Real-life efficacy of osimertinib in pretreated patients with advanced non-small cell lung cancer harboring EGFR T790M mutation

Auliac, Jean Bernard; Pérol, Maurice; Planchard, David; Monnet, I.; Wislez, Marie; Doubre, H.; Guisier, Florian; Pichon, Éric; Greillier, L.; Mastroïanni, B.; Decroisette, C.; Schött, Roland; Moulec, Sylvestre Le; Arrondeau, Jennifer; Cortot, A.; Gérinière, L.; Renault, Aldo; Daniel, Catherine; Falchero, L.; Chouaïd, C.

doi:10.1016/j.lungcan.2018.11.037

Cited by 37 publications

(47 citation statements)

References 22 publications

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“…Given all of the above, we believe that it is important to report real-world data from patients treated with osimertinib in any line. Our results with 155 patients are similar to those of real-world studies in China with 77 patients [21], Germany with 51 [15], or France with 205 patients [22] and demonstrate that realworld data closely agrees with that obtained in pivotal clinical trials, even without hyperselection of patients.…”

Section: Resultssupporting

confidence: 86%

Osimertinib in Advanced EGFR-T790M Mutation-positive Non-small Cell Lung Cancer Patients Treated Within the Special Use Medication Program in Spain. OSIREX-spanish Lung Cancer Group

Provencio

Terrasa

Garrido

et al. 2020

Preprint

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Background: AURA study reported 61% objective response rate and progression-free survival of 9.6 months with osimertinib in patients with EGFR/T790M+ non-small cell lung cancer. Due to lack of real-world data, we proposed this study to describe the experience with osimertinib in Spain.Methods: Post-authorization, non-interventional Special Use Medication Program, multicenter, retrospective study in advanced EGFR/T790M+ non-small cell lung cancer. 155 patients were enrolled (August 2016-December 2018) from 30 sites. Primary objective: progression-free survival. Secondary objectives: toxicity profile, objective response rate, and use of health service resources.Results: 70% women, median age 66. 63.9% were non-smokers and 99% had adenocarcinoma. Most had received at least one prior treatment (97%), 91.7% had received previous EGFR-tyrosine kinase inhibitors and 2.8% osimertinib as first-line treatment. At data cutoff, median follow-up was 11.8 months. 155 patients were evaluable for response, 1.3% complete response, 40.7% partial response, 31% stable disease and 11.6% progressive disease. Objective response rate was 42%. Median progression-free survival was 9.4 months. 49% reported an adverse event, the majority of which (78%) were grade 1 or 2. The resource cost study indicates early use is warranted. Conclusion: This study to assess the real-world clinical impact of osimertinib showed high drug activity in pretreated advanced EGFR/T790M+ non-small cell lung cancer, with manageable adverse events.Clinical trial registration number: NCT03790397

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Section: Resultssupporting

confidence: 86%

Osimertinib in Advanced EGFR-T790M Mutation-positive Non-small Cell Lung Cancer Patients Treated Within the Special Use Medication Program in Spain. OSIREX-spanish Lung Cancer Group

Provencio

Terrasa

Garrido

et al. 2020

Preprint

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“…In contrast, either of the combinations of L858R with C797S, C797G, L718Q, or L718V mutations conferred resistance to osimertinib, indicating that the type of co-existing sensitizing EGFR -mutation may affect the resistance to first- or second-line osimertinib too [275]. Similar results have recently been seen in T790M-positive NSCLC patients receiving osimertinib as second- or third-line, in that those with co-existing EGFR exon 19del displayed longer PFS and OS than patients harboring L858R co-mutation [23]. Consistent with the results by Niederst et al [272], erlotinib showed the greatest activity for C797S-mediated resistance, whereas the 2G TKIs afatinib and dacomitinib were effective for other osimertinib-resistant mutations [275].…”

Section: Further Considerations Regarding the 3g Egfr-tki Osimertinibmentioning

confidence: 69%

“…In terms of the overall survival (OS) rate, more mature clinical trial data for osimertinib second-line (129 patients) or third- or later-line (282 patients) in pretreated T790M-mutant patients were recently reported, showing a median OS of 26.8 months and a 12-month, 24-month, and 36-month survival rate of 80%, 55%, and 37%, respectively, further supporting the choice of this drug in these patients [22]. Outside clinical trials, a recent retrospective multicentric study of T790M-positive patients confirmed the efficacy of second-/third-line osimertinib in a real-world setting, both in patients with and without cerebral metastases [23].…”

Section: Introductionmentioning

confidence: 97%

Intrinsic Resistance to EGFR-Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer: Differences and Similarities with Acquired Resistance

