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Hye Ryun Kim
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MA 11 - Emerging Diagnostic/Biomarkers in NSCLC (ID 668)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:M.I. Abdul Wahid, Martin Reck
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 313 + 314
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MA 11.04 - Discussant - MA 11.01, MA 11.02, MA 11.03 (ID 10811)
11:15 - 11:30 | Presenting Author(s): Hye Ryun Kim
- Abstract
- Presentation
Abstract not provided
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MA 11.09 - Real World Data of Rebiopsy, Mutation Status, and Its Association with Plasma Genotyping after EGFR TKI Failure in NSCLC (ID 8234)
12:00 - 12:05 | Author(s): Hye Ryun Kim
- Abstract
- Presentation
Background:
After the introduction of third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in non-small cell lung cancer (NSCLC), the second tumor biopsy and EGFR mutation test to confirm T790M status is an established standard practice. But second biopsy is invasive, cost and time-consuming and occasionally impossible. We aimed to investigate the success rate of tissue rebiopsy and incidence of T790M mutation in tissue and plasma at the time of progression with earlier-generation EGFR TKIs in real world setting. Also, we studied the association between the efficacy of osimertinib and the status of tissue and/or plasma T790M mutation.
Method:
We analyzed patients who were screened and enrolled into ASTRIS trial in Yonsei Cancer Center (NCT02474355). Key inclusions were advanced/metastatic NSCLC with tissue and/or plasma T790M mutation and prior EGFR-TKI therapy. Tissue and plasma EGFR mutation tests were performed using PNAClamp[TM] and PANAMutyper[TM], respectively.
Result:
We screened 193 patients with NSCLC harboring EGFR-activating mutation who experienced disease progression upon earlier-generation EGFR TKIs during study period. The second biopsy including tissue and/or cytology was performed only in 60.1% of the patients (116/193) and the success rate was 86.2% (100/116). The reasons for not trying a biopsy were as follow: inaccessibility (n=25), poor PS (n=8), previously reported plasma T790M+ (n=8), and patients’ refusal (n=4). The parenchymal lung tissue (n=61) was most commonly targeted lesion and bronchoscopy was the most frequently used method (n=35). Six patients underwent video-assisted thoracoscopic surgery. Tumor T790M mutation was reported in only 25.9% of patients (50/193). Of 193 patients, 88 patients were enrolled into ASTRIS trial and 43 patients were registered based on the plasma test only. With a median follow-up of 25.1 weeks, the objective response rate (ORR), median progression-free survival (PFS), and duration of the response (DoR) were 44.3%, 32.7 weeks, and 27.0 weeks, respectively. Median overall survival (OS) was not reached. The ORR, median PFS and DoR of tumor T790M+ (n=45) vs. plasma T790M+ (n=54) were 57.8% vs. 35.2%, 45.0 vs. 20.4 weeks, and 26.3 vs. 25.9 weeks, respectively.
Conclusion:
With the increasing importance of tissue rebiopsy after EGFR-TKI failure, there is a growing interest to overcome the challenge of subsequent biopsy. Even though relatively lower ORR and shorter PFS in patients with plasma T790M+ compared with tissue T790M+, the plasma EGFR genotyping may be good alternative to the tissue biopsy in consideration of long DoR when treated with osimertinib and low yield rate of tissue T790M testing.
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MA 12 - Circumventing EGFR Resistance (ID 665)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Wan Ling Tan, Nobuyuki Yamamoto
- Coordinates: 10/17/2017, 11:00 - 12:30, F205 + F206 (Annex Hall)
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MA 12.01 - A Phase Ib Study of the Combination of Afatinib and Ruxolitinib in EGFR Mutant NSCLC Progressed on EGFR-TKI: An Updated Analysis (ID 9021)
11:00 - 11:05 | Author(s): Hye Ryun Kim
- Abstract
- Presentation
Background:
T790M mutation of EGFR exon 20 is observed in approximately 50% of the non-small cell lung cancer (NSCLC) patients progressed on EGFR tyrosine kinase inhibitors (TKIs). Based on a preclinical study demonstrating that pharmacologic JAK1 inhibition increased the anti-tumor activity of afatinib in T790M-positive NSCLC cell lines, we conducted a phase Ib study to evaluate the safety and efficacy of the combination of afatinib and ruxolitinib, a selective JAK inhibitor, in NSCLC patients who had progressed on EGFR-TKIs.
