Patupilone for the treatment of recurrent/progressive brain metastases in patients (pts) with non-small cell lung cancer (NSCLC): An open-label phase II study

Abstract

2033 Background: Preclinical data have shown that patupilone, a novel microtubule stabilizer, crosses the intact blood brain barrier in mice, rats and dogs and has antitumor activity in brain tumor models. This study evaluates patupilone's efficacy in NSCLC pts with brain metastases and progression after chemotherapy, surgery and/or radiation to the brain. Methods: This open-label, single-arm, multicenter, phase II, Simon 2-stage (St) study (25 pts per St) uses a multinomial design (response (R), early progression (EP)). Primary efficacy endpoints were a combination of EP (PD or death before cycle 1 Day 21) and R (progression free at 9 wks). Criteria to proceed to St 2 were >3 R and <11 EP in 25 pts. Eligible pts had confirmed NSCLC and ≥1 recurrent, measurable intracranial lesion ≥2 cm. Patupilone was given as 10 mg/m2 in a single 20-min IV infusion every 3 wks. Results: So far, 25 pts in St I and 2 pts in St II (median age 62 yrs, range 40–74, 59% male) have received 78 cycles (median 2 cycles). All pts received prior radiotherapy and 10/27 (37%) had prior chemotherapy for the brain. Karnofsky status in 25/27 ≥70% and in 2/27 <70%. Common G1/2 adverse events (AEs) were as follows: diarrhea 59%, nausea 19%, fatigue and peripheral neuropathy, each 11%. There were 21 G3 AEs (44%); 10 were related to study drug (diarrhea in 6). Eight G4 AEs (19%) were not related and 1 G4 AE (colitis) was suspected. Investigator reported efficacy data from St 1 (n=25) showed 8 responders (median duration of response 192 days, range 191–273); 7 had stable disease, 9 EP and assessment was unknown in 1 pt. Investigator reported median progression free survival is 1.2 mos. Three of the responding patients continued ≥8 cycles. Conclusions: The study met the statistical criteria to proceed to St 2. Proof of concept of patupilone activity in human brain metastases has been reached. These results warrant further investigation of patupilone as a treatment for CNS metastases from NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis Novartis AstraZeneca, Aventis, Eli Lilly, Genentech™ BioOncology, Pfizer Merck, Novartis