scholarly journals Case report: Management of Progressive Lung Cancer Patients after First-Line EGFR Tyrosine Kinase Inhibitor Therapy

2019 ◽  
Vol 55 (3) ◽  
pp. 239
Author(s):  
Sahrun Sahrun ◽  
Laksmi Wulandari
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Egfr Mutations ◽  
First Line ◽  
T790m Mutation ◽  
Lung Cancer Patients ◽  
First Line Therapy ◽  
Egfr Tki

Various tyrosine kinase inhibitor (TKI) drugs have been widely used as therapy for cancer that has EGFR mutations, or abnormal EGFR activation. However, patients who have a mutation in the gene that activates EGFR only benefit from EGFR-TKI therapy for less than one year, because after that resistance occurs. In the management of patients according to NCCN 2017, patients who experience progress after receiving TKI as the first-line therapy must undergo an examination to identify the presence of T790M mutation. If the T790M mutation is positive, the choice of therapy that needs to be provided is the third generation (Osimertinib). Many recent studies have proved the significance of the effectiveness and response of Osimertinib therapy in lung cancer with EGFR T790M mutation. We reported the management of a pulmonary adenocarcinoma patient with positive EGFR mutation who had received first-line EGFR TKI who had progressive disease and T790M mutation in Dr. Seotomo Hospital. The patient finally received Osimertinib through an Early Access Program with a therapeutic response that improved significantly.

Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer

2020 ◽  
Vol 38 (2) ◽  
pp. 124-136 ◽  
Author(s):  
Vanita Noronha ◽  
Vijay Maruti Patil ◽  
Amit Joshi ◽  
Nandini Menon ◽  
Anuradha Chougule ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Palliative Therapy ◽  
Hazard Ratio ◽  
Phase Iii ◽  
First Line ◽  
A Performance

PURPOSE Standard first-line therapy for EGFR-mutant advanced non–small-cell lung cancer (NSCLC) is an epidermal growth factor receptor (EGFR)–directed oral tyrosine kinase inhibitor. Adding pemetrexed and carboplatin chemotherapy to an oral tyrosine kinase inhibitor may improve outcomes. PATIENTS AND METHODS This was a phase III randomized trial in patients with advanced NSCLC harboring an EGFR-sensitizing mutation and a performance status of 0 to 2 who were planned to receive first-line palliative therapy. Random assignment was 1:1 to gefitinib 250 mg orally per day (Gef) or gefitinib 250 mg orally per day plus pemetrexed 500 mg/m2 and carboplatin area under curve 5 intravenously every 3 weeks for four cycles, followed by maintenance pemetrexed (gefitinib plus chemotherapy [Gef+C]). The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS), response rate, and toxicity. RESULTS Between 2016 and 2018, 350 patients were randomly assigned to Gef (n = 176) and Gef+C (n = 174). Twenty-one percent of patients had a performance status of 2, and 18% of patients had brain metastases. Median follow-up time was 17 months (range, 7 to 30 months). Radiologic response rates were 75% and 63% in the Gef+C and Gef arms, respectively ( P = .01). Estimated median PFS was significantly longer with Gef+C than Gef (16 months [95% CI, 13.5 to 18.5 months] v 8 months [95% CI, 7.0 to 9.0 months], respectively; hazard ratio for disease progression or death, 0.51 [95% CI, 0.39 to 0.66]; P < .001). Estimated median OS was significantly longer with Gef+C than Gef (not reached v 17 months [95% CI, 13.5 to 20.5 months]; hazard ratio for death, 0.45 [95% CI, 0.31 to 0.65]; P < .001). Clinically relevant grade 3 or greater toxicities occurred in 51% and 25% of patients in the Gef+C and Gef arms, respectively ( P < .001). CONCLUSION Adding pemetrexed and carboplatin chemotherapy to gefitinib significantly prolonged PFS and OS but increased toxicity in patients with NSCLC.

NSCLC Patients Harbouring Rare or Complex EGFR Mutations Are More Often Smokers and Might Not Benefit from First-Line Tyrosine Kinase Inhibitor Therapy

Respiration ◽  
2017 ◽  
Vol 95 (3) ◽  
pp. 169-176 ◽  
Author(s):  
Diego Kauffmann-Guerrero ◽  
Rudolf Maria Huber ◽  
Simone Reu ◽  
Amanda Tufman ◽  
Pontus Mertsch ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Inhibitor Therapy ◽  
Egfr Mutations ◽  
First Line ◽  
Tyrosine Kinase Inhibitor Therapy ◽  
Nsclc Patients

ctDNA levels before treatment predict survival in non-small cell lung cancer patients treated with a tyrosine kinase inhibitor.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9542-9542
Author(s):  
Mariano Provencio-Pulla ◽  
Roberto Serna ◽  
Fernando Franco ◽  
Alfredo Sanchez ◽  
Carlos García Girón ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Treatment Initiation ◽  
Kinase Inhibitor ◽  
Cox Proportional Hazards ◽  
Egfr Mutations ◽  
Plasma Samples ◽  
First Line ◽  
Cross Sectional ◽  
Nsclc Patients