Method:
We used the classical 3+3 design for dose-escalation cohort (DAC). Patients with histologically diagnosed, EGFR mutant stage IV NSCLC and documented disease progression on EGFR-TKIs were considered eligible. Afatinib was administered alone once daily from day 1 through day 8 (run-in period), then ruxolitinib was orally administered twice daily concomitantly with afatinib until progression. The primary endpoint was to determine RP2D and DLT. If DLT was not observed in 9 patients at the cohort of the highest level, we planned to decide RP2D and enroll 6 additional patients in the dose-expansion cohort (DEC).
Result:
As of June 14, 2017, 21 patients (12 with exon19 deletion, 9 with exon21 L858R) were enrolled in DAC, 8 of which had T790M mutations. All patients were previously treated with erlotinib (n=6) or gefitinib (n=15), and previously received a median of 2 (range, 1-4) lines of chemotherapy. Because no DLT was observed in the 9 patients at the highest dose level (afatinib 50 mg once daily plus ruxolitinib 25 mg twice daily), 6 patients with T790M mutation were enrolled in the DEC. Frequent AEs included paronychia (G1 in 11 cases, G2 in 2 cases), diarrhea (G1 in 14 cases, G2 in 2 cases, and G3 in 2 cases), acneiform rash (G1 in 13 cases), and oral mucositis (G1 in 7 cases, G2 in 3 cases). SAEs were reported in 6 patients, which were not related to the investigational products. Partial responses were observed in 7 patients (25.9%) with disease control rate (CR+PR+SD) of 96.3%. Median PFS was 5.7 months (95% CI, 4.2-7.2) and 3 patients remain on study.
Conclusion:
The combination of afatinib with ruxolitinib was well tolerated with clinical benefit of disease control in NSCLC with acquired resistance to EGFR-TKIs (NCT02145637).
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-028 - Efficacy of Osimertinib for Brain Metastasis in Advanced NSCLC: Data from Single Center in ASTRIS Trial (ID 9114)
09:30 - 09:30 | Author(s): Hye Ryun Kim
- Abstract
Background:
CNS (central nervous system) involvement is common in advanced NSCLC (non-small cell lung cancer). Osimertinib has shown activity in CNS in preclinical studies and phase II, III trials (AURA2, AURA3). We reported the efficacy of CNS metastases from an open label, multinational, multicenter, real world treatment study (ASTRIS, NCT02474355) in patients with T790M-positive advanced NSCLC who have progressed on or after prior epidermal growth factor receptor-tyrosine-kinase inhibitors (EGFR-TKI) therapy.
Method:
Patients with T790M-positive (from tissue, plasma or other fluids) advanced NSCLC received osimertinib 80mg once daily. Of the 88 patients who were enrolled in ASTRIS at Yonsei Cancer Center, 10 patients who did not have baseline brain workup and 15 patients without CNS metastases at the beginning of study were excluded from this analysis. A subgroup analysis was conducted in patients with CNS metastases at the baseline, as assessed by neuroradiologist, to define CNS overall response rate (ORR), duration of response (DOR), and progression-free-survival (PFS) by RECIST(Response Evaluation Criteria in Solid Tumors) v1.1. The CNS full analysis set (cFAS) included patients with ≥ 1 measurable and/or non-measurable CNS metastasis present on baseline scan; the CNS evaluable for response set (cEFR) included only patients with ≥ 1 measurable CNS metastasis.
