P2.14-59 Osimertinib in EGFR T790M Advanced NSCLC: Analysis of Uncommon/Complex EGFR Mutations in a Real-World Study (ASTRIS)

Cheema, Parneet K.; Passaro, Antonio; Martin, Charles E.; Tiseo, Marcello; Park, K.; Chang, Gee‐Chen; Hu, Yang; Cho, B.C.; Miranda, Miguel; Fernandes, A.; Freitas, Helano

doi:10.1016/j.jtho.2019.08.1844

Cited by 5 publications

(4 citation statements)

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“…[29] In addition, the ASTRIS study found that osimertinib showed better efficacy in T790M positive patients with advanced NSCLC with a combination of T790M and rare/complex mutations (T790M + G719X/S768I/ex20ins or T790M + two or more mutations) than patients in full analysis set (advanced T790M positive NSCLC patients who previously received EGFR-TKI) (ORR: 50.0% vs. 57.0%; median PFS: 8.1 months vs. 11.1 months). [30] In summary, third-generation EGFR-TKIs have clinical effects on EGFR compound mutations, especially complex mutations involving T790M, while the efficacy of third-generation EGFR-TKIs in patients with other compound exon 20 mutations should be further explored.…”

Section: Egfr Compound Mutationsmentioning

confidence: 99%

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Epidermal growth factor receptor compound and concomitant mutations: advances in precision treatment strategies

Bai

Guo

et al. 2023

Chinese Medical Journal

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Epidermal growth factor receptor (EGFR) mutations are common oncogenic driver mutations in patients with non-small cell lung cancer (NSCLC). The application of EGFR-tyrosine kinase inhibitors (TKIs) is beneficial for patients with advanced and early-stage NSCLC. With the development of next-generation sequencing technology, numerous patients have been found to have more than one genetic mutation in addition to a single EGFR mutation; however, the efficacy of conventional EGFR-TKIs and the optimal treatments for such patients remain largely unknown. Thus, we review the incidence, prognosis, and current treatment regimens of EGFR compound mutations and EGFR concomitant mutations to provide treatment recommendations and guidance for patients with these mutations.

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Section: Egfr Compound Mutationsmentioning

confidence: 99%

“…11.1 months). [ 30 ] In summary, third-generation EGFR-TKIs have clinical effects on EGFR compound mutations, especially complex mutations involving T790M, while the efficacy of third-generation EGFR-TKIs in patients with other compound exon 20 mutations should be further explored.…”

Section: Egfr Compound Mutationsmentioning

confidence: 99%

Epidermal growth factor receptor compound and concomitant mutations: advances in precision treatment strategies

Bai

Guo

et al. 2023

Chinese Medical Journal

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“…Moreover, Si et al reported an even lower ORR of only 10% in 11 patients carrying the T790M mutation who were treated with osimertinib (Si et al, 2021). Additionally, the real-world study ASTRIS (NCT02474355) also concluded that patients with ucm-EGFRms containing T790M had a poorer response to osimertinib, with a lower ORR and shorter PFS (Cheema et al, 2019). In brief, for patients with multiple ucm-EGFRms that contain T790M, given the wide heterogeneity of ucm-EGFRms and the limited clinical data available, clinicians should make prudent clinical decisions based on complete comprehension of the sensitivity and resistance of known mutated genes, especially concurrent partner mutations.…”

Section: Figurementioning

confidence: 99%

Insensitivity to T790M mutation? A pooled analysis of outcomes following osimertinib for the treatment of NSCLC patients harboring uncommon epidermal growth factor receptor mutation

Wang

et al. 2022

Front. Pharmacol.

