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T. Tokito
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-091 - Digital PCR Analysis of Plasma Cell-Free DNA as a Noninvasive Detection of the Drug Resistance Mechanisms in EGFR Mutant NSCLC (ID 2613)
09:30 - 09:30 | Author(s): T. Tokito
- Abstract
Background:
Although the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have shown dramatic effects against EGFR mutant non-small-cell lung cancer (NSCLC), patients demonstrate resistant by various mechanisms, such as second-site point mutation that substitutes methionine for threonine at position 790 (T790M) in EGFR, and amplification of mesenchymal-epithelial transition (MET) proto-oncogene and human epidermal growth factor receptor 2 (HER2). With the development of overcoming resistance to EGFR-TKIs, identification of the mechanisms of drug resistance is urgently needed. However, tumor samples for detecting the resistant mechanisms were not easily available in patients with EGFR mutation-positive NSCLC relapsed after EGFR-TKIs treatment. Here, we examined the correlation of T790M mutation, activating EGFR mutations, HER2 amplification, and MET amplification in relapsed NSCLC patients between plasma and tumor samples using digital PCR assay as an alternative and noninvasive method.
Methods:
A total of 18 patients obtained pairs of tumor and blood samples after resistance to EGFR-TKI treatment were enrolled in this study. T790M mutation, activating EGFR mutations, MET amplification, and HER2 amplification in relapsed NSCLC patients after EGFR-TKIs treatment were analyzed by digital PCR.
Results:
Digital PCR analysis of T790M mutation in plasma had a sensitivity of 81.8% and specificity of 85.7%, with the overall concordance between plasma and tissue samples 83.3%. Analysis of primary active mutation in plasma showed inconsistent results with lower sensitivity of 66.7% and concordance of 70.6% compared to those of T790M mutation. MET gene copy number gain of tumor DNA by digital PCR was observed in three patients. Of these patients, one patient exhibited positive for MET amplification by FISH, whereas no patient demonstrated MET and HER2 copy number gain in plasma DNA.
Conclusion:
Digital PCR analysis in plasma is feasible and accurate method for detecting the T790M mutation in NSCLC resistance to EGFR-TKIs treatment.
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-068 - Phase II Study of S-1 plus Bevacizumab for Pretreated Patients with Non-Squamous NSCLC (ID 677)
09:30 - 09:30 | Author(s): T. Tokito
- Abstract
Background:
The additional effects of bevacizumab (B) as first-line chemotherapy for non-squamous non-small cell lung cancer (Non-sq NSCLC) have been established. However, the efficacy of B in a second-line setting or further has not been clarified. It has recently become clear that S-1 (S), an oral fluoropyrimidine, is effective for advanced NSCLC, and S is now used with platinum as one of the standard forms of first-line chemotherapy. Furthermore, preclinical findings have suggested that the combination of S plus B is a promising treatment option.
Methods:
Non-sq NSCLC patients with an ECOG performance status of 0-2, and who had undergone prior platinum-based chemotherapy regardless of the use of B, were eligible for the study. S (80 mg/m[2]) was administered orally twice daily for 14 days, and B (15 mg/kg) on day 1 every 3 weeks until disease progression or unacceptable toxicity occurred. The primary endpoint was progression-free survival (PFS), and the planned sample size was 28 patients.
Results:
Between March 2012 and June 2014, 28 patients (14 males and 14 females; median age 62 years; PS 0/1/2: 21/7/0; Ad/Other: 26/2, EGFR mutation positive/wild type 12/16) were accrued from 4 centers in Japan. All 28 patients were included in analysis of efficacy and toxicity. With a median follow-up of 9.3 months, the median PFS was 3.2 months (95% CI: 2.2-4.0 months). Patients who had not received prior pemetrexed or who had shown a good response to prior chemotherapy tended to have a longer PFS (5.3 and 5.0 months, respectively), although this was not statistically significant. An objective response was observed in 4 patients (PR; 4, SD; 20, PD 4), the response rate and disease control rate being 14.3% and 85.7%, respectively. The treatment was well tolerated, the most common treatment-related side effects being anorexia (75%) and fatigue (68%).
Conclusion:
This is the first report to evaluate the efficacy and safety of SB. Although SB seems to have a higher tumor reduction effect than S alone for previously treated Non-sq NSCLC, this study failed to meet its primary endpoint. SB is well tolerated and no new toxicities were observed.