Result:
Among the 63 patients who had CNS metastases at baseline, fifty-four (61.4%) patients were included in the subgroup analysis as cFAS, except for the 9 patients who did not follow up brain image during ASTRIS. In patients without brain metastases at the time of initiation of osimertinib (n=15), no experienced CNS progression during ASTRIS. CNS ORR was 81.3% (95% confidence interval [CI] 73.2-89.4) in the cEFR and 40.7% (95% CI 30.4-50.9) in the cFAS. In the cEFR and cFAS, median CNS DOR was “not reached” vs 40.1 weeks (95% CI 36.95-43.25). The median CNS PFS was not reached in both cFAS and cEFR. CNS ORR of 33.3%(95% CI 11.7-64.9) and 42.2% (95% CI 28.9-56.7) were observed for patients with CNS metastases within 3 months brain radiation and without prior radiation or ≥ 3months brain radiation, increasing to 75.0% (95% CI 28.9-96.6) and 83.3%(95% CI 54.0-96.5) respectively, for patients with measurable CNS disease only. CNS ORR of T790M-positive patients in tissue and plasma were 37.5%(95% CI 21.1-57.4) and 46.4% (95% CI 29.5-64.2) in the cFAS, vs 100%(95% CI 55.7-100.0) and 70.0%(95% CI 39.2-89.7) in the cEFR.
Conclusion:
Osimertinib had good CNS efficacy irrespective of radiation history in T790M-positive advanced NSCLC.
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P3.03 - Chemotherapy/Targeted Therapy (ID 719)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.03-021 - In Vitro Pharmacogenomic Platform with a High-Purity Patient-Derived Cell Model (ID 9850)
09:30 - 09:30 | Author(s): Hye Ryun Kim
- Abstract
Background:
We have developed a high-purity patient-derived cell (HP-PDC) method for primary culture of malignant effusions from non-small cell lung cancer (NSCLC) patients with oncogenic driver mutations. We updated the results of HP-PDC with mutation test and drug response.
Method:
HP-PDCs were established by a multistep isolation protocol. Malignant effusions were cultured and examined with a light microscope to identify spheroid-forming cells. Immunofluorescence (IF) and flow cytometry were used to evaluate the purity of tumor cell in PDCs. EGFR, ALK or ROS mutation of PDCs was analyzed with direct or PCR-based sequencing and RT-PCR. The sensitivity of target agent to HP-PDCs were tested using a cell viability assay.
Result:
Consecutive series of 79 malignant effusion samples was collected from 61 patients with advanced NSCLC. Spheroid-forming cells were detected in 41 samples which were cultured in AR5 media to establish PDCs. IF analysis revealed that TTF-1 was upregulated in 17 PDCs (21.5%), which also showed EpCAM-positive cell population in flow cytometry with high purity of over 70%. Time spent for establishment of HP-PDCs ranged from 26 days to 132 days. There were 9 PDCs (53%) which harbored active EGFR mutations. Three PDCs with ALK fusion and four with ROS1 fusion were established. Twelve PDC cases were from patients who experienced disease progression while on treatment with EGFR- (9) and ALK- (3) tyrosine kinase inhibitors. Four PDCs with ROS1 fusion were obtained before anti-cancer treatment. Three of PDCs with EGFR mutations were established from patients, who progressed on both gefitinib and the 3[rd] generation EGFR inhibitors. All of them showed in vitro resistance to both gefitinib and 3[rd] generation EGFR inhibitors. PDC from a patient with ROS1 fusion was sensitive to ROS1 inhibitors (entrectinib, crizotinib and ceritinib) in vitro test. The patient has been treated with entrectinib and showed partial response.
Conclusion:
HP-PDCs provide useful in vitro platforms of preclinical studies which predicts responses to targeted therapies in a short period of time and may provide an excellent platform for personalized therapies in NSCLC patients.
