG PS, baseline brain metastases), EGFR mutation subtype, or treatment assignment. Lastly, consistent with guideline recommendations [ 7 , 8 ] and prior studies [ 53 ], most patients with EGFR -mutated aNSCLC received EGFR -TKI monotherapy (predominantly osimertinib) in the 1 L and 2 L settings in current study, with few patients receiving 1 L EGFR -TKI combinations with either anti-angiogenics or chemotherapy.…”

Section: Discussionsupporting

confidence: 78%

“…In line with previous studies linking a TP53 co-mutation with reduced sensitivity to EGFR -TKIs [ 29 , 49 ], a TP53 co-mutation was associated with worse outcomes in the current dataset, even after adjustment for known aNSCLC prognostic factors including age, sex, smoking history, performance status, and baseline brain or bone metastases. Our findings also suggest that TP53 co-mutations in the context of the EGFR mutation subtype may impact response to treatment and the survival outcomes, as the negative survival effect associated with TP53 co-mutations has been observed to occur less among patients with EGFR exon 19 deletions than exon 21L858R mutations [ 31 , 32 ] and is likely because EGFR exon 19 deletions are known to be more responsive to EGFR -TKIs [ 53 , 54 ], as also demonstrated by our results. Notably, this finding appears to be driven by the robust OS in patients with TP53 wild-type tumors plus the exon 19 deletion subgroup (47.1 months), as the OS was similar between the exon 19 deletion subgroup plus a TP53 co-mutation (25.6 months) and an exon 21L858R mutation plus the TP53 co-mutation subgroup (28.7 months).…”

Section: Discussionmentioning

confidence: 94%

TP53 Co-Mutation Status Association with Clinical Outcomes in Patients with EGFR-Mutant Non-Small Cell Lung Cancer

Molife

Leusch

et al. 2022

Cancers

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TP53 co-mutations have shown association with poor prognosis in various solid tumors. For EGFR-mutated advanced non-small cell lung cancer (aNSCLC), conflicting results exist regarding its impact on survival. Clinical outcomes and genomic data were obtained retrospectively from the real-world (rw) de-identified clinicogenomic database. Patients who initiated therapy for EGFR-mutated aNSCLC between January 2014 and December 2020 were identified. Clinical outcomes were evaluated by TP53-mutational status. In 356 eligible EGFR-mutated aNSCLC patients (median age 68 years), 210 (59.0%) had TP53 co-mutation and 146 (41.0%) had TP53 wild-type tumor. Unadjusted analysis showed significantly shorter survival in patients with TP53 co-mutation versus TP53 wild-type (rw progression-free survival [rwPFS]: HR = 1.4, 95% CI 1.1–1.9, p = 0.0196; overall survival [OS]: HR = 1.6, 95% CI 1.1–2.2, p = 0.0088). Multivariable analysis confirmed independent association between TP53 co-mutation and worse rwPFS (HR = 1.4, 95% CI 1.0–0.9, p = 0.0280) and OS (HR = 1.4, 95% CI 1.0–2.0, p = 0.0345). Directionally consistent findings were observed for response rates, and subgroups by EGFR-activating mutation and first-line (1 L) therapy, with more pronounced negative effect in 1 L EGFR-TKI subgroup. TP53 co-mutations negatively affected survival in patients with EGFR-mutated aNSCLC receiving standard 1 L therapy in real-world practice.

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“…Additionally, the independent factors for PFS prolongation were exon 21 L858R and dose reduction within 6 months. Generally, exon 19 deletion is associated with greater antitumor efficacy of EGFR-TKIs than exon 21 L858R [ 19 ]. PD-L1 TPS ≥ 50% is a poor prognostic factor for osimertinib therapy [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of early dose reduction of osimertinib on efficacy in the first-line treatment for EGFR-mutated non-small cell lung cancer

Hori,

Yamamoto,

Ito

et al. 2024

Invest New Drugs

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SummaryOsimertinib is used as the first-line therapy for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, early dose reduction is often required due to adverse events (AEs). This study aimed to evaluate the effect of early dose reduction of osimertinib on efficacy and safety. This was a retrospective study including patients with EGFR-mutated NSCLC who were started on osimertinib as the first-line therapy between August 2018 and December 2021. Patients whose doses were reduced to less than 80 mg/day within 6 months of osimertinib initiation or started at 40 mg/day were defined as the dose reduction group. The primary endpoint was progression-free survival (PFS). Factors affecting PFS were explored using the Cox proportional hazards model. A total of 85 patients were included in this study. No significant differences in patient characteristics were observed between the dose reduction (n = 25) and standard dose groups (n = 60). The median PFS in the dose reduction group was significantly prolonged compared with that in the standard dose group (26.0 months vs. 12.0 months, p = 0.03). Multivariable analysis of 84 patients, excluding a patient with unknown brain metastasis, revealed that EGFR exon 21 L858R mutation, malignant pleural effusion or pleural metastasis, liver metastasis, and dose reduction within 6 months were independent factors affecting PFS. Early dose reduction of osimertinib is an effective therapeutic strategy for prolonging PFS in patients with EGFR-mutated NSCLC.

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Real-World Characteristics and Outcomes of Advanced Non-Small-Cell Lung Cancer Patients with EGFR Exon 19 Deletions or Exon 21 Mutations

Cited by 12 publications

References 32 publications

Optimal 18F-FDG PET/CT radiomics model development for predicting EGFR mutation status and prognosis in lung adenocarcinoma: a multicentric study

Optimal 18F-FDG PET/CT radiomics model development for predicting EGFR mutation status and prognosis in lung adenocarcinoma: a multicentric study

TP53 Co-Mutation Status Association with Clinical Outcomes in Patients with EGFR-Mutant Non-Small Cell Lung Cancer

Effect of early dose reduction of osimertinib on efficacy in the first-line treatment for EGFR-mutated non-small cell lung cancer

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