Temodar Plus Tyrosine Kinase Inhibitors for Progressive CNS Disease

Temozolomide is an oral alkylating chemotherapy which has good CNS penetration and has demonstrated CNS responses in both primary brain tumors (e.g., glioblastoma and anaplastic astrocytoma) and in small cell lung cancer (SCLC) brain metastases. Preclinical data from glioblastoma suggests potential synergy of concurrent ALK or EGFR inhibition with temozolomide and early phase trials in glioblastoma are ongoing investigating such combinations. It is felt that combining temozolomide with osimertinib or lorlatinib may be beneficial for patients with progressive CNS disease on either of these TKIs because of the high CNS penetration of temozolomide, good CNS activity of temozolomide in other tumor types and preclinical data from glioblastoma suggesting a potential enhanced effect of concurrent EGFR and ALK/ROS1 inhibition with temozolomide.

Temozolomide is an oral alkylating chemotherapy which has good CNS penetration and has demonstrated CNS responses in both primary brain tumors (e.g., glioblastoma and anaplastic astrocytoma) and in small cell lung cancer (SCLC) brain metastases. Preclinical data from glioblastoma suggests potential synergy of concurrent ALK or EGFR inhibition with temozolomide and early phase trials in glioblastoma are ongoing investigating such combinations. It is felt that combining temozolomide with osimertinib or lorlatinib may be beneficial for patients with progressive CNS disease on either of these TKIs because of the high CNS penetration of temozolomide, good CNS activity of temozolomide in other tumor types and preclinical data from glioblastoma suggesting a potential enhanced effect of concurrent EGFR and ALK/ROS1 inhibition with temozolomide