Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer

Lakshmi Nayak, Lisa M. Deangelis, H. Ian Robins, Ramaswamy Govindan, Shirish Gadgeel, Karen Kelly, James R. Rigas, David M. Peereboom, Steven Rosenfeld, Alona Muzikansky, Ming Zheng, Patrick Urban, Lauren E. Abrey, Antonio Omuro, Patrick Y. Wen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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/m2 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/m2. 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.

Original languageEnglish (US)
Pages (from-to)4165-4172
Number of pages8
JournalCancer
Volume121
Issue number23
DOIs
StatePublished - Dec 1 2015
Externally publishedYes

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Non-Small Cell Lung Carcinoma
Neoplasm Metastasis
Brain
Brain Neoplasms
Disease-Free Survival
Pharmacokinetics
Pharmaceutical Preparations
Cytotoxins
Peripheral Nervous System Diseases
Blood-Brain Barrier
Pulmonary Embolism
Microtubules
Disease Progression
epothilone B
Diarrhea
Seizures
Prospective Studies
Safety
Drug Therapy
Survival

Keywords

  • brain metastases
  • chemotherapy
  • non-small cell lung cancer
  • patupilone
  • recurrent metastases

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Nayak, L., Deangelis, L. M., Robins, H. I., Govindan, R., Gadgeel, S., Kelly, K., ... Wen, P. Y. (2015). Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer. Cancer, 121(23), 4165-4172. https://doi.org/10.1002/cncr.29636

Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer. / Nayak, Lakshmi; Deangelis, Lisa M.; Robins, H. Ian; Govindan, Ramaswamy; Gadgeel, Shirish; Kelly, Karen; Rigas, James R.; Peereboom, David M.; Rosenfeld, Steven; Muzikansky, Alona; Zheng, Ming; Urban, Patrick; Abrey, Lauren E.; Omuro, Antonio; Wen, Patrick Y.

In: Cancer, Vol. 121, No. 23, 01.12.2015, p. 4165-4172.

Research output: Contribution to journalArticle

Nayak, L, Deangelis, LM, Robins, HI, Govindan, R, Gadgeel, S, Kelly, K, Rigas, JR, Peereboom, DM, Rosenfeld, S, Muzikansky, A, Zheng, M, Urban, P, Abrey, LE, Omuro, A & Wen, PY 2015, 'Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer', Cancer, vol. 121, no. 23, pp. 4165-4172. https://doi.org/10.1002/cncr.29636
Nayak L, Deangelis LM, Robins HI, Govindan R, Gadgeel S, Kelly K et al. Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer. Cancer. 2015 Dec 1;121(23):4165-4172. https://doi.org/10.1002/cncr.29636
Nayak, Lakshmi ; Deangelis, Lisa M. ; Robins, H. Ian ; Govindan, Ramaswamy ; Gadgeel, Shirish ; Kelly, Karen ; Rigas, James R. ; Peereboom, David M. ; Rosenfeld, Steven ; Muzikansky, Alona ; Zheng, Ming ; Urban, Patrick ; Abrey, Lauren E. ; Omuro, Antonio ; Wen, Patrick Y. / Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer. In: Cancer. 2015 ; Vol. 121, No. 23. pp. 4165-4172.
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abstract = "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/m2 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/m2. 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.",
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T1 - Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer

AU - Nayak, Lakshmi

AU - Deangelis, Lisa M.

AU - Robins, H. Ian

AU - Govindan, Ramaswamy

AU - Gadgeel, Shirish

AU - Kelly, Karen

AU - Rigas, James R.

AU - Peereboom, David M.

AU - Rosenfeld, Steven

AU - Muzikansky, Alona

AU - Zheng, Ming

AU - Urban, Patrick

AU - Abrey, Lauren E.

AU - Omuro, Antonio

AU - Wen, Patrick Y.

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N2 - 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/m2 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/m2. 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.

AB - 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/m2 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/m2. 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.

KW - brain metastases

KW - chemotherapy

KW - non-small cell lung cancer

KW - patupilone

KW - recurrent metastases

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