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Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non–small cell lung cancer
Author(s) -
Nayak Lakshmi,
DeAngelis Lisa M.,
Robins H. Ian,
Govindan Ramaswamy,
Gadgeel Shirish,
Kelly Karen,
Rigas James R.,
Peereboom David M.,
Rosenfeld Steven S.,
Muzikansky Alona,
Zheng Ming,
Urban Patrick,
Abrey Lauren E.,
Omuro Antonio,
Wen Patrick Y.
Publication year - 2015
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.29636
Subject(s) - medicine , lung cancer , brain metastasis , pharmacokinetics , phases of clinical research , clinical endpoint , adverse effect , progression free survival , cancer , urology , oncology , gastroenterology , chemotherapy , metastasis , clinical trial
BACKGROUND Treatment options for patients with non–small cell lung cancer (NSCLC) with brain metastases are limited. Patupilone (EPO906), a blood‐brain barrier–penetrating, microtubule‐targeting, cytotoxic agent, has shown clinical activity in phase 1/2 studies in patients with NSCLC. This study evaluates the efficacy, pharmacokinetics, and safety of patupilone in NSCLC brain metastases. METHODS Adult patients with NSCLC and confirmed progressive brain metastases received patupilone intravenously at 10 mg/m 2 every 3 weeks. The primary endpoint of this multinomial 2‐stage study combined early progression (EP; death or progression within 3 weeks) and progression‐free survival at 9 weeks (PFS9w) to determine drug activity. RESULTS Fifty patients with a median age of 60 years (range, 33‐74 years) were enrolled; the majority were men (58%), and most had received prior therapy for brain metastases (98%). The PFS9w rate was 36%, and the EP rate was 26%. Patupilone blood pharmacokinetic analyses showed mean areas under the concentration‐time curve from time zero to 504 hours for cycles 1 and 3 of 1544 and 1978 ng h/mL, respectively, and a mean steady state distribution volume of 755 L/m 2 . Grade 3/4 adverse events (AEs), regardless of their relation with the study drug, included diarrhea (24%), pulmonary embolisms (8%), convulsions (4%), and peripheral neuropathy (4%). All patients discontinued the study drug: 31 (62%) for disease progression and 13 (26%) for AEs. Twenty‐five of 32 deaths were due to brain metastases. The median time to progression and the overall survival were 3.2 and 8.8 months, respectively. CONCLUSIONS This is the first prospective study of chemotherapy for recurrent brain metastases from NSCLC. In this population, patupilone demonstrated activity in heavily treated patients. Cancer 2015;121:4165–4172. © 2015 American Cancer Society .