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Background: In this pooled analysis, the aim was to investigate the clinicopathological characteristics of patients with uncommon epidermal growth factor receptor (EGFR) (ucm-EGFRms) along with their treatment responses and survival following osimertinib treatment.Methods: Univariate chi-square analysis was conducted to analyze the correlation between clinical characteristics, EGFR mutation type, and treatment response, and the Kaplan-Meier method was applied for survival analysis. Univariate logistic regression model and Cox proportional hazards model were performed to compare the efficacy and prognosis in subgroup analysis.Results: Seventy-two NSCLC patients in total were included in this pooled analysis. The objective response rate (ORR) for osimertinib treatment was 57.0%, with a median PFS of 7.1 months. Twenty-eight patients received osimertinib as first-line therapy with an ORR of 67.9%, which was higher than that in patients who received osimertinib as second- or later-line therapy, and their response rate was 50%, nevertheless, no statistically significant differences were found (p = 0.139). However, patients who received first-line osimertinib showed a more significant PFS benefit than those who received second- or later-line therapy (mPFS: 16.8 months vs 6.0 months HR: 2.453, 95%CI: 1.285-4.682, p =0.004). Subgroup analysis showed that patients with a single, non-ex20ins, ucm-EGFRm displayed a superior efficacy advantage and favorable survival benefit following osimertinib treatment, with an ORR of 68.8% and an mPFS at 15.1 months. By contrast, patients with a multiple ucm-EGFRm that contain T790M exhibited the worst outcome of osimertinib treatment, with an ORR of 47.6% and an mPFS of only 3.6 months, respectively.Conclusion: Patients with um-EGFRms exhibit favorable but inconsistent responses and survival outcomes following osimertinib treatment, which is closely related to the mutation pattern and cooccurring partner mutant genes. Administering osimertinib for the treatment of patients with um-EGFRm might be considered an effective treatment option in some circumstances.

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“…Interim results of a phase ii single arm study of patients with treatment-naïve (61%) and pretreated disease demonstrated that osimertinib was active: the orr in patients with L861Q was 77.8%; with G719X, 52.8%; and with S768I, 37.5%; the median pfs was only 9.5 months (range: 1.0-20.1 months) 45 , however. The astris real-world treatment study measured outcomes in 53 patients with an acquired T790M mutation in the setting of uncommon mutations; those patients were treated with 1 or more lines of egfr tki followed by osimertinib, resulting in a median pfs of 8.1 months compared with the 11.1 months seen in the full dataset (n = 3015) 46,47 . Studies in patients with uncommon EGFR mutations who were naïve to egfr tkis are continuing (see NCT03434418 at https:// ClinicalTrials.gov/).…”

Section: Recommendation 3amentioning

confidence: 99%

Canadian Consensus: A New Systemic Treatment Algorithm for Advanced EGFR-Mutated Non-Small-Cell Lung Cancer

Melosky¹,

Banerji

Blais

et al. 2020

Current Oncology

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Background Multiple clinical trials for the treatment of advanced EGFR-mutated non-small-cell lung cancer (nsclc) have recently been reported. As a result, the treatment algorithm has changed, and many important clinical questions have been raised: ■ What is the optimal first-line treatment for patients with EGFR-mutated nsclc? ■ What is preferred first-line treatment for patients with brain metastasis? ■ What is the preferred second-line treatment for patients who received first-line first- or second-generation tyrosine kinase inhibitors (tkis)? ■ What is the preferred treatment after osimertinib? ■ What evidence do we have for treating patients whose tumours harbour uncommon EGFR mutations? Methods A Canadian expert panel was convened to define the key clinical questions, review recent evidence, and discuss and agree on practice recommendations for the treatment of advanced EGFR-mutated nsclc. Results The published overall survival results for osimertinib, combined with its central nervous system activity, have led to osimertinib becoming the preferred first-line treatment for patients with common EGFR mutations, including those with brain metastasis. Other agents could still have a role, especially when osimertinib is not available or not tolerated. Treatment in subsequent lines of therapy depends on the first-line therapy or on T790M mutation status. Treatment recommendations for patients whose tumours harbour uncommon EGFR mutations are guided mainly by retrospective and limited prospective evidence. Finally, the evidence for sequencing and combining tkis with chemotherapy, angiogenesis inhibitors, checkpoint inhibitors, and other new therapeutics is reviewed. Conclusions This Canadian expert consensus statement and algorithm were driven by significant advances in the treatment of EGFR-mutated nsclc.

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P2.14-59 Osimertinib in EGFR T790M Advanced NSCLC: Analysis of Uncommon/Complex EGFR Mutations in a Real-World Study (ASTRIS)

Cited by 5 publications

References 0 publications

Epidermal growth factor receptor compound and concomitant mutations: advances in precision treatment strategies

Epidermal growth factor receptor compound and concomitant mutations: advances in precision treatment strategies

Insensitivity to T790M mutation? A pooled analysis of outcomes following osimertinib for the treatment of NSCLC patients harboring uncommon epidermal growth factor receptor mutation

Canadian Consensus: A New Systemic Treatment Algorithm for Advanced EGFR-Mutated Non-Small-Cell Lung Cancer

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