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MO21 - Prognostic and Predictive Biomarkers V - EGFR (ID 98)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
MO21.03 - Variability of epidermal growth factor receptor (EGFR) mutations in serum during erlotinib therapy and its clinical implications: exploratory analysis of a phase II study of erlotinib in patients with advanced non-small-cell lung cancer (NSCLC) harboring EGFR mutations (ID 2719)
10:30 - 12:00 | Author(s): N. Ohishi
Erlotinib is a standard treatment for NSCLC patients harboring EGFR mutations. Many tumors acquire resistance mutations during erlotinib treatment; consequently, confirmation of EGFR mutation status is important to select appropriate subsequent therapy after progression. Obtaining tumor samples is not easy, therefore, serum samples are more applicable for this purpose. This analysis measured serum EGFR mutations before and after administration of erlotinib in a phase II study in Japanese chemotherapy-naïve patients with advanced NSCLC harboring EGFR mutations (JO22903).
We analysed serum samples from patients in the JO22903 study by Scorpion-ARMS to confirm the presence of EGFR mutations before and after erlotinib administration (190 days post treatment initiation and at disease progression). The mutation results were evaluated in relation to clinical characteristics and effects of erlotinib.
Of the 103 patients registered in JO22903, 95 consented to the examination of EGFR mutations in serum samples prior to and following administration of erlotinib. Of these 95 patients, 26 were positive for EGFR mutations (16 were exon 19 deletions, nine were exon 21 L858R mutations, one was an exon 20 S768I mutation). In the 26 patients classed as EGFR mutation-positive in serum samples, the concordance rate between tumor samples and serum samples was 96.2% (matching 25 cases except the S768I mutation case). The EGFR mutation detection rate in serum samples prior to erlotinib administration was 35.6% for exon 19 deletions (16/45) and 18.0% for L858R mutations (9/50). In six cases where exon 20 T790M or minor mutations were detected alongside major mutations in tumor samples, the major mutations were detected in corresponding serum samples of four patients but the T790M mutations or minor mutations were not detected in any serum samples. In the 65 cases in which serum samples were taken 190 days after erlotinib administration, five were positive for EGFR mutations (exon 19 deletions in four, and L858R in one). Four of these cases were consistent with the mutation type of the tumor samples taken before erlotinib administration; one case changed from L858R to exon 19 deletion. Serum samples at disease progression were taken for 72 patients. Of these, 16 were positive for EGFR mutations (three were exon 19 deletions, five were exon 19 deletions + T790M, six were L858R and two were L858R + T790M). EGFR mutation type had changed after administration of erlotinib in three cases; these cases also had multiple metastases. Characteristics of EGFR mutation-positive cases in the pre-treatment serum samples were large tumor size, and metastases to other organs (bone, brain, liver). Patients with baseline serum EGFR mutations had median PFS of 9.7 months and those without baseline serum EGFR mutations had median PFS of 15.2 months. Further efficacy results will be presented.
The sensitivity of these analyses was not enough to draw firm conclusions; however, results show the possibility that serum EGFR mutations correlate with disease activity and emergence of resistance mutations. Further study is recommended to measure serum EGFR mutations throughout the treatment course, to ascertain whether this can predict the risk of disease progression.
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