Association Between EGFR T790M Status and Progression Patterns During Initial EGFR-TKI Treatment in Patients Harboring EGFR Mutation

Aim: To assess time-to-treatment failure (TTF) in US patients with epidermal growth factor receptor ( EGFR) mutation-positive non-small-cell lung cancer (NSCLC) who received sequential afatinib–osimertinib treatment in the global, observational GioTag study. Patients & methods: Patients had EGFR T790M mutation-positive disease after first-line afatinib and subsequently received osimertinib. The primary outcome was TTF. Results: In 129 patients at US centers, median TTF was 28.4 months (90% CI: 27.0–34.1). Median overall survival was 47.6 months (90% CI: 35.5–51.5). Conclusion: Sequential afatinib–osimertinib in this US-treated population was associated with long median TTF and represents an effective, evidence-based treatment option for US patients with EGFR mutation-positive NSCLC not presenting with active brain metastases or de novo T790M. Clinical Trial Registration: NCT03370770 (ClinicalTrials.gov)

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141PD A prospective study of molecular testing status in the EGFR mutation positive NSCLC patients with disease progression during EGFR TKI treatment (REMEDY study)

Journal of Thoracic Oncology ◽

10.1016/s1556-0864(18)30415-5 ◽

2018 ◽

Vol 13 (4) ◽

pp. S82-S83 ◽

Cited By ~ 1

Author(s):

K. Kanai ◽

N. Yamamoto ◽

N. Nogami ◽

S. Atagi ◽

H. Saka ◽

...

Keyword(s):

Prospective Study ◽

Disease Progression ◽

Egfr Mutation ◽

Molecular Testing ◽

Tki Treatment ◽

A Prospective Study ◽

Nsclc Patients ◽

Egfr Tki

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Quantitative detection of the T790M EGFR mutation in circulating tumor DNA of lung cancer patients subjected to EGFR-TKI treatment.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.7594 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 7594-7594

Author(s):

J. Uchida ◽

K. Taniguchi ◽

F. Imamura ◽

K. Nishino ◽

T. Kumagai ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Egfr Mutation ◽

Circulating Tumor Dna ◽

Quantitative Detection ◽

Lung Cancer Patients ◽

Tki Treatment ◽

Egfr Tki ◽

Tumor Dna

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Changing causes of death post-epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) era in patients with advanced non-small cell lung cancer (NSCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e18132 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e18132-e18132

Author(s):

Wen Shuo Wu ◽

Yuh-Min Chen ◽

Chun-Ming Tsai ◽

Jen-Fu Shih ◽

Yu-Chin Lee ◽

...

Keyword(s):

