What is the effect of dacomitinib on entering the brain and controlling bone metastasis?

Dacomitinib has strong blood-brain barrier penetration, so it has outstanding performance in treating brain metastases from lung cancer and can delay the progression of brain metastases. At the same time, dacomitinib also has a certain control effect on bone metastasis, but it needs to be combined with other treatments such as local radiotherapy as directed by the doctor.

Dacomitinib drug overview

is a second-generation EGFR tyrosine kinase inhibitor (TKI) that irreversibly binds and inhibits EGFR/Her1, Her2 and Her4 subtypes, and its efficacy is comparable to other TKIs.

In the ARCHER1050 trial, dacomitinib improved progression-free survival compared with gefitinib, supporting dacomitinib as a first-line treatment option for advanced non-small cell lung cancer with sensitive EGFR mutations.

Regarding the higher incidence of adverse events, dose reduction will not reduce the efficacy of dacomitinib and can effectively reduce the incidence and severity of adverse events.

Dacomitinib can penetrate the blood-brain barrier

Dacomitinib has a certain ability to penetrate the blood-brain barrier, which is particularly meaningful for the treatment of non-small cell lung cancer patients with central nervous system metastasis. Studies have shown that dacomitinib can cross the blood-brain barrier and reach a certain concentration in brain tissue. It can achieve a certain therapeutic effect on brain metastases in lung cancer patients carrying specific EGFR mutations.

The brain penetration effect of dacomitinib

About 20% of patients with non-small cell lung cancer are diagnosed with brain metastases, which is associated with poor survival outcomes. The ability of tyrosine kinase inhibitor drugs to penetrate the blood-brain barrier makes them potential options for intracranial metastasis. Dacomitinib is an irreversible second-generation pan-HER tyrosine kinase inhibitor that has become the standard therapy for patients with epidermal growth factor receptor mutations. However, its efficacy in patients with brain metastases has not been established.

Patient attention: Case 1 is a 47-year-old man who was admitted to the hospital due to repeated cough and sputum production for more than a year. Computed tomography of the chest revealed a high-density shadow in the left upper lobe. Brain magnetic resonance imaging showed abnormal nodular enhancement of the right cerebellar hemisphere. Case 2 is a 55-year-old man who complained of intermittent cough and sputum production for more than 1 month. Computed tomography of the chest revealed a hyperdense mass in the left upper lobe. Magnetic resonance imaging of the central nervous system showed 2 abnormal nodular enhancements in the left frontal lobe.

Diagnosis: Both patients were diagnosed with lung adenocarcinoma through bronchoscopy and lymph node biopsy.

Interventions: The two patients received dacomitinib 30 mg once daily as first-line therapy for 8 and 11 months, respectively, until disease progression.

Results: After treatment with dacomitinib, both patients achieved complete remission in BMs. Progression-free survival was 11 months and 8 months respectively.

The effect of dacomitinib in the treatment of bone metastasis

Theoretically, dacomitinib, as an EGFR inhibitor, can prevent the proliferation and spread of tumor cells. For lung cancer patients with EGFR mutations, even if bone metastasis occurs, dacomitinib is expected to inhibit the growth of bone metastases by blocking tumor cell signaling pathways. However, the treatment of bone metastases usually requires a combination of local radiotherapy, bone-modifying drugs (such as bisphosphonates), and other systemic treatments, and the efficacy varies from person to person.

Survival period of