AstraZeneca’s Therapy Aids Lung Cancer Patients with Rare Complication

AstraZeneca’s Therapy Aids Lung Cancer Patients with Rare Complication

Results from the Phase I BLOOM clinical trial revealed that AstraZeneca’s AZD9291 offer encouraging activity in heavily pretreated non-small cell lung cancer (NSCLC) patients with leptomeningeal disease.

The data was presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Nov. 5–9 in Boston, Massachusetts.

NSCLC patients with leptomeningeal disease suffer from a rare complication in which the cancer spreads to layers of tissue that protect the brain and spinal cord. It is estimated that up to 15% of patients develop this complication as lung cancer progresses. Furthermore, an elevated risk of central nervous system (CNS) involvement was noticed among patients with NSCLC due to a mutation in the EGFR receptor, especially among those treated with the inhibitor EGFR-TKI.

From a therapeutic perspective, there is no effective treatment currently available for leptomeningeal disease. However, preclinical studies and anecdotal patient accounts suggested that AZD9291 (epidermal growth factor receptor-tyrosine kinase inhibitor, abbreviated as EGFR-TKI) was able to pass the blood-brain barrier (the barrier that frequently prevents drugs from reaching the brain) to act against brain tumors with EGFR mutations. Based on these findings, the antitumor efficacy and safety of AZD9291 was tested in NSCLC patients with leptomeningeal disease or brain metastases.

A total of 13 heavily pretreated NSCLC patients were enrolled in this Phase I clinical trial. Prior therapies for these patients include EGFR-TKIs drug in 10 patients and radiotherapy to the brain in seven patients. AZD9291 at 160mg was administrated to the patients once a day until disease progression, at which point treatment continued at the investigator’s discretion. Among the patients, 11 were examined for response using mainly brain MRI imaging.

“There is no standardized way to measure response of leptomeningeal disease to therapy, but a combination of clearing cancer cells from the fluid surrounding the brain (CSF cytology), changes on brain MRI imaging, and improvement in neurologic symptoms is likely to be the best composite endpoint to assess clinical benefit,” said Dae Ho Lee, MD, PhD, associate professor in the Department of Oncology in the University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

The results suggested improvement observed in brain imaging in six patients, and three out of seven patients with previous abnormal neurological exams displayed improvement. Clearance of cancer cells from the CSF was proved in one patient, but unconfirmed in four other patients. Also, available pre- and post-treatment CSF samples showed significant reduction in DNA mutation of EGFR receptor in eight out of nine patients, with the reduction exceeding 50% in five patients.

Overall, these preliminary results highlight the promising activity of AZD9291 in NSCLC patients with leptomeningeal disease. In the future, the researchers suggest that a longer follow-up is required to gain better understanding of AZD9291 in CNS disease-associated NSCLC with mutation in EGFR receptor.

“Our results show that AZD9291 is a well-tolerated compound in this difficult-to-treat setting, and demonstrated that it crosses the blood-brain barrier. Although preliminary, these results show encouraging activity and a manageable safety profile in a patient population with few treatment options. The results support further investigation of AZD9291 in central nervous system disease,” Dr. Lee added.

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