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.

Clinical Institute

Neurosciences (Brain & Spine)

Clinical Institute

Cancer

Specialty/Research Institute

Oncology

Specialty/Research Institute

Neurosciences

Specialty/Research Institute

Pharmacy

DOI

10.1093/noajnl/vdae049