Tesetaxel, a novel oral taxane, as second-line therapy for advanced gastroesophageal cancer: Activity in a dose-ranging study.

Abstract

47 Background: Standard taxanes require extended IV infusion and are associated with potentially severe hypersensitivity and cumulative neuropathy. Tesetaxel is a structurally novel orally active taxane with potent and superior antitumor activity relative to standard taxanes in human tumor xenografts that overexpress P-glycoprotein. Tesetaxel is not associated with hypersensitivity, thus eliminating the need for both premedication and extended medical/nursing observation. A prior study showed an overall major response rate (ORR) of 20% as 2nd-line therapy in pts with advanced gastric cancer. Since pharmacokinetic and safety data suggested that flat dosing of tesetaxel might be feasible, we evaluated both flat and weight-based dosing in a new dose-ranging study. Methods: Eligibility: adenocarcinoma (stomach or GE junction); treatment with 1 fluoropyrimidine/platinum analog regimen; ECOG PS 0-1; and adequate organ function. Tesetaxel was administered Q3 weeks at flat starting doses (40 mg and 50 mg) in Cohorts 1 and 2, respectively. When flat dosing proved impractical, a weight-based dose was used for Cohort 3 (27 mg/m2 with escalation to 35 mg mg/m2 pending tolerability). ORR was the primary endpoint. Results: To date, 36 pts (29 men, 7 women; median age, 58 years [range: 25-81]) have been enrolled in this ongoing study, with results as shown below. Median survival is 7.8 and 7.5 months in Cohorts 1 and 2, respectively, and is too early to estimate in Cohort 3. Uncomplicated neutropenia was the most common ≥ 3 event (13%). Conclusions: Extreme body weight differences resulted in marked underdosing and precluded flat dosing. Our data confirm that tesetaxel is active against gastroesophageal cancers in the 2nd-line setting using the weight-based Q3 week regimen. [Table: see text]