Virtual Library
Start Your Search
Akito Hata
Author of
-
+
EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
-
+
EP1.01-13 - A Phase 2 Trial Assessing Osimertinib Activity Against Leptomeningeal Carcinomatosis in EGFR-Mutant Lung Cancer (Now Available) (ID 470)
08:00 - 18:00 | Author(s): Akito Hata
- Abstract
Background
Leptomeningeal carcinomatosis (LMC) occurs in 10 % of EGFR-mutant lung adenocarcinoma (LA). Retrospective studies have suggeted a clinical benefit of osimertinib in treating LMC in patients with EGFR-mutant LA. We conducted a phase 2 prospective trial to demonstrate the clinical efficacy, activity, and LMC-specific mechanisms of resitance to osimertinib in EGFR-mutant LA patients.
Method
We performed gadalidium-enhanced brain MRIs at the time of enrollment, followed by scheduled brain imaging once every six weeks. Clinical neurological exams were performed every four weeks. Adverse Events (AEs) were assessed by NCI-CTCAE Ver. 4. Cerebral spinal fluid (CSF) and plasma was obtained on day 1 and 21 for all patients. The CSF osimertinib penetration rate was measured by liquid-chromatography mass spectrometry (LC-MSMS) and compared to plasma osimertinib levels. Targeted droplet digital PCR (ddPCR) was used to detect copy number changes of Met and the EGFR C797S mutation in patients CSF-DNA and plasma cell free (cf) DNA.
Result
We enrolled six pre EGFR-TKI treated EGFR mutant LA with LMC. We observed a LMC-specific progression free survival of 3.7 months and overall survival of 6.2 months or longer with osimertinib. Four and three of six patients showed neurological and radiological responses, respectively. No patients had any AEs greater than grade 3 and all patients continued osimertinib beyond PD. The osimertinib CSF penetration rate was 1.2±0.5%. Met copy number was normal in plasma, but increased in the CSF of 2/6 patients prior to progression. Met copy number was confirmed in 1/6 patients at the time of progression. An aquired EGFR C797S mutation was observed in 1/6 patients prior to progression.
Conclusion
Osimertinib 80 mg is efficacious in the treatment of LMC in EGFR mutated LA. CSF-specific MET copy number gain and EGFR C797S mutations arise prior to progression in EGFR-mutant LA patients treated with osimeritinib.
-
+
P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.01-04 - A Phase II Trial of Weekly Nab-Paclitaxel in the Salvage Setting for Advanced Non-Small Cell Lung Cancer: Results of NICE Salvage Study (ID 1534)
09:45 - 18:00 | Author(s): Akito Hata
- Abstract
Background
The optimal treatment in patients with advanced non-small cell lung cancer (NSCLC) after failing second- or third-line chemotherapy, i.e. NSCLC in salvage setting, has yet to be established. A small study reported that solvent-based paclitaxel (sb-P) monotherapy was safe and efficacious and could be a treatment option for NSCLC in salvage setting (Anticancer Res 2005). Nanoparticle albumin-bound paclitaxel (nab-P) showed a higher overall response rate (ORR) and better tolerability than sb-P when combined with carboplatin (CBDCA) as a first-line chemotherapy (J Clin Oncol 2012). These results suggest that nab-P monotherapy could be better therapeutic option than sb-P monotherapy for NSCLC in salvage setting. We therefore planned NICE Salvage study aiming to assess the efficacy and safety of nab-P monotherapy for NSCLC patients in salvage setting.
Method
NICE Salvage study was a multicenter single arm phase II study. Eligibility criteria included patients aged >= 20 years, with PS 0-2 and adequate organ function, and who have failed two or three prior lines of chemotherapy including at least a platinum-containing regimen for pathologically-proven advanced NSCLC. Patients who had treatment history with sb-P or nab-P, or had tumors harboring EGFR mutation or ALK fusion gene were excluded. Nab-P was administered at a dose of 80 mg/m2 on days 1,8 and 15 of a 28-days cycle and repeated until progressive disease, unacceptable toxicity, or patient’s refusal. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), ORR, disease control rate (DCR), efficacy according to prior use of docetaxel, quality of life, and safety. The study is powered to detect a 1.5-month improvement in median PFS in the investigational arm beyond the 2.0-month median PFS estimated from historical data. Assuming a one-sided 0.10 level of Type I error and 80% power, target sample size is calculated at 35. (UMIN000016173).
Result
Thirty-eight patients were enrolled and a patient was excluded from efficacy and safety analysis. Patient’s characteristics (n = 38) were as follows: median age = 68 years, male/female = 31/7, adenocarcinoma/squamous cell carcinoma /others = 20/15/3. Median PFS and OS was 3.5 month (95% confidence interval (CI), 1.7-3.8), and 13.4 month (95%CI, 9.1-25.1), respectively. ORR and DCR were 10.8% (95%CI, 2.9-24.8 ) and 56.8% (95%CI, 38.3-71.3 ), respectively. Grade 3 or 4 treatment-related adverse events were neutropenia (10.8%), anemia (2.7%), hepatotoxicity (2.7%) and diarrhea (2.7%). One treatment-related death (pulmonary infection) was observed.
Conclusion
This study failed to meet predefined primary endpoint. However the results showed that nab-P monotherapy was moderately efficacious and well-tolerated, suggesting the need for further investigation for NSCLC in salvage setting.
