Researchers at the Beth Israel Deaconess Medical Center in Boston recently found that Crizotinib was associated with systemic and intracranial disease control in patients with ALK-rearranged non-small lung cancer who had brain metastases. Results from the study titled “Clinical Experience With Crizotinib in Patients With Advanced ALK-Rearranged Non–Small-Cell Lung Cancer and Brain Metastases” were recently published in the Journal of Clinical Oncology.
Researchers found that progression of predating or development of new intracranial lesions while receiving therapy was a common manifestation of acquired resistance to crizotinib.
Crizotinib is an oral kinase inhibitor approved by the US Food and Drug Administration in August 2011 for the treatment of ALK-rearranged non–small-cell lung cancer (NSCLC). However, the efficacy of crizotinib in patients with brain metastases remains unknown.
“Brain metastases are, unfortunately, common in patients with advanced lung cancer” said Daniel B. Costa, MD, PhD, of the division of hematology/oncology at Beth Israel Deaconess Medical Center in a recent news release. “Patients with brain metastases are underrepresented — and sometimes overtly excluded — in clinical trials of novel anti-cancer compounds. Further, most novel oral anti-cancer drugs approved by the FDA for advanced lung cancer — called kinase inhibitors — have low brain penetration due to the blood–brain barrier, which in non-cancerous conditions tries to minimize toxin exposure to the brain, and their effect in brain metastases is understudied.”
To address this clinical unmet issue, Daniel B. Costa, MD, PhD, part of the Division of Hematology/Oncology at Beth Israel Deaconess Medical Center along with colleagues randomly assigned 888 patients with advanced ALK-rearranged NSCLC to two clinical studies designed to test the efficacy of the drug: PROFILE 1005 or 1007.
A total of 166 received prior brain radiotherapy as treatment, while 109 patients did not. The results showed that at baseline, 31% of patients had asymptomatic brain metastases and after 12 weeks systemic disease control rate was of 63% in patients with asymptomatic metastases, and of 65% in patients with treated metastases.
Intracranial disease control rate (DCR) was 56% in patients with asymptomatic metastases and 62% in patients with treated metastases, with a median intracranial time to progression of 7 months and 13.2 months, respectively. After 12 weeks, patients with systemic disease control were likely to experience intracranial disease control. Disease progression was observed in 253 patients without baseline brain metastases of which 20% developed brain metastases with disease progression after 29.9 weeks.
“Our group was able to determine two important findings,” Dr. Costa said in the news release. “Crizotinib has initial adequate activity in brain metastases, with most patients with these lesions having them under control within the initial months of therapy. However, eventual progression or development of brain metastases was common in patients, and highlights that brain metastases will continue to be an unmet clinical need in the management of these patients.”
“The findings may change clinical practice by enforcing that oral anti-cancer inhibitors, such as crizotinib, should not be omitted in patients with brain metastases and by ensuring that future clinical trials both enroll and evaluate brain metastases during the development of novel anti-cancer drugs for lung cancer,” Dr. Costa concluded.