Selectivity profile of afatinib for EGFR-mutated non-small-cell lung cancer

8501 Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor is a standard of care for EGFR mutation-positive, untreated metastatic non-small cell lung cancer (NSCLC). However, the efficacy and safety of adjuvant gefitinib for patients with completely resected lung cancer harboring EGFR mutation over cisplatin-based adjuvant chemotherapy were not known in 2011 when this study was initiated. Methods: From September 2011 to December 2015, we randomly assigned 234 patients with completely resected, EGFR mutation-positive (exon 19 deletion or L858R), stage II–III NSCLC to receive either gefitinib (250 mg, once daily) for 24 months or cisplatin (80 mg/m2 on day 1) plus vinorelbine (25 mg/m2 on days 1 and 8) (cis/vin) every 3 weeks for four cycles. The primary endpoint was disease-free survival (DFS) according to a central review in the intent-to-treat (ITT) population. Results: Two patients in the gefitinib arm withdrew consent and were excluded from the ITT population. No treatment-related deaths were seen in the gefitinib arm, but three treatment-related deaths were reported in the cis/vin arm. Median duration of follow-up was 71 months. Median DFS was numerically longer in the gefitinib arm (36 months) than in the cis/vin arm (25.2 months). However, Kaplan-Meier curves began to overlap around 5 years after surgery, and no significant difference in DFS was seen, with a hazard ratio (HR) of 0.92 (95% confidence interval (CI), 0.67–1.28; P = 0.63). Overall survival was also not significantly different (median not reached in either arm). Five-year survival rates for gefitinib and cis/vin arms were 78.0% and 74.6%, respectively, with an HR for death of 1.03; 95%CI, 0.65–1.65; P = 0.89. Exploratory subset analysis revealed that patients ³70 years old in the gefitinib arm (n = 19/27 with G to cis/vin) survived longer than those in the cis/vin arm (HR 0.31; 95%CI, 0.10–0.98; P = 0.046). Conclusions: Adjuvant gefitinib appeared to prevent early relapse, but did not significantly prolong DFS or OS in patients with completely resected stage II–III, EGFR-mutated NSCLC. The apparent non-inferiority of DFS/OS may justify the use of adjuvant gefitinib in selected subset of patients, especially those deemed unsuitable for cis/vin adjuvant therapy. Clinical trial information: UMIN000006252.

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Prevalence of EGFR mutations in non-small cell lung cancer (NSCLC) smoker patients.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e21015 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e21015-e21015 ◽

Cited By ~ 1

Author(s):

Yann Izarzugaza ◽

Manuel Domine ◽

Federico Rojo ◽

Victoria Casado ◽

Ana Leon ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Egfr Mutation ◽

Small Cell ◽

Egfr Mutations ◽

Small Cell Lung ◽

Exon 20 ◽

Egfr Mutated ◽

Exon 19

e21015 Background: Mutations in the Epidermal Growth Factor Receptor (EGFR) predict a better response to tyrosine kinase inhibitors compared to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Previous studies in caucasian population have reported a frequency of EGFR mutation of 10-15%. The aim of this study is to analyze the prevalence of EGFR mutations in caucasian smoker patients with NSCLC. Methods: Prospective mutation testing in NSCLC patients included in our institution since October 2010 to January 2012 was performed on DNA obtained from available tumor tissue and cytologic samples, using ARMS-scorpion TheraScreen EGFR 29 Mutation Test Kit (Qiagen). Results: From 218 consecutive NSCLC diagnoses, 18 (8.25%) patients showed EGFR mutations: 6 (33.3%) exon 19 deletions, 9 (50%) exon 21 mutations (7 cases L858R and 2 cases L861Q) and 3 (16.6%) exon 20 insertions. In the EGFR-mutated patients, 13 (72.25%) were never-smoker and 5 (27.7%) were smoker (3 current-smoker and 2 former-smoker). The EGFR-mutated smoker population showed the following characteristics: 3 female, 2 male; 4 adenocarcinoma, one squamous cell carcinoma; 3 stage IV, 2 stage IA at diagnosis; 1 (20%) case EGFR deletion exon 19, 1 (20%) case insertion exon 20 and 3 patients (60%) mutation exon 21 (2, L858R and 1, L861Q). Conclusions: The EGFR mutation rate in NSCLC smoking patients in our referral area is superior (27.7%) than previously reported, reinforcing the importance of including EGFR mutation testing in NSCLC smoking population for the correct management of these patients.

