Treating EGFR-Mutant Advanced Lung Cancer With Acquired Resistance

2021 ◽  
Keyword(s):  
Lung Cancer ◽  
Acquired Resistance ◽  
Advanced Lung Cancer ◽  
Egfr Mutant

Delay of chemotherapy through use of post-progression erlotinib in patients with EGFR-mutant lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7547-7547 ◽  
Author(s):  
Geoffrey R. Oxnard ◽  
Peter Lo ◽  
David Michael Jackman ◽  
Mohit Butaney ◽  
Stephanie Heon ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Lung Cancer ◽  
Systemic Therapy ◽  
Acquired Resistance ◽  
Local Treatment ◽  
Treatment Modalities ◽  
Advanced Lung Cancer ◽  
Egfr Mutant ◽  
Exon 19

7547 Background: 1st-line tyrosine kinase inhibitor (TKI) therapy for patients (pts) with EGFR-mutant lung cancer prolongs progression free survival (PFS) and improves quality of life. When pts develop acquired resistance to TKI, chemotherapy is the only approved systemic treatment. Anecdotal evidence suggests that change of therapy can be delayed in some pts through continued TKI beyond progression (PD), but the effectiveness of this approach has not been quantified. Methods: Through an IRB-approved mechanism, pts with advanced lung cancer and EGFR sensitizing mutations treated on 3 prospective trials of 1st-line erlotinib were identified. Only pts with RECIST PD while on erlotinib were studied. Time from PD until use of an alternate systemic therapy (or death) and characteristics at PD (development of new extra-thoracic metastases or cancer-related symptoms) were assessed. Results: 42 eligible pts were identified with the following characteristics: median age 70, 86% female, 93% non-Asian, 50% never-smokers, 83% adenocarcinoma, 100% EGFR-mutant (55% exon 19, 36% exon 21, 9% exon 18). Median PFS on erlotinib was 13 months. After PD, alternate systemic therapy was delayed >3 months in 19 pts (45%; 95%CI: 31%-60%), through a combination of post-PD erlotinib (16 pts), radiation (6 pts), and/or surgery (3 pts), or on observation alone (2 pts). These 19 pts commonly had exon 19 deletions and were more likely to have no cancer-related symptoms at PD (Table), and had a median post-PD survival of 29 months. Alternate systemic therapy was delayed >12 months in 8 pts (19%). Conclusions: In a subset of pts with EGFR-mutant lung cancer and acquired resistance to TKI, chemotherapy can be delayed with the aid of post-PD TKI and local treatment modalities. This indolent PD is likely due to ongoing tumor EGFR dependence. In pts who are tolerating TKI and have asymptomatic progression, we recommend this palliative treatment strategy as an option for delaying chemotherapy and maximizing quality of life. [Table: see text]

scholarly journals Cisplatin Synergistically Enhances Antitumor Potency of Conditionally Replicating Adenovirus via p53 Dependent or Independent Pathways in Human Lung Carcinoma

2019 ◽  
Vol 20 (5) ◽  
pp. 1125 ◽  
Author(s):  
Sakhawat Ali ◽  
Muhammad Tahir ◽  
Aamir Khan ◽  
Xue Chen ◽  
Ma Ling ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Combined Treatment ◽  
Acquired Resistance ◽  
Chemotherapy Resistance ◽  
Chemotherapeutic Agents ◽  
Lung Cancer Cells ◽  
Advanced Lung Cancer ◽  
Mesenchymal Transition ◽  
Conditionally Replicating Adenovirus