Causes Of Death ◽

Hospice Care ◽

Egfr Mutation ◽

Kinase Inhibitor ◽

Cns Metastases ◽

Mutation Status ◽

Tki Treatment ◽

Nsclc Patients ◽

Egfr Tki ◽

Egfr Tkis

e18132 Background: EGFR-TKIs are effective against tumor EGFR-mutated NSCLC. Patients with tumor EGFR activating mutation (EGFRmu) (exon 19 deletions or exon 21 L958R) had better survival than those with EGFR wild-type tumors (EGFRwt). Many EGFRmu patients have had disease progression with EGFR-TKI treatment due to central nervous system (CNS) metastases, including meningeal carcinomatosis. The objective of this retrospective study is to compare the causes of death in patients with a known tumor EGFR mutation status who had been treated with EGFR-TKIs. Methods: We retrospectively reviewed the chart records of our advanced NSCLC patients who had received diagnosis, treatment, and supportive and hospice care in our hospital between July 2005 and June 2010. Tumor EGFR mutation status was analyzed using the DNA sequence method. All enrolled patients had a documented cause of death. Results: Ninety-four patients had documented tumor EGFR data, had received EGFR-TKI treatment (either erlotinib or gefitinib), and were with or without previous or salvage systemic chemotherapy. Of them, 36 were EGFRwt and 58 were EGFRmu. Overall survival after starting EGFR-TKI treatment was significantly longer in EGFRmu than in EGFRwt patients (median 68.9 weeks vs. 46.3 weeks, p=0.0058). Twenty-nine patients died of CNS metastases and 65 died of organ(s) failure other than the CNS. Patients who died of CNS metastases had undergone EKGF-TKI treatment significantly longer than those who died of other organ(s) failure (median 32 weeks vs. 7.7 weeks, p=0.0003), with a hazard ratio of 2.308 (95% C.I. 1.452-3.668, p=0.0004). A significantly higher proportion of EGFRmu patients died of CNS metastases (26 of 58, 44.8%) than EGFRwt patients (3 of 36, 8.3%) (p<0.001). Conclusions: EGFRmu NSCLC patients survived longer and had a significantly higher probability of mortality due to CNS metastases than EGFRwt patients. This change in the causes of death due to NSCLC was noted after an era of EGFR-TKI treatment, and will have an important impact on the strategies or management of patient supportive and hospice care.

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Trastuzumab and paclitaxel in patients (pts) with EGFR mutated non-small-cell lung cancer (NSCLC) that express HER2 after progression on EGFR TKI treatment.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.9042 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 9042-9042 ◽

Cited By ~ 6

Author(s):

Joop De Langen ◽

Justine Leonie Kuiper ◽

Erik Thunnissen ◽

Sayed MS Hashemi ◽

Kim Monkhorst ◽

...

Keyword(s):

Egfr Mutation ◽

Objective Response ◽

Her2 Expression ◽

Her2 Positive ◽

Open Label ◽

Tumor Biopsy ◽

End Point ◽

Tki Treatment ◽

Tumor Biopsies ◽

Egfr Tki

9042 Background: HER2 expression as well as amplification has been well recognized in tumor biopsies of pts with an EGFR mutation who developed EGFR TKI resistance. It is unknown whether HER2 targeting in this setting can result in tumor responses. Methods: Single arm open label phase II study to study the safety and efficacy of paclitaxel-trastuzumab treatment in pts with a sensitizing EGFR mutation who show tumor membrane HER2 expression in a tumor biopsy (immunohistochemistry (IHC) ≥1) after progression on EGFR TKI treatment. Paclitaxel (60 mg/m2) and trastuzumab (first dose 4 mg/kg, thereafter 2 mg/kg) were dosed weekly until disease progression or unacceptable toxicity. Primary end-point was tumor response according to RECIST. Sample size of 20 pts was calculated to evaluate the primary objective of ≥30% objective response rate. The study was deemed positive when ≥7 pts would show a partial or complete response. Results: 21 pts were enrolled from 08-2012 to 02-2017. 7 pts were exon 21 L858R positive and 14 exon 19 del. Last TKI was erlotinib (n = 6), gefitinib (n = 4), rociletinib (n = 3) or osimertinib (n = 8). Median HER2 IHC was 2+ (range 1-3). 17 pts were evaluable for response assessment, while 4 pts are awaiting their first response scan. The primary end-point was met with 7/17 pts (41%) showing a partial response. 2 pts showed stable disease, 7 progressive disease and 1 pt had clinical progression before CT response evaluation. Median duration of response was 9 (range 6-18) months with one ongoing responder. 3 pts experienced grade ≥3 toxicity, including fatigue, neuropathy and neutropenia. Upon progression on study treatment, all responding pts were rebiopsied. 4/6 samples were negative for HER2 (IHC), suggesting that the combination effectively targeted HER2 positive tumor cells. Conclusions: The study met its primary end-point. Paclitaxel-trastuzumab induces durable objective tumor responses in EGFR TKI pretreated pts with an activating EGFR mutation and HER2 bypass track activation. The treatment was well tolerated. Post-progression tumor biopsies showed absence of HER2 staining in the majority of pts, suggesting effective HER2 targeting. Clinical trial information: NCT02226757.

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