Background: In most cases, T790M EGFR-positive NSCLC patients receiving osimertinib developed "non-drugable" progression, as the patients with common EGFR-sensitizing mutations were treated with first-line osimertinib. In both settings, chemotherapy represents the standard treatment and local ablative treatments (LATs) are potential useful options in the case of oligo-progression.
Methods: We conducted a study on "post-progression" (pp) outcomes of T790M EGFR-positive NSCLC patients treated with osimertinib, according to the therapeutic strategy applied: osimertinib beyond progression (± LATs), "switched therapies" or best supportive care only (BSC).
Results: 144 consecutive patients were evaluated: 53 (36.8%) did not received post-progression treatments (BSC), while 91 (63.2%) patients received at least 1 subsequent treatment; 50 patients (54.9%) received osimertinib beyond disease progression [19 (20.9%) of them with adjunctive LATs] and 41 (45.1%) a switched therapy. Median ppPFS (progression-free survival) and median ppOS (overall survival) of patients who received osimertinib beyond progression vs. switched therapies were 6.4 months vs. 4.7 months, respectively [HR 0.57 (95% CI 0.35-0.92), p = 0.0239] and 11.3 months vs 7.8 months, respectively [HR 0.57 (95% CI 0.33-0.98), p = 0.0446]. Among patients who received osimertinib beyond progression with and without LATs median ppPFS was 6.4 months and 5.7 months, respectively [HR 0.90 (95% CI 0.68-1.18), p = 0.4560], while median ppOS was 20.2 months and 9.9 months, respectively [HR 0.73 (95% CI 0.52-1.03), p = 0.0748]. At the univariate analysis, the only factor significantly related to the ppPFS was the therapeutic strategy in favor of osimertinib beyond progression (± LATs). Moreover, the only variable which was significantly related to ppOS at the multivariate analysis was osimertinib beyond progression (± LATs).
Conclusion: Our study confirmed that in clinical practice, in case of "non-druggable" disease progression, maintaining osimertinib beyond progression (with adjunctive LATs) is an effective option.
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http://dx.doi.org/10.1007/s12094-019-02193-w | DOI Listing |
J Cancer Res Ther
December 2024
Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Lung Cancer Institute, Shandong, China.
Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), has revolutionized one of the standard most efficient treatments for EGFR mutation-positive non-small cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR-TKI, is currently one of most efficient treatments in clinical practice. However, it has a potentially fatal side effect: interstitial lung disease (ILD).
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January 2025
Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) effectively treat EGFR-mutant lung adenocarcinoma, demonstrating initial efficacy but eventually leading to acquired resistance. Small cell transformation is a rare resistance mechanism to EGFR-TKIs in lung adenocarcinoma, which can complicate clinical diagnosis and treatment. We present a patient with lung adenocarcinoma who underwent a prior pneumonectomy and adjuvant chemotherapy and was treated with osimertinib after the recurrence of lung cancer.
View Article and Find Full Text PDFInvest New Drugs
January 2025
Center for Biomedical Sciences, Wakayama Medical University, Wakayama, Japan.
The impact of clinical stage on the effectiveness of osimertinib for epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) remains unexamined. We investigated osimertinib therapeutic efficacy variation between stage IVA or lower and stage IVB EGFR mutation-positive lung cancers, focusing on differences in pretreatment co-occurring genetic alterations in circulating tumor DNA. This was a secondary analysis of the ELUCIDATOR study, a multicenter prospective observational study in Japan that assessed the mechanisms underlying resistance to osimertinib as a first-line treatment for advanced NSCLC with EGFR mutations.
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January 2025
Department of Respiratory and Critical Care Medicine, The Second People's Hospital of Jingdezhen, Jingdezhen, China.
The prevailing belief is that third-generation tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) (TGET) outperform first-generation EGFR-TKIs (FGET) in managing advanced-stage EGFR-mutated non-small cell lung cancer (NSCLC). However, this standpoint lacks substantiation in evidence-based medicine. Therefore, this meta-analysis was conducted to compare the efficacy and adverse effects (AEs) of these two categories.
View Article and Find Full Text PDFMol Oncol
January 2025
Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, Italy.
Extracellular vesicle (EV) monitoring can complement clinical assessment of cancer response. In this study, patients with advanced non-small cell lung cancer (NSCLC) undergoing osimertinib, alectinib, pembrolizumab or platinum-based chemotherapy ± pembrolizumab were enrolled. EVs were characterized using Bradford assay to quantify the circulating cell-free EV protein content (cfEV), and dynamic light scattering to assess Rayleigh ratio excess at 90°, z-averaged hydrodynamic diameter and polydispersity index.
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