Zipalertinib's Efficacy in EGFR ex20ins NSCLC With Brain Mets
Helena Yu, MD, discusses the efficacy of zipalertinib for EGFR-mutant non–small cell lung cancer and the importance of exploring therapies with CNS penetration in this space.
In an interview with Targeted OncologyTM, Helena Yu, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, discusses zipalertinib and its efficacy for the treamtent of non–small cell lung cancer, especially in patients experiencing brain metastases.
Zipalertinib, an irreversible epidermal growth factor receptor (EGFR) inhibitor, demonstrated clinically meaningful efficacy and a manageable safety profile in pretreated patients with NSCLC harboring EGFRexon 20 insertion (ex20ins) mutations. Data from the phase I/II REZILIENT1 trial (NCT04036682) showed an overall objective response rate (ORR) of 35.2% and a median duration of response (DOR) of 8.8 months in this challenging patient population, which included those previously treated with platinum-based chemotherapy and even other ex20ins-targeted therapies like amivantamab (Rybrevant).
Significantly, zipalertinib also exhibited promising activity against brain metastases, with an ORR of 30.9% in patients with central nervous system (CNS) involvement. Brain metastases represent a critical and frequent complication of NSCLC, affecting a substantial portion of patients, with up to 40% developing them during their disease course. These metastases can lead to severe neurological symptoms such as headaches, seizures, cognitive impairment, and motor deficits, profoundly impacting a patient's quality of life.
Treating NSCLC brain metastases is complex, often requiring a multifaceted approach including radiation therapy (like stereotactic radiosurgery or whole-brain radiation therapy) and sometimes surgery. A primary hurdle has been the blood-brain barrier, which historically limited the effectiveness of many systemic anti-cancer drugs in reaching brain tumors.
The demonstrated efficacy of zipalertinib in patients with CNS metastases is highly impactful. This underscores the increasing importance of targeted therapies, such as zipalertinib for EGFR ex20ins mutations, which are designed to effectively penetrate the blood-brain barrier. Such systemic agents offer a crucial advantage by addressing both intracranial and extracranial disease, potentially leading to more comprehensive and durable responses. This provides a vital systemic treatment option for patients battling this challenging complication, potentially improving their prognosis and overall well-being.
