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Albina Zhabina
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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-49 - The Role of ctDNA Detection (Liquid Biopsy) in Patients with NSСLC (ID 2617)
09:45 - 18:00 | Presenting Author(s): Albina Zhabina
- Abstract
Background
The analysis of the circulating tumor DNA has attracted interest in the last 6-7 years and is being actively introduced into everyday practice. "Liquid biopsy" will eliminate the shortcomings of routine biopsy, accelerate the time of clinical decision-making, to conduct a more comprehensive study of the tumor in terms of personification of treatment and development of resistance. Results of liquid biopsy provide real-time information on the molecular pathologies and morphological features, identify early resistance to treatment and can modify the therapy regimen.
Method
From 2016 to 2018 year we studied patients with NSСLC. The ctDNA was detected in the baseline plasma samples and then every 2 months after treatment started by RT-PCR. The aim of the study was to assess the relationship between the presence of EGFR positive ctDNA in tumor tissue and blood plasma
Result
The study was 1050 patients, 462 cases are represented by adenocarcinoma of NSCLC. EGFR mutations was detected in 145/462 cases (31.38%). Among 145 person 109 were women (72.5%) and 36 were men (24.8%). The mean age was 65.18 (35 - 85). The mutational profile was heterogeneous: ex19del – 94/145 (63.8%), L858R – 47/145 (32.4%), others – 4/145 (2.8%). The results of the study demonstrated that analyzing ctDNA from plasma is feasible for the identification of EGFR mutations with mutation status concordance in 79 matched samples of 53.2% (EGFR mutation positive was detected in 42/79 samples).
The T790m resistance mutation was detected in the baseline plasma sample in 8/79 cases (10.1%). EGFR-activating mutations were identified in 13/56 (23.3%) plasma samples after 2 months of Gefitinib.
Among the 42 patients in whom the сtDNC was detected in the baseline, after 2 months of therapy was determined only in 6/42 (14.2%). Thus, the disappearance of the mutation was observed in 85.71% (36/42). Mediana of PSF for patients who retained ctDNA after 2 months was 16.25 months (Cl 95% 11.24 – 19.94), and for patients in whom the mutation disappeared after 2 months was 21.10 (Cl 19.21 - 22.98).
Currently the study of molecular genetic markers in blood plasma are continuing. The relationship between effectiveness of treatment and ctDNA detection in blood samples will be analyzed.
Conclusion
This new, minimally invasive method has the potential to change the prognostic and predictive landscape for lung cancer genotyping and patient management, which will improve treatment outcomes
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-30 - Predictive Value of ctDNA in Patients with EGFR Positive NSCLC Receiving 3rd Generation TKI (ID 1954)
10:15 - 18:15 | Author(s): Albina Zhabina
- Abstract
Background
The third generation TKI (osimertinib) according to AURA III trial results achieved longer PFS compared to standard platinum based chemotherapy in patient’s resistant to 1-2 generation TKIs due to T790M mutation (8.5 vs 4.2 months). The evolution of resistance profile during thins therapy can be analyzed based on ctDNA.
Method
In this study patients with metastatic EGFR mutated NSCLC, with a confirmed disease progression during treatment with 1/2 generation TKIs, T790M positive which included patients received osimertinib 80 mg daily. Before the treatment and then every 2 months, whole blood was taken, for qualitative assessment of ctDNA dynamics by RT-PCR. The aim of the study was to assess the relationship between the disappearance of T790M + ctDNA and the time to progression on osimertinib.
Result
From August 2016 to December 2018 22 patients with T790M positive progression were identified. 18/22 (81.9%) were women, 4/22 (18.1%) - men. The mean age was 61.2 years (50-75). Only 1/22 had a smoking history > 30 pack/years. Primary activating mutations in EGFR gene were ex19del, L858R and G719S + S768I in 16, 5 and 1 patients respectively. Median PFS on the first line TKI was 21.7 months (CI 95%, 10.8 – 53.3). In 59.1% (13/22) progressive disease was characterized by the appearance of new metastases and in 40.9% (9/22) by the growth of previously identified metastases. 22 patients were evaluable for response. PR and SD were achieved in 11/20 (50%) and 10/20 (45/5%) respectively. Median PFS was in a whole group 16.7 months (CI 95%, 11.4 - 22.0). T790M in ctDNA was negative after 2 months of osimertinib treatment in 12/22 patients. Median PFS was 18.9 months (CI 95%, 14.8–19.7) in patients with undetectable T790M in ctDNA after 2 month of therapy compared to 8.0 months (CI 95%, 4.2 – 11.8) in patients remaining ctDNA T790M positive. No clinical factors were associated with the disappearance of ctDNA by statistical analysis.
Conclusion
The disappearance of T790M + ctDNA after 2 months osimertinib therapy is predictive of greater PFS in patients with EGFR mutation positive NSCLC, receving of 2nd line.