Cisplatin is ranked as one of the most powerful and commonly prescribed anti-tumor chemotherapeutic agents which improve survival in many solid tumors including non-small cell lung cancer. However, the treatment of advanced lung cancer is restricted due to chemotherapy resistance. Here, we developed and investigated survivin promoter regulating conditionally replicating adenovirus (CRAd) for its anti-tumor potential alone or in combination with cisplatin in two lung cancer cells, H23, H2126, and their resistant cells, H23/CPR, H2126/CPR. To measure the expression of genes which regulate resistance, adenoviral transduction, metastasis, and apoptosis in cancer cells, RT-PCR and Western blotting were performed. The anti-tumor efficacy of the treatments was evaluated through flow cytometry, MTT and transwell assays. This study demonstrated that co-treatment with cisplatin and CRAd exerts synergistic anti-tumor effects on chemotherapy sensitive lung cancer cells and monotherapy of CRAd could be a practical approach to deal with chemotherapy resistance. Combined treatment induced stronger apoptosis by suppressing the anti-apoptotic molecule Bcl-2, and reversed epithelial to mesenchymal transition. In conclusion, cisplatin synergistically increased the tumor-killing of CRAd by (1) increasing CRAd transduction via enhanced CAR expression and (2) increasing p53 dependent or independent apoptosis of lung cancer cell lines. Also, CRAd alone proved to be a very efficient anti-tumor agent in cancer cells resistant to cisplatin owing to upregulated CAR levels. In an exciting outcome, we have revealed novel therapeutic opportunities to exploit intrinsic and acquired resistance to enhance the therapeutic index of anti-tumor treatment in lung cancer.

scholarly journals Acquired Resistance to EGFR TKIs Mediated by TGFβ1/Integrin β3 Signaling in EGFR-Mutant Lung Cancer

2019 ◽  
Vol 18 (12) ◽  
pp. 2357-2367 ◽  
Author(s):  
Caiyun Wang ◽  
Tao Wang ◽  
Dacheng Lv ◽  
Ling Li ◽  
Jinnan Yue ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Acquired Resistance ◽  
Integrin Β3 ◽  
Egfr Mutant ◽  
Egfr Tkis

Acquired Resistance to Afatinib in EGFR-Mutant Lung Cancer

2014 ◽  
Vol 90 (5) ◽  
pp. S43-S44 ◽  
Author(s):  
L.V. Sequist ◽  
D.E. Gerber ◽  
P. Fidias ◽  
A.T. Shaw ◽  
J.S. Temel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Acquired Resistance ◽  
Egfr Mutant

Clinical outcomes of NSCLC patients with acquired RET rearrangement after resistance to osimertinib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20626-e20626
Author(s):  
Chang Lu ◽  
Jia-Tao Cheng ◽  
Jin Kang ◽  
Yi-Hui Yao ◽  
Xiang-Meng Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Outcomes ◽  
Acquired Resistance ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Line Treatment ◽  
Significant Difference ◽  
Ret Rearrangement ◽  
Egfr Mutant

e20626 Background: Resistance mechanisms to osimertinib have raised growing concerns, but those with acquired RET rearrangement is poorly characterized. Methods: We retrospectively identified advanced, EGFR-mutant NSCLC (non-small-cell lung cancer) patients treated with osimertinib between April 9th, 2015 and November 1st, 2018 at our institute. Clinicopathologic features and clinical outcomes were analyzed. Subsequent genetic profiling was performed at the time of progression by next-generation sequencing (NGS). Overall survival (OS) since 1st line treatment was calculated from first-line treatment start to death or last follow up, and OS post-progression was calculated from osimertinib progression. Median follow-up time was 43.4 months. Results: In the 192 patients treated with osimertinib, 57 had follow-up NGS information after progression, and six harboured acquired RET rearrangement (11%, 6/57). For patients with RET rearrangements when progressed on osimertinib, OS since 1st line treatment (22.9m vs 59.5m, P = 0.021) and OS post-progression (2.1m vs 10.0m, P = 0.031) were significantly shorter compared with non- RET-rearranged cases, whereas no significant difference was found in demographics at the initial lung cancer diagnosis or progression-free survival (PFS) of osimertinib (12.1m vs 5.8m, P = 0.34). Among these six patients, one received best supportive care, two continued to use drugs targeting EGFR but deteriorating soon, three patients tried osimertinib combined with cabozantinib with one benefit from this combination approach. Conclusions: RET rearrangements could exist in EGFR-mutant NSCLC with acquired resistance to osimertinib and linked to inferior survival. Study on the molecular evolution and heterogeneity during treatment course are warranted for further therapeutic strategies. [Table: see text]

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