Abstract Details

Title An Open-Label, Multi-Center, Phase II Study of Patupilone (EPO906), in the Treatment of Recurrent or Progressive Brain Metastases in Patients with Non-Small Cell Lung Cancer (NSCLC)

Topic Neuro-oncology

Presentation(s) IN10 - (-)

Poster/Presentation
Number 005

Objective

Background There are limited chemotherapy options for NSCLC patients with progressive brain metastases. Patupilone is a microtubule targeting cytotoxic agent, known to cross the blood-brain barrier with activity in a phase I/II study of NSCLC patients.

Design/Methods NSCLC patients, ?18 years and KPS ?50, with radiographically-proven brain metastases that had progressed after chemotherapy, surgery and/or radiation were eligible. Patients with extracranial metastases in >3 organ sites including the primary tumor were excluded. Patients received patupilone at a dose of 10mg/m2 intravenously every 3 weeks. A multinomial 2-stage design was used. The primary endpoint was a combination of early progression rate (progression or death within cycle 1 [EPR]), and response rate (progression-free for 3 cycles [RR]). The drug would be considered active if EPR ?40% and RR ?20% (alpha=10%, power 85%).

Results Fifty patients were enrolled; 25 in each stage. Median age was 60 years (range, 33-74), 42% were women. Forty-nine (98%) patients had received prior radiation, 22 (44%) surgery, and 16 (32%) chemotherapy for brain metastases. Median number of cycles delivered was 2 (range 1-13). RR was 36% (95% CI 20-50%), and EPR 26% (95% CI: 10-40%). Mean AUC(0-tau) for Cycles 1 and 3 were 1544 and 1978 ng.h/mL, respectively, and mean steady state volume of distribution was 755 L/m2. The most frequent grade 3-4 adverse events (AE) were diarrhea (24%), hypokalemia (8%), pulmonary embolism (8%), peripheral neuropathy (4%), sepsis (4%), and neutropenia (4%). Grades 1-3 peripheral neuropathy was seen in 38% of patients. All patients discontinued the study drug; 31 (62%) for disease progression, 13 (26%) for AE, 6 (12%) for other reasons (eg.consent withdrawn). Thirty-two deaths occurred; 25 from brain metastases.

Conclusions Patupilone has activity in NSCLC with brain metastases with a manageable side-effect profile.

Authors/Disclosures
Lakshmi Nayak, MD (Dana Farber Cancer Institute, Center for Neuro-oncology) PRESENTER	Dr. Nayak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono Pharmaceutical. An immediate family member of Dr. Nayak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BraveBio. Dr. Nayak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kite/Gilead. Dr. Nayak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genmab. Dr. Nayak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Curis. Dr. Nayak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Miltenyi. Dr. Nayak has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Ono. Dr. Nayak has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Astra Zeneca. Dr. Nayak has received publishing royalties from a publication relating to health care.
Lauren E. Abrey, MD	No disclosure on file
Lisa M. DeAngelis, MD, FAAN (Memorial Sloan-Kettering Cancer Center)	Dr. DeAngelis has received publishing royalties from a publication relating to health care.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
John T. Kissel, MD, FAAN	Dr. Kissel has nothing to disclose.
Antonio M. Omuro, MD, FAAN (Stanford University)	Dr. Omuro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono Therapeutics. Dr. Omuro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Telix. Dr. Omuro has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Curevac. The institution of Dr. Omuro has received research support from NIH. The institution of Dr. Omuro has received research support from Arcus Biosciences. The institution of Dr. Omuro has received research support from Denovo Biopharma. The institution of Dr. Omuro has received research support from Ono Pharmaceutical. The institution of Dr. Omuro has received research support from Servier. The institution of Dr. Omuro has received research support from Nanopharmaceuticals. The institution of Dr. Omuro has received research support from Denovo.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Steven S. Rosenfeld, MD, PhD (The Neurological Institute of New York)	No disclosure on file
Patrick Y. Wen, MD, FAAN (Dana-Farber/Brigham and Women'S Cancer Center)	Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra Zeneca . Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Black Diamond . Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celularity. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Chimerix. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Day One Bio . Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genenta. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Glaxo Smith Kline . Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mundipharma. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis . Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nuvation Bio . Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novocure. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prelude Therapeutics . Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sagimet. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sapience. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Servier. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vascular Biogenics . Dr. Wen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for VBI Vaccines . Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Astra Zeneca . Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Black Diamond . Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celularity. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chimerix. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Day One Bio . Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genenta. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Glaxo Smith Kline . Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Mundipharma. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Nuvation Bio. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novocure. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Prelude Therapeutics. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sagimet. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sapience. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Servier. Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vascular Biogenics . Dr. Wen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for VBI Vaccines . Dr. Wen has received research support from Astra Zeneca . Dr. Wen has received research support from Black Diamond . Dr. Wen has received research support from Bristol Meyers Squibb . Dr. Wen has received research support from Celgene. Dr. Wen has received research support from Chimerix. Dr. Wen has received research support from Eli Lily . Dr. Wen has received research support from Erasca. Dr. Wen has received research support from Genentech/Roche . Dr. Wen has received research support from Kazia . Dr. Wen has received research support from MediciNova. Dr. Wen has received research support from Merck. Dr. Wen has received research support from Novartis. Dr. Wen has received research support from Nuvation Bio . Dr. Wen has received research support from Servier. Dr. Wen has received research support from Vascular Biogenics . Dr. Wen has received research support from VBI Vaccines . Dr. Wen has received publishing royalties from a publication relating to health care.

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