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J. Feng
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P2.03a - Poster Session with Presenters Present (ID 464)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03a-052 - Phase I Study and Pharmacokinetics of Paclitaxel Micelles for Injection in Chinese Patients with Advanced-Stage Malignancies (ID 3898)
14:30 - 14:30 | Author(s): J. Feng
- Abstract
Background:
Paclitaxel micelle for injection is a Cremophor-free, nanoscale, polymer micelles loaded paclitaxel formulation. The absence of Cremophor EL may permit Paclitaxel Micelle to be administered without the premedications used for the prevention of hypersensitivity reactions. The objective of this Phase I trial were to determine the toxic effects, maximum tolerated dose (MTD), Dose-limiting toxicity (DLT), pharmacokinetics(PKs) profile and recommended phase II dose of Paclitaxel Micelle.
Methods:
Dose escalation of paclitaxel micelle for injection followed the standard “3+3” rule, and started at does level 175 mg/m2. Eligible patients were treated with paclitaxel micelle given as a 3 h intravenous infusion on day 1 once every 3 weeks. Blood samples were collected to determine the PKs of paclitaxel micelle.
Results:
18 patients with advanced malignancies were enrolled and treated, including non-small cell lung cancer (NSCLC) 17 patients and breast cancer 1 patients. The dose of paclitaxel micelle for injection ranged from 175 mg/m2 (dose level 1) to 435 mg/m2 (dose level 5). All patients were evaluable for toxicity and antitumor response. The most common toxic reactions of paclitaxel micelles include neutropenia, peripheral nerve numbness and muscle pain, no acute hypersensitivity reactions were observed. DLT included grade 4 neutropenia, which occurred in 1 of 6 patients treated at 300 mg/m2 (level 3) and all of 3 patients at 435 mg/m2 (level 5), and grade 3 peripheral nerve numbness in 1 patient at 435 mg/m2 (level 5). The MTD was thus determined to be 390mg/m2 (level 4). Partial response was observed in 6 of 18 patients (33.3%), 3 of whom had prior exposure to paclitaxel chemotherapy. 9 patients (50%) had stable response and only 3 patients had disease progression. 18 patients completed 99 cycles of paclitaxel micelle chemotherapy (2~19 cycles), and now one patient at 390 mg/m2 (level 4) has been completed 19 cycles of chemotherapy and is still in treatment. The median PFS was 9.1months (95% CI,4.70-18.43). The paclitaxel Cmax and area under the curveinf values increased with escalating doses, which revealed paclitaxel micelles has linear PKs.
Conclusion:
In this study, Paclitaxel Micelles was administered safely without premedication for preventing hypersensitivity reactions and showed higher paclitaxel MTD without additional toxicity, which are more advantageous than conventional paclitaxel formulation in clinic treatment. Therefore, the recommended dose for the phase II study is 300 mg/m2.
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PL03 - Presidential Symposium (ID 428)
- Event: WCLC 2016
- Type: Plenary
- Track:
- Presentations: 1
- Moderators:D.P. Carbone, R. Pirker
- Coordinates: 12/06/2016, 08:35 - 10:25, Hall D (Plenary Hall)
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PL03.05 - BRAIN: A Phase Ⅲ Trial Comparing WBI and Chemotherapy with Icotinib in NSCLC with Brain Metastases Harboring EGFR Mutations (CTONG 1201) (Abstract under Embargo until December 6, 7:00 CET) (ID 4570)
09:25 - 09:35 | Author(s): J. Feng
- Abstract
- Presentation
Background:
Non-small cell lung cancer (NSCLC) with brain metastases （M） had a poor prognosis. Whole brain irradiation (WBI) is a standard of care for this critical medical condition. The median survival is only 4-6 months. Small molecule inhibitors of epidermal growth factor receptor (EGFR) including icotinib achieved very successful results in advanced NSCLC with EGFR mutations. There were no prospective randomized clinical trials to explore the efficacy of EGFR tyrosine kinase inhibitors (TKIs) on brain M.
Methods:
Advanced NSCLC with EGFR sensitive mutations and brain M were randomized to WBI plus chemotherapy (chemo) or icotinib. Patients in WBI arm received radiotherapy with 30Gy/3Gy/10 fractions plus concurrent or sequential doublet chemo of 4-6 cycles. Patients in EGFR TKI arm received icotinib 125mg orally tid until disease progression. Icotinib could be continued beyond progression if clinical benefit was observed by the investigator. Crossover to icotinib from WBI could be permitted. Key inclusion criteria were EGFR mutations and radiologically confirmed brain M with at least 3 lesions. The primary endpoint was intracranial progression-free survival (iPFS) by investigator assessments according to RECIST v1.1. The secondary endpoints included objective response rate (ORR), PFS and overall survival (OS). Safety and tolerability were assessed by measuring adverse events （AEs） (CTCAE v4).
Results:
From Dec. 2012 to June 2015, 176 patients from 17 sites were randomized to WBI+Chemo arm (N=91) or icotinib arm (N=85). The baseline clinicopathologic factors were balanced between the two groups. Median age was 58, PS 1 was 87.2%, non-smoker 70.9%, adenocarcinoma 96.8%, symptomatic brain M were 16.5%. Icotinib significantly improved median iPFS compared with WBI+chemo: hazard ratio [HR] 0.56; 95% CI: 0.36-0.90; p=0.014 (10.0 vs 4.8 months). Median PFS was 6.8 vs 3.4 months, (HR 0.44, 95% CI 0.31-0.63, P<0.001). Median OS had no significant difference between the arms (18.0 vs 20.5 months, HR 0.93, 95%CI 0.60-1.44, P=0.734). Intracranial ORR was significantly improved with icotinib than WBI+Chemo (67.1% vs 40.9%; p<0.001); Overall ORR was 55.0% vs 11.1% (P<0.001). Grade ≥3 AEs assessed by the investigators were reported in 8.2% (N=7) of patients treated with icotinib and 26.2% (N=28) treated with WBI+Chemo. Most common causally related AEs in the icotinib arm were increased liver transaminase & rash; in the WBI+Chemo arm were hematologic toxicity.
Conclusion:
Icotinib demonstrated superior iPFS, PFS and ORR over WBI+Chemo in EGFR mutant advanced NSCLC with brain M, and well-tolerated safety profile. Icotinib would be a treatment option for EGFR mutant patients with brain M (NCT01724801).
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