Efficacy and safety of patupilone in non-small cell lung cancer (NSCLC): A phase I/II trial

• DOI: 10.1200/jco.2006.24.18_suppl.7104
• Publication Date: 2020-03-09T19:55:53Z
• Authors: J. M. Sánchez; A. Mellemgaard; M. Perry; P. Zatloukal; J. Hamm; C. P. Belani; E. Kim; E. Felip; M. Berton; A. Johri
• Keywords: 03 medical and health sciences; 0302 clinical medicine; 3. Good health

7104 Background: Based on its activity in a wide range of tumors including those that are taxane resistant, the novel microtubule stabilizer patupilone (EPO906; epothilone B) has the potential to treat NSCLC. Fifty patients were enrolled in phase I to evaluate safety, efficacy, and optimal dose. The phase II part of this study is investigating the antitumor activity of patupilone in 53 patients with stage IIIB/IV NSCLC. Methods: Patients with histologically or cytologically confirmed unresectable, locally advanced, or metastatic NSCLC documented before 1st-line therapy without symptomatic or uncontrolled brain metastases received patupilone at a starting dose of 10.0 mg/m2 q3wk by 20-minute IV infusion. Additional inclusion criteria: age ≥18 years; WHO performance status 0–1; prior treatment with a platinum-containing regimen. Primary objective of the phase II, single-arm, 2-stage, multicenter trial: to determine activity of patupilone q3wk (overall response using modified RECIST) in NSCLC. An additional cohort with recurrent brain metastases from NSCLC is being accrued to evaluate safety, pharmacokinetics, and activity. Results: In phase I, all patients received prior treatment with platinum therapy; 28% had received taxanes and 78% nontaxanes. Patupilone dose was escalated from 6.5 to 13.0 mg/m2 q3wk. Dose-limiting toxicities occurred in 4 patients: 1 with grade 3 asthenia and 3 with grade 3 diarrhea at various dose levels. The most frequent adverse events (AEs) were diarrhea (66%), nausea (40%), vomiting (34%), paraesthesia (32%), abdominal pain (30%), and fatigue (30%). The most frequent grade 3 AE was diarrhea (14%); a grade 4 AE (asthenia) occurred in 1 patient. Overall phase I response: 5 PR, 16 SD, and 26 PD. Based on risk-benefit analyses, 10.0 mg/m2 q3wk was recommended as the phase II dose. Phase II is ongoing: 25 of 53 patients (15 men and 6 women with NSCLC; 2 men and 2 women with brain metastases) have been enrolled. Conclusions: In phase I, patupilone q3wk was safe and well tolerated, with antitumor activity in patients with advanced pretreated NSCLC. Data from phase II will be available at time of presentation. [Table: see text]