Phase I/II study of ABI-007 as first line chemotherapy in advanced non-small cell lung cancer (NSCLC)

Abstract

7105 Background: ABI-007 is a 130-nm albumin-bound form of paclitaxel. This study was designed to determine (1) the MTD and DLTs of ABI-007 in patients with stage IV chemotherapy-naive NSCLC and (2) the efficacy and safety of ABI-007 at the MTD. Methods: Eligibility requirement included ECOG PS 0–1, adequate organ function and sensory neuropathy ≤ grade 1. No prior chemotherapy for metastatic disease was allowed. Prior EGFR TKI therapy was allowed. ABI-007 was administered on days 1, 8, and 15 every 28 days (IV over 30 min. without premedication). In the phase I portion, 3 dose levels were studied (100, 125 and 150 mg/m 2 ) and in the phase 2 portion, 40 patients were treated at the MTD. Results: 50 patients received ABI-007; the median age was 70 yo and 76% of patients were ≥ 65 yo. No DLTs were observed at the 100 and 125 mg/m 2 dose level. However at the 150 mg/m 2 dose level 2/6 patients had a DLT (febrile neutropenia and sensory neuropathy, respectively) during cycle 1 such that the MTD was exceeded. The 125 mg/m 2 dose level was identified as the MTD and expanded to 40 patients in the phase 2 portion of this study. Toxicity and efficacy data is presented for the phase 2 portion. Ten patients (25%) had received prior neoadjuvant or adjuvant chemotherapy and 5 (13%) had received prior gefitinib or erlotinib. Sensory neuropathy was the most frequent toxicity with grade 2 and 3 toxicity occurring in 8% and 15% of patients. Grade 2 and 3 fatigue was observed in 8% and 13% of patients. Grade 3 and 4 neutropenia occurred in 10% and 3% of patients with no febrile neutropenia observed. Response was assessed by RECIST. One CR and 14 PRs were observed for an overall response rate of 15/40 (38%). The median survival was 10.3 months. Conclusions: The MTD for ABI-007 administered over 30 min. on days 1, 8, and 15 every 28 days was 125 mg/m 2 . No hypersensitivity reactions were observed and no premedication was given. In the phase 2 portion, a 38% response rate and 10.3 month survival was observed. Non-hematologic toxicities were primarily sensory neuropathy and fatigue. Myelosuppression was minimal and no febrile neutropenia was observed. Further development of ABI-007 in NSCLC is warranted based on the encouraging single agent activity observed in this study. [Table: see text]