In:
Cancer Science, Wiley, Vol. 109, No. 9 ( 2018-09), p. 2852-2862
Abstract:
Epidermal growth factor receptor ( EGFR )‐activating mutations confer sensitivity to tyrosine kinase inhibitor ( TKI ) treatment for non‐small‐cell lung cancer ( NSCLC ). ASP 8273 is a highly specific, irreversible, once‐daily, oral, EGFR TKI that inhibits both activating and resistance mutations. This ASP 8273 dose‐escalation/dose‐expansion study ( NCT 02192697) was undertaken in two phases. In phase I, Japanese patients (aged ≥20 years) with NSCLC previously treated with ≥1 EGFR TKI received escalating ASP 8273 doses (25‐600 mg) to assess safety/tolerability and to determine the maximum tolerated dose ( MTD ) and/or the recommended phase II dose ( RP 2D) by the Bayesian Continual Reassessment Method. In phase II, adult patients with T790M‐positive NSCLC in Japan, Korea, and Taiwan received ASP 8273 at RP 2D to further assess safety/tolerability and determine antitumor activity, which was evaluated according to Simon's two‐stage design (threshold response = 30%, expected response = 50%, α = 0.05, β = 0.1). Overall, 121 (n = 45 [33W/12M] phase I, n = 76 [48W/28M] ) phase 2) patients received ≥1 dose of ASP 8273. In phase I, RP 2D and MTD were established as 300 and 400 mg, respectively. As 27 of the 63 patients treated with ASP 8273 300 mg achieved a clinical response, ASP 8273 was determined to have antitumor activity. The overall response rate at week 24 in all patients was 42% (n = 32/76; 95% confidence interval, 30.9‐54.0). Median duration of progression‐free survival was 8.1 months (95% confidence interval, 5.6, upper bound not reached). The most commonly reported treatment‐related adverse event in phase II was diarrhea (57%, n = 43/76). ASP 8273 300 mg was generally well tolerated and showed antitumor activity in Asian patients with both EGFR ‐activating and T790M mutations.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2018.109.issue-9
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
Permalink