9542 Background: Currently there is an intense debate concerning therapeutic strategies in EGFR positive NSCLC patients with advance disease. Osimertinib is superior to standard EGFR Tyrosine Kinase Inhibitors (TKIs) as first line treatment. However, it is yet unclear whether this option is superior to sequential treatment of a 1st or 2nd generation TKI followed by osimertinib. In order to clarify this issue it is important to identify which patients are at high risk of progression disease. Methods: This is a prospective, multicentre, cross-sectional study promoted by Spanish Lung Cancer Group. 698 plasma samples from 196 advanced NSCLC patients with tumors harboring an EGFR activating mutation and treated with a first line TKI (afatinib, gefitinib, erlotinib or osimertinib) were analyzed. Plasma samples were prospectively collected before treatment (T0), after 3 months of treatment (T3), after 6 months of treatment (T6) and at first disease progression. EGFR mutations were analyzed by dPCR. Multivariate Cox proportional hazards analysis was used to determine the significance of ctDNA in the prediction of prognosis. Results: The median follow up was 19.8 months. At baseline patients with plasma EGFR sensitizing mutations at allele frequency (AF) ≥ 10% had worse OS and PFS than patients in which the opposite occurred (HR = 1.86; 95 %CI: 1.09-3.17, and HR = 1.65; 95 %CI: 1.07-2.58, respectively). Noteworthy, median OS and PFS time were 18.6 and 8.8 months respectively, in patients with plasma AF≥10% before treatment initiation compared to 37.9 and 12.4 months for patients with plasma AF < 10%. Similar results were obtained when a cutoff of AF≥ 5% was used (HR = 1.73; 95%CI: 1.02-2.94 for OS, and HR = 1.72; 95%CI: 1.13-2.61 for PFS). Patients who remained ctDNA-positive after 3 months of treatment exhibited also poorer outcomes (HR = 3.24; 95%CI: 1.77-5.94 for OS, and HR = 3.1; 95%CI: 1.91-5.03 for PFS). In the same way, detectable levels of ctDNA after 6 months of treatment predicted shorter OS and PFS (HR = 3.3; 95%CI: 1.53-7.13 and HR = 2.62; 95%CI: 1.62-4.25, respectively). Conclusions: ctDNA levels significantly predict survival. Moreover, ctDNA levels before treatment initiation can be useful to assess patient’s progression risk which is not possible to assess otherwise facilitating treatment decision making.

scholarly journals Genetic diagnostic features after failure of initial treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors among non-small-cell lung cancer patients harboring EGFR mutations

2020 ◽  
Author(s):  
Yuichiro Takeda ◽  
Go Naka ◽  
Yoh Yamaguchi ◽  
Masao Hashimoto ◽  
Manabu Suzuki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
First Line ◽  
Lung Cancer Patients ◽  
Epidermal Growth ◽  
Egfr Tki ◽  
Egfr Tkis

Abstract Background: Osimertinib, a third - generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), can be used as a second-line treatment for lung cancer patients harboring the T790M substitution. Although osimertinib is more effective than the first-generation EGFR-TKIs used for first-line treatment, its efficacy with respect to long-term patient survival remains unclear even upon the administration of a complete sequence of EGFR-TKI therapy, and limited information is available regarding genetic diagnostic approaches after EGFR-TKI naïve treatment. This study investigated the characteristics of EGFR-mutated lung cancer patients harboring the T790M substitution resistance to EGFR-TKIs and the advantages of rebiopsy and liquid biopsy for these patients. Methods: The medical records of patients screened for EGFR mutations were reviewed. Upon failure of naïve treatment with EGFR-TKIs, except for osimertinib, single plexus cobas version 2 was repeatedly used to detect the T790M substitution in EGFR via tissue or liquid biopsy. Results: From April 2016 through May 2019, 113 patients were determined to harbor EGFR mutations. Sixty patients were treated with EGFR-TKIs, among which 46 underwent tissue or liquid biopsy. Twenty-nine of these 46 (63%) patients harbored the T790M substitution. In total, 141 rebiopsies were performed. The T790M substitution was detected in 24 of 43 tissue and 11 of 98 liquid biopsies. If patients displayed an EGFR exon 19 deletion, had new lesions, and were administered gefitinib as first-line therapy, patients harboring an EGFR mutation were suspected of harboring the T790M substitution. Furthermore, the T790M substitution was detected through rebiopsy in patients with co-existing original mutations, brain metastases, tumor enlargement by ≥ 12 mm, or metastases at minor sites. Conclusion: Repeated biopsy can help maximize the detection rate of the T790M substitution. Furthermore, the advantages of repeated tissue or liquid biopsy should be considered among patients with positive T790M factors , and these biopsies can be repeated numerous times .

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