Real-World EGFR T790M Testing in Advanced Non-Small-Cell Lung Cancer: A Prospective Observational Study in Japan

Seto, Takashi; Nogami, Naoyuki; Yamamoto, Nobuyuki; Atagi, Shinji; Tashiro, Naoki; Yoshimura, Yoko; Yabuki, Yutaka; Sasaki, Hideo

doi:10.1007/s40487-018-0064-8

Cited by 54 publications

(77 citation statements)

References 36 publications

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“…The detection rates for T790M and TKI‐sensitizing EGFR mutations in plasma were 26.8% (74 of 276 patients) and 62.3% (172 of 276 patients) in our screening of eligible patients for the current study (Supporting Table 1). The rate of plasma positivity for T790M has previously been found to be ~30% in such patients, and this is consistent with our finding. However, the rate of plasma positivity in our study is lower than the rate of tissue positivity in other studies .…”

Section: Discussionsupporting

confidence: 93%

“…Although a repeat biopsy (rebiopsy) has been required to assess the T790M mutation status of a tumor, this procedure can be challenging as a result of the general condition of the patient, the small tumor size, or the inaccessibility of the target lesion, such as a bone or adrenal gland metastasis . As a minimally invasive alternative to tissue biopsy for genetic analysis, liquid biopsy for the genotyping of circulating tumor DNA (ctDNA) has the potential to detect gene alterations in the tumor and may provide a more representative profile of resistance mechanisms for each patient.…”

Section: Introductionmentioning

confidence: 99%

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Plasma screening for the T790M mutation of EGFR and phase 2 study of osimertinib efficacy in plasma T790M–positive non–small cell lung cancer: West Japan Oncology Group 8815L/LPS study

Takahama

Azuma

Shimokawa

et al. 2020

Cancer

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BACKGROUND: Liquid biopsy allows the identification of patients whose tumors harbor specific mutations in a minimally invasive manner. No prospective data have been available for the efficacy of osimertinib in patients with non-small cell lung cancer (NSCLC) who develop resistance to first-or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and who test positive for the TKI resistance-conferring T790M mutation of EGFR by liquid biopsy. Therefore, a phase 2 study was conducted to assess the efficacy and safety of osimertinib in such patients. METHODS: Eligible patients had advanced or recurrent NSCLC with known TKI-sensitizing mutations of EGFR, had documented disease progression after treatment with at least 1 first-or second-generation EGFR TKI, and were positive for the T790M mutation in plasma according to the Cobas EGFR Mutation Test v2 (Roche Diagnostics) or droplet digital polymerase chain reaction analysis. Patients were treated with osimertinib (80 mg/d) until disease progression. The primary endpoint was the overall response rate (ORR) in patients positive for T790M in plasma by the Cobas assay. RESULTS: Between June 2016 and November 2017, 276 patients were screened for their T790M status with a liquid biopsy. Seventy-four patients were positive for T790M in plasma, and 53 of these individuals were enrolled in the study. The ORR for evaluable patients positive for T790M in plasma by the Cobas assay (n = 49) was 55.1% (95% confidence interval [CI], 40.2%-69.3%). The median progression-free survival for all evaluable patients (n = 52) was 8.3 months (95% CI, 6.9-12.6 months). CONCLUSIONS: The results demonstrate the utility of liquid biopsy for the detection of T790M with the Cobas EGFR Mutation Test v2. Plasma genotyping with this assay is informative for treatment selection in clinical practice when tumor sampling is not feasible.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Plasma screening for the T790M mutation of EGFR and phase 2 study of osimertinib efficacy in plasma T790M–positive non–small cell lung cancer: West Japan Oncology Group 8815L/LPS study

Takahama

Azuma

Shimokawa

et al. 2020

Cancer

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“…Seven of these patients (25%) were treated with osimertinib in subsequent therapy lines. In the REMEDY trial conducted in Japan, 61 of 236 patients (25.8%) were positive for T790M mutation, and 56 patients (23.7% in re‐biopsy group) were treated with osimertinib . As 7 of the 28 patients with PD (25.0%) in our study were treated with osimertinib, our clinical practice is equivalent to the REMEDY trial.…”

Section: Discussionmentioning

confidence: 87%

“…In the REMEDY trial conducted in Japan, 61 of 236 patients (25.8%) were positive for T790M mutation, and 56 patients (23.7% in re-biopsy group) were treated with osimertinib. 21 As 7 of the 28 patients with PD (25.0%) in our study were treated with osimertinib, our clinical practice is equivalent to the REM-EDY trial. Asian EGFR-positive NSCLC patients administered sequential afatinib and osimertinib in a real world clinical setting had overall median treatment durations of 27.6 and 46.7 months, respectively.…”