Santoni-Rugiu

Melchior

Urbanska

et al. 2019

Cancers

127

126

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Activating mutations in the epidermal growth factor receptor gene occur as early cancer-driving clonal events in a subset of patients with non-small cell lung cancer (NSCLC) and result in increased sensitivity to EGFR-tyrosine-kinase-inhibitors (EGFR-TKIs). Despite very frequent and often prolonged clinical response to EGFR-TKIs, virtually all advanced EGFR-mutated (EGFRM+) NSCLCs inevitably acquire resistance mechanisms and progress at some point during treatment. Additionally, 20–30% of patients do not respond or respond for a very short time (<3 months) because of intrinsic resistance. While several mechanisms of acquired EGFR-TKI-resistance have been determined by analyzing tumor specimens obtained at disease progression, the factors causing intrinsic TKI-resistance are less understood. However, recent comprehensive molecular-pathological profiling of advanced EGFRM+ NSCLC at baseline has illustrated the co-existence of multiple genetic, phenotypic, and functional mechanisms that may contribute to tumor progression and cause intrinsic TKI-resistance. Several of these mechanisms have been further corroborated by preclinical experiments. Intrinsic resistance can be caused by mechanisms inherent in EGFR or by EGFR-independent processes, including genetic, phenotypic or functional tumor changes. This comprehensive review describes the identified mechanisms connected with intrinsic EGFR-TKI-resistance and differences and similarities with acquired resistance and among clinically implemented EGFR-TKIs of different generations. Additionally, the review highlights the need for extensive pre-treatment molecular profiling of advanced NSCLC for identifying inherently TKI-resistant cases and designing potential combinatorial targeted strategies to treat them.

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“…The current study also provided some evidence that the type of activating mutation impacted on OS, although the difference was not statistically significant. In another analysis based on a larger group of osimertinib-treated patients in clinical practice, median OS was significantly longer in subjects with exon 19 deletions than in patients with exon 21 mutations (23.1 vs 15.3 months; p = 0.03) [11].…”

Section: Discussionmentioning

confidence: 93%

Effectiveness of Osimertinib in Patients with Lung Adenocarcinoma in Clinical Practice—The Expanded Drug Access Program in Poland

Knetki-Wróblewska

Kowalski

Czyżewicz

et al. 2020

Advances in Respiratory Medicine

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Introduction: Osimertinib is a third-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated efficacy in the treatment of EGFR-mutant non-small-cell lung cancer (NSCLC) in prospective clinical trials. Material and methods: This retrospective analysis evaluated the outcomes of 32 pretreated patients with EGFR T790M mutation who received osimertinib in clinical practice at seven centers in Poland within the Expanded Drug Access Program. Osimertinib was used in the second line in 59% of patients and in later lines in 41%. Results: Objective response was attained in 16 patients (50%), and 12 subjects (38%) had stable disease. Median progression-free survival was 11.3 months in the overall population, 12.6 months in patients with EGFR exon 19 mutation and 7.5 months in patients with EGFR exon 21 mutation (p = 0.045). Median overall survival (OS) was 18.3 months. Overall, 58.4% and 45.6% of patients remained in follow-up after 12 and 24 months, respectively. Median OS appeared longer for patients without cerebral metastases than for those with cerebral metastases (27.4 vs 9.4 months, respectively; p = 0.078), and for patients with the Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 than those with ECOG PS 2 (27.4 vs 11.8 months, respectively; p = 0.189), although neither result reached statistical significance. Median OS of patients with partial response, stable disease and progressive disease was 27.4, 12.7 and 4.5 months, respectively (p < 0.001). Age, comorbidities, line of treatment with osimertinib, and type of activating EGFR mutation did not impact on OS. Adverse events of any grade or grade 3/4 were reported in 38% and 9% of patients, respectively. One person discontinued due to interstitial pneumonia. Conclusion: These results confirm the value of osimertinib in patients with previously treated EGFR T790M-mutant NSCLC. Clinical benefit was evident in patients with cerebral metastases and moderate performance status.

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Real-life efficacy of osimertinib in pretreated patients with advanced non-small cell lung cancer harboring EGFR T790M mutation

Cited by 37 publications

References 22 publications

Osimertinib in Advanced EGFR-T790M Mutation-positive Non-small Cell Lung Cancer Patients Treated Within the Special Use Medication Program in Spain. OSIREX-spanish Lung Cancer Group

Osimertinib in Advanced EGFR-T790M Mutation-positive Non-small Cell Lung Cancer Patients Treated Within the Special Use Medication Program in Spain. OSIREX-spanish Lung Cancer Group

Intrinsic Resistance to EGFR-Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer: Differences and Similarities with Acquired Resistance

Effectiveness of Osimertinib in Patients with Lung Adenocarcinoma in Clinical Practice—The Expanded Drug Access Program in Poland

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Real-life efficacy of osimertinib in pretreated patients with advanced non-small cell lung cancer harboring EGFR T790M mutation

Cited by 37 publications

References 22 publications

Osimertinib in Advanced EGFR-T790M&nbsp;Mutation-positive Non-small Cell Lung Cancer Patients Treated Within the Special Use Medication Program in Spain. OSIREX-spanish Lung Cancer Group

Osimertinib in Advanced EGFR-T790M&nbsp;Mutation-positive Non-small Cell Lung Cancer Patients Treated Within the Special Use Medication Program in Spain. OSIREX-spanish Lung Cancer Group

Intrinsic Resistance to EGFR-Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer: Differences and Similarities with Acquired Resistance

Effectiveness of Osimertinib in Patients with Lung Adenocarcinoma in Clinical Practice—The Expanded Drug Access Program in Poland

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Osimertinib in Advanced EGFR-T790M Mutation-positive Non-small Cell Lung Cancer Patients Treated Within the Special Use Medication Program in Spain. OSIREX-spanish Lung Cancer Group

Osimertinib in Advanced EGFR-T790M Mutation-positive Non-small Cell Lung Cancer Patients Treated Within the Special Use Medication Program in Spain. OSIREX-spanish Lung Cancer Group