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Hanping Wang
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 2
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-041 - The Concentration of Avitinib in Cerebrospinal Fluid and Its Efficacy and Safety in NSCLC Patients with T790M Mutation (ID 9458)
09:30 - 09:30 | Presenting Author(s): Hanping Wang
- Abstract
Background:
Avitinib is an oral, potent, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor selective for T790M resistance mutations. We report the safety, the intracranial/extracranial efficacy, and the blood brain barrier (BBB) penetration rate of Avitinib in non-small cell lung cancer(NSCLC) patients with EGFR T790m mutation. The data come from Peking Union Medical College hospital-a single center of the Phase 1, open-label, multicenter study (NCT02330367).
Method:
NSCLC Patients with acquired EGFR T790m (+) were enrolled. Patients were orally administered with dose escalating from 150 mg to 300 mg twice daily for 28-continuous-day cycles until disease progression. Blood (2mL) and cerebrospinal fluid (CSF) samples (2ml) were collected for concentration analysis on day 29 in available patients with brain metastases (BM). Tumor response was assessed on day 29 and then every 8 weeks.
Result:
Sixteen patients were included. Nine patients had asymptomatic BM, and all the nine patients had more than 3 BM lesions. The most frequent adverse events were the elevated hepatic transaminases (10/16, 62.5%) and diarrhea (5/16, 31.3%), Most were mild and reversible. 9 Patients (56.3%) achieved Partial Response (PR), 6 (37.5%) achieved Stable Disease (SD). Median Progress Free Survival (PFS) was 247 days (95%CI: 154.8-339.2), and the Median Overall Survival (OS) was 536 days (95%CI: 363.6-708.4). Of the 7 evaluable BM patients, the median intracranial PFS was 142 days (95% CI 31.1-252.9), with two patients progressed first in intracranial disease, while five patients had concurrent intracranial and extracranial progression after avitinib treatment. The cytologic analysis of CSF showed one meningeal metastases who accepted intrathecal injection with methotrexate and dexamethasone later. The blood and CSF analysis of 5 BM patients showed the BBB penetration rate were 0.046%-0.146% (Table).
[1]Her BBB was broken by postocular metasatses. [2]He accepted brain radiotherapy before avitinib, and he also accepted chemotherapy with pemetrexed plus carboplatin plus endostatin after progression from avitinib. He was excluded from the analysis of intracranial PFS.patients CSF Con. (ng/ml) Plasma Con. (ng/ml) Per.% Intracranial PFS (days) Extracranial PFS (days) 1 0.106 231 0.046 566 566 2 0.425 291 0.146 60 177 3 0.487 631 0.077 142 142 4 4.05 2940 0.138 138 138 5 1.72 1890 0.091 28 28 6 24 227 10.6[1] 218 218 7 308 350 8 550[2] 252
Conclusion:
Avitinib is well tolerated and efficacious in EGFR T790m(+) NSCLC patients. Its concentration in CSF is low, and the penetrability of BBB is weak. The median intracranial PFS for asymptomatic BM is relative short comparing to extracranial disease. Further studies are proceeding.
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P2.03-050 - The Efficacy of EGFR Tyrosine Kinase Inhibitors in Advanced Non-Small Cell Lung Cancer Harboring G719X Mutation (ID 9927)
09:30 - 09:30 | Presenting Author(s): Hanping Wang
- Abstract
Background:
Few uncommon EGFR mutations existed in NSCLC patients, such as G719X mutation on 18 exon. The best treatment option for G719X mutation is unclear, and it is usually excluded from clinical trials using EGFR TKI therapy. Here we studied the clinical data of patients harboring G719X mutation in real world and their sensitivity to EGFR TKIs.
Method:
Between January 2011 and December 2016, we retrospectively collected the clinical data of stage IIIB/IV NSCLC patients harboring G719X mutation at Peking Union Medical College Hospital.
Result:
A total of 830 NSCLC patients were found to harbor common sensitive EGFR mutations ( 417 patients harbored 19 exon deletion，413 patients harbored 21 L858 mutation, respectively), while 27 (27/857, 3.15%) patients harbored G719X mutation on 18 Exon, using amplification refractory mutation system (ARMs). 19 (19/27, 70.4%) patients with G719X mutation were treated with EGFR TKIs, 11 (57.9%) with Gefitinib, 5 (26.3%) with Icotinib, and 3 (15.8%) with Erlotinib, respectively. The median age was 58.3 years ( range from 30 to 79 years). There were 11(57.9%) females, and 6 (31.6%) patients with history of heavy smoking. 3 (15.8%) patients had baseline central nervous systemic metastasis. 11(57.9%) patients had unique G719x mutation, while 8 patient had compound mutations (5 patients had G719+20s768I, 2 patients had G719+L861Q, and 1 patient had G719+19del). 9 (47.4%) patients gained PR, 7 (36.8%) patients gained SD, and 3 (15.8%) achieved PD, the ORR was 47.4%, and the DCR was 84.2%. The median PFS was 8.8 months (95% CI: 0.932-16.67). The median PFS of first-line TKI therapy was longer than second-line TKI therapy (10.8months vs. 4.0months respectively), but it didn’t got statistical significance (p=0.226). The median OS was 15.3 months (95%CI: 12.3-18.3), with 6 patients still alive. There were no intolerant adverse effect associating with EGFR TKIs.
Conclusion:
These results suggest that EGFR TKI therapy is effective in patients with G719X mutations. EGFR TKI could be a treatment choice better than chemotherapy for patients harboring G719X mutation.