Section: Discussionmentioning

confidence: 99%

Clinical analysis of EGFR‐positive non‐small cell lung cancer patients treated with first‐line afatinib: A Nagano Lung Cancer Research Group

et al. 2019

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Background In the LUX‐Lung 3 and LUX‐Lung 6 trials, afatinib improved overall survival in previously untreated patients with EGFR 19del mutated non‐small cell lung cancer (NSCLC) compared to chemotherapy. The appropriate management of adverse events and dose reduction of afatinib are important for EGFR‐ positive NSCLC patients. We conducted a retrospective and observational study of patients treated with first‐line afatinib for EGFR‐ positive NSCLC in Nagano prefecture, Japan, focusing on efficacy and toxicities. Methods We retrospectively collected the medical records of NSCLC patients initially treated with afatinib between May 2014 and March 2018. Results A total of 62 patients with a median age of 67 years and a median body surface area (BSA) of 1.57 m 2 were included. The overall response rate was 87.7% and median progression‐free survival (PFS) was 15.7 months. The median PFS was similar between standard initial dose (40 mg) and reduced initial doses (30 and 20 mg) (15.7 vs. 14.2 months; P = 0.978). The frequency of dose reduction and the discontinuation rate in the 40 mg daily dose group was higher in patients with BSA < 1.58 m 2 (100%) compared to BSA ≥ 1.58 m 2 (68.2%) ( P = 0.014). The frequency of diarrhea was higher in patients with BSA < 1.58 m 2 (93.5%) compared to BSA ≥ 1.58 m 2 (71.0%) ( P = 0.02). Conclusion In real‐world clinical practice, first‐line afatinib was well managed and was equally as effective as in previous clinical trials of EGFR ‐positive NSCLC. BSA is considered a predictive marker for appropriate afatinib dose reduction.

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“…There is some preliminary evidence to suggest that T790 M detection may be lower in the real-world setting compared with the clinical setting [93], possibly due to poor quality specimens, pre-analytical issues or limited access to liquid biopsies. Further research and development are therefore required to improve the quality and utility of liquid biopsies in clinical practice.…”

Section: T790 M Testing and Failure Ratesmentioning

confidence: 99%

Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC)

Gelatti¹,

2019

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Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 80-85% of cases. Epidermal growth factor receptor (EGFR) mutations are observed in approximately 40% and 20% of patients with NSCLC in Asian and non-Asian populations, respectively. First-generation (gefitinib, erlotinib) and second-generation (afatinib, dacomitinib) EGFR-tyrosine kinase inhibitors (TKIs) have been standard-of-care (SoC) first-line treatment for patients with sensitizing EGFR mutation positive advanced NSCLC following Phase III trials versus platinum-based doublet chemotherapy. However, most patients treated with first-line first-or second-generation EGFR-TKIs develop resistance. Osimertinib, a third-generation, central nervous system active EGFR-TKI which potently and selectively inhibits both EGFR-TKI sensitizing (EGFRm) and the most common EGFR T790 M resistance mutations, has shown superior efficacy versus first-generation EGFR-TKIs (gefitinib / erlotinib). Osimertinib is now a treatment option for patients with advanced NSCLC harboring EGFRm in the first-line setting, and treatment of choice for patients with T790 M positive NSCLC following disease progression on first-line EGFR-TKIs. The second-generation EGFR-TKI dacomitinib has also recently been approved for the first-line treatment of EGFRm positive metastatic NSCLC. There remains a need to determine appropriate sequencing of EGFR-TKIs in this setting, including EGFR-TKIs as monotherapy or in combination with other TKIs / signaling pathway inhibitors. This review considers the evolving role of sequencing treatments to maximize benefits for patients with EGFRm positive advanced NSCLC.

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Real-World EGFR T790M Testing in Advanced Non-Small-Cell Lung Cancer: A Prospective Observational Study in Japan

Cited by 54 publications

References 36 publications

Plasma screening for the T790M mutation of EGFR and phase 2 study of osimertinib efficacy in plasma T790M–positive non–small cell lung cancer: West Japan Oncology Group 8815L/LPS study

Plasma screening for the T790M mutation of EGFR and phase 2 study of osimertinib efficacy in plasma T790M–positive non–small cell lung cancer: West Japan Oncology Group 8815L/LPS study

Clinical analysis of EGFR‐positive non‐small cell lung cancer patients treated with first‐line afatinib: A Nagano Lung Cancer Research Group

Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC)

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