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J. Ni
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-005 - Relationship between Icotinib Exposure and Clinical Outcome in Chinese ANSCLC (ID 370)
09:30 - 09:30 | Author(s): J. Ni
- Abstract
Background:
The icotinib hydrochloride tablets (Conmana) is a novel orally administered EGFR-TKI agent, which is the first homegrown anticancer drug designed, synthesizedand screened by Betapharma (Zhejiang, China) . The preclinical animal experiments showed that the agent had an anticancer activity in vitro and in vivo whose mechanism is that icotinib can inhibit EGFR activity specifically and competitively through binding to the tyrosine of the EGFR. A head-to-head Phase III clinical trial (ICOGEN) comparing the roles of icotinib and gefitinib in treating NSCLC in China has suggested that icotinib has similar (and even better) efficacy with gefitinib in treating Chinese NSCLC patients, with much better safety profiles; furthermore, it is superior to gefitinib in terms of treatment cost. Recently, a retrospective study demostrated that icotinib is active in the treatment of patients with NSCLC both in first or second/third line. Up to date, Icotinib has completed phase I、 II and III trials, Pharmacokinetic study in Phase I clinical trial data displayde that non-linear character with saturated absorption and first-order elimination. But whether the exposure of icotinib would influence the therapeutic effects is cofused us.So Beta Pharma (China) and Peking Union Medical College Hospital (PUMCH) jointly conducted this single-center open-label Phase I clinical trial, from August 2007 to April 2009, to explore the relationship between icotinib exposure and clinical outcomes of a single dose or administration for 31 consecutive days among Chinese NSCLC patients. In this article, by analysing the clinical efficacies and pharmacokinetic characteristics of iconitib in 30 subjects, we tried to elucidate the relationship between the iconitib exposure and therapeutic effects.
Methods:
In this single-center open-label phase I clinical trial, a dose-escalation method was applied until disease progression or unacceptable toxicities. Different doses of icotinib were orally administered for 31 consecutive days in different groups until disease progression or unacceptable toxicities. Blood samples were collected in the first treatment cycle (day 1 - day 28) for the pharmacokinetic analysis. Tumor responses were assessed by using the Response Evaluation Criteria in Solid Tumors(RECIST). The plasma concentrations of icotinib were assessed by liquid chromatography–mass spectrometry (LC-MS).
Results:
Univariate analysis showed that the time to maximum (Tmax) after a single dose of icotinib was significantly correlated with the overall survival (OS) (Spearman correlation coefficient=0.441, P=0.021). Patients with higher Clast were independently associated with PFS (p=0.012). Multivariate analysis showed that the AUC0-last and AUC0-∞ after a single dose of icotinib were significantly correlated with OS (P=0.037, P=0.042, respectively).. Stratification of these subjects according to smoking status indicated significant correlation between OS and AUC0-last (Spearman correlation coefficient = -0.709, P=0.015).
Conclusion:
Iconitib is a novel EGFR TKI developed by Chinese scientists. For advanced NSCLC patients who have failed prior treatment(s), the exposure of a single dose of iconitib was significantly correlated with the treatment efficacy. This finding may provide a simple and feasible clinical indicator for predicting the survivals.
