A phase I dose-escalation study of pulsatile afatinib in patients with recurrent or progressive brain cancer.

Publication Title

Neurooncol Adv

Authors

• Tiffany Juarez, Department of Translational Neurosciences and Neurotherapeutics, Pacific Neuroscience Institute, John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.Follow
• Jaya Mini Gill, Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neuro-Oncology, Santa Monica, California, USA.Follow
• Annie Heng, Department of Translational Neurosciences and Neurotherapeutics, Pacific Neuroscience Institute, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USAFollow
• Jose Carrillo, Pacific Neuroscience Institute, Santa Monica, California, USA; Department of Translational Neurosciences, Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USAFollow
• Naveed Wagle, Pacific Neuroscience Institute, Santa Monica, California, USA; Department of Translational Neurosciences, Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USAFollow
• Natsuko Nomura, John Wayne Cancer Institute and Pacific Neuroscience Institute at Providence Saint John's Health Center, Santa Monica, CA, USA.Follow
• Minhdan Nguyen, Department of Translational Neurosciences and Neurotherapeutics, Pacific Neuroscience Institute, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USAFollow
• Judy D Truong, Department of Translational Neurosciences and Neurotherapeutics, Pacific Neuroscience Institute, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USAFollow
• Lucia Dobrawa, Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neuro-Oncology, Santa Monica, California, USA.Follow
• Walavan Sivakumar, Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neuro-Oncology, Santa Monica, California, USA.Follow
• Garni Barkhoudarian, Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neuro-Oncology, Santa Monica, California, USA.Follow
• Daniel F Kelly, Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neuro-Oncology, Santa Monica, California, USA.Follow
• Santosh Kesari, Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute/Pacific Neuroscience Institute, 2200 Santa Monica Boulevard, Santa Monica, CA, 90404, USAFollow

Document Type

Article

Publication Date

1-1-2024

Keywords

california; santa monica; sjci; pacific neurosciences

Abstract

BACKGROUND: Afatinib (BIBW2992; Gilotrif®) is a selective and irreversible inhibitor of the epidermal growth factor receptor (ErbB; EGFR) family. It inhibits EGFR, HER2, and HER4 phosphorylation, resulting in tumor growth inhibition and regression. This phase I dose-escalation trial of pulsatile afatinib examined the safety, drug penetration into the central nervous system, preliminary antitumor activity, and recommended phase II dose in patients with progressive or recurrent brain cancers.

METHODS: Afatinib was taken orally once every 4 days or once every 7 days depending on dose cohort, until disease progression or unacceptable toxicity.

RESULTS: A total of 24 patients received the investigational agent and were evaluable for safety analyses, and 21 patients were evaluable for efficacy. Dosing was administered at 80 mg every 4 days, 120 mg every 4 days, 180 mg every 4 days, or 280 mg every 7 days. A recommended phase II dose of pulsatile afatinib was established at 280 mg every 7 days as there were no dose-limiting toxicities in any of the dosing cohorts and all toxicities were deemed manageable. The most common drug-related toxicities were diarrhea, rash, nausea, vomiting, fatigue, stomatitis, pruritus, and limb edema. Out of the 21 patients evaluable for efficacy, 2 patients (9.5%) exhibited partial response based on Response Assessment in Neuro-Oncology criteria and disease stabilization was seen in 3 patients (14.3%).

CONCLUSIONS: Afatinib taken orally was safe and well-tolerated up to 280 mg every 7 days in brain cancer patients.

Area of Special Interest

Neurosciences (Brain & Spine)

Area of Special Interest

Cancer

Specialty/Research Institute

Oncology

Specialty/Research Institute

Neurosciences

Specialty/Research Institute

Pharmacy

DOI

10.1093/noajnl/vdae049