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EGFR mutation tracking predicts survival in advanced EGFR-mutated non-small cell lung cancer patients treated with osimertinib

Translational Lung Cancer Research ◽

10.21037/tlcr.2020.03.02 ◽

2020 ◽

Vol 9 (2) ◽

pp. 239-245 ◽

Cited By ~ 1

Author(s):

Anna Buder ◽

Maximilian J. Hochmair ◽

Ulrike Setinek ◽

Robert Pirker ◽

Martin Filipits

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cancer Patients ◽

Cell Lung Cancer ◽

Egfr Mutation ◽

Small Cell ◽

Small Cell Lung ◽

Lung Cancer Patients ◽

Egfr Mutated

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Plasma Predictive Features in Treating EGFR-Mutated Non-Small Cell Lung Cancer

Cancers ◽

10.3390/cancers12113179 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3179

Author(s):

Christi M. J. Steendam ◽

G. D. Marijn Veerman ◽

Melinda A. Pruis ◽

Peggy Atmodimedjo ◽

Marthe S. Paats ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Kinase Inhibitors ◽

Egfr Mutation ◽

Plasma Concentrations ◽

Small Cell ◽

Small Cell Lung ◽

The Impact ◽

Egfr Mutated

Although epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the preferred treatment for patients with EGFR-mutated non-small cell lung cancer (NSCLC), not all patients benefit. We therefore explored the impact of the presence of mutations found in cell-free DNA (cfDNA) and TKI plasma concentrations during treatment on progression-free survival (PFS). In the prospective START-TKI study blood samples from 41 patients with EGFR-mutated NSCLC treated with EGFR-TKIs were available. Next generation sequencing (NGS) on cfDNA was performed, and plasma TKI concentrations were measured. Patients without complete plasma conversion of EGFR mutation at week 6 had a significantly shorter PFS (5.5 vs. 17.0 months, p = 0.002) and OS (14.0 vs. 25.5 months, p = 0.003) compared to patients with plasma conversion. In thirteen (second line) osimertinib-treated patients with a (plasma or tissue) concomitant TP53 mutation at baseline, PFS was significantly shorter compared to six wild-type cases; 8.8 vs. 18.8 months, p = 0.017. Erlotinib Cmean decrease of ≥10% in the second tertile of treatment was also associated with a significantly shorter PFS; 8.9 vs. 23.6 months, p = 0.037. We obtained evidence that absence of plasma loss of the primary EGFR mutation, isolated plasma p.T790M loss after six weeks, baseline concomitant TP53 mutations, and erlotinib Cmean decrease during treatment are probably related to worse outcome.

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Effectiveness of osimertinib plus chemotherapy and avastin for untreated EGFR-mutated advanced non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21178 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21178-e21178

Author(s):

Fang Wang ◽

Hui Liu ◽

Zhen Zeng ◽

Shasha Wang ◽

Haifeng Qin

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Egfr Mutation ◽

Advanced Nsclc ◽

Objective Response ◽

Small Cell ◽

Small Cell Lung ◽

Nsclc Patients ◽

Egfr Mutated

e21178 Background: Osimertinib is recommended as a novel first-line standard treatment for advanced Non-Small-Cell Lung Cancer (NSCLC) patients with EGFR mutation. However, there are also patients with concurrent mutation or/and metastases have limited benefits. According to the current remission rate, regression depth and PFS data, the main mechanism of the benefit of combined anti-angiogenesis or chemotherapy is to reduce tumor load and heterogeneous reserve to a greater extent, so as to extend the remission time, that is, to delay the occurrence of drug resistance to extend PFS. This prospective study aims to investigate the efficacy and safety of Osimertinib plus chemotherapy and Avastin for Untreated EGFR-Mutated advanced NSCLC. Methods: The study enrolled 22 patients diagnosed with untreated advanced NSCLC and tested with EGFR mutation, who received osimertinib ( 80mg QD) plus pemetrexed (500mg/m2), cisplatin (75mg/m2) and bevacizumab (7.5mg/kg) for 6 cycles, then maintained with osimertinib/pemetrexed/bevacizumab. The primary endpoint was progression free survival (PFS). The secondary endpoint was objective response rate (ORR). Treatment was continued until disease progression and the tumor response was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. The toxicity was determined according to CTCAE 4.0. Results: From February, 2018 to July, 2020, 22 patients enrolled. All the patients were evaluated and showed partial response(PR) when make efficacy evaluation at the first time. The target lesions reduction were shown. The average reduction is 48%, ranged from 32% of Pt12 to 71% of Pt11. Up to January, 2021, all the patients are still under the treatment. Especially for Pt7 who has already benefited from the treatment protocol by 35months. The toxicities associated with this protocols were manageable. Only 1 patient was 3/4-grade Anemia, 1 patient was 3/4-grade Diarrhea and 3 patients was 3/4-grade Lymphopenia. Conclusions: Osimertinib in combination with chemotherapy and Bevacizumab. exhibits superior activity and generally manageable toxicities for the naive advanced NSCLC patients with EGFR mutant, especially for the patients with concurrent mutation or/and metastases. It may provide a new and effective therapy strategy for them, but large sample and additional clinical trials are also needed.

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