Review Note

Discuss systemic therapies which may be useful for treating brain metastases in non-small cell lung cancer. (4 marks) 

· TKI’s: commonly used TKI’s for patients with driver mutations have reasonably strong intracranial penetrance. They are often favoured over surgery/RT in the initial management of asymptomatic intracranial metastases, both due to their relative efficacy due to this penetrance, and because the favourable prognosis they confer results in greater period over which RT toxicities (such as neurocognitive changes from WBRT) can manifest. Examples of mutations and agents used in this setting include: 

o        ALK mutation: alectinib 

o        ROS1 mutation: entrectinib 

o        EGFR mutation: osimertinib  

· Immunotherapy: including agents such as pembrolizumab, commonly given as single agent or in combination with cytotoxic chemotherapy. Studies suggest some intracranial penetrance however evidence not as robust as for TKI’s. Therefore can sometimes be used in setting of small asymptomatic intracranial metastases, however local therapies more commonly used. This decision is partly based on degree of PDL1 expression, with higher levels suggestive of better intracranial response. 

· Cytotoxic chemotherapy: relatively low intracranial penetrance, although combining platinum compounds and third-generation agents are better than with earlier regimens. Generally only confer minimal improvement, with local therapy often required.