Lazcluze Shows Central Nervous System Activity In EGFR-Variant NSCLC

Lazcluze shows promise as a potential treatment option for patients with EGFR-variant NSCLC, demonstrating significant central nervous system activity in both T790M-positive and -negative cases.

For patients with metastatic EGFR-variant non-small cell lung cancer (NSCLC), Lazcluze (lazertinib) has shown significant activity in the central nervous system (CNS), regardless of T790M status, a genetic marker found in some people with lung cancer. This means it can affect the brain and spinal cord effectively.

Researchers showed that the drug was effective in stopping the growth of cancer that had spread to the brain, with or without spread to the lining of the brain and spinal cord, after unsuccessful treatment with first- or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs; drugs that block the activity of enzymes involved in cell growth).

“These results indicate that in some cases, attempting [Lazcluze] therapy instead of up-front brain local treatment could potentially become a viable treatment option for patients who have experienced failure with first-generation or second- generation EGFR TKIs and developed brain progression,” study authors wrote.

According to study findings published in JAMA Oncology, after a median follow-up of 13.6 months, the intracranial overall response rate (iORR; percentage of patients with brain tumors who respond to treatment) for the evaluable population was 55%. For patients with T790M-positive disease (a type of lung cancer resistant to some treatments), the iORR was 80%, while for patients with T790M-negative disease (no mutation), it was 43%. Patients with T790M-unknown (mutation unknown) disease had an iORR of 67%.

The median intracranial progression-free survival (iPFS; time without cancer in the brain worsening) was 15.8 months for the evaluable population, 15.2 months for the T790M-positive subgroup, 15.4 months for the T790M-negative subgroup, and 18 months for the T790M-unknown subgroup.

Of note, the cerebrospinal fluid penetration rate, or the ability of the drug to pass through the blood-brain barrier and into the cerebrospinal fluid, of Lazcluze was 46.2%, providing further support that the treatment effectively works in the brain.

Side effects were reported in nearly all patients, with treatment-related side effects occurring in 35 of 40 patients. Fifteen patients experienced severe or worse side effects, and four of those cases were related to the treatment. Serious side effects occurred in 15 patients, with five of these cases linked to the treatment. While three patients passed away due to side effects, none of these deaths were related to the treatment. Additionally, three patients stopped taking the treatment because of side effects.

The most common side effects were tingling or numbness, skin rash and itching. Five patients experienced increased liver enzymes and nerve problems. Only a few serious side effects occurred, including diarrhea, fatigue, and lung inflammation, each affecting one patient. Importantly, the most common side effects were generally mild and manageable.

“The safety profile of Lazcluze in this study remained consistent with findings from other previous studies, and no new AEs were identified,” study authors wrote.

Among 40 included patients, 25 were women and the median age was 63 years. A total of 38 patients were evaluable for tumor response, including 12 patients with leptomeningeal metastases (cancer cells that have spread to the membranes around the brain and spinal cord). Half of the enrolled patients had an exon 19 deletion, meaning treatment resistant to EFG TKIs. Regarding T790M status, 12 patients were classified as T790M-unknown, 23 classified as T790M-negative and five classified as T790M-positive disease.

Patients were given Lazcluze, 240 milligrams, once daily regardless of their meals for 42 days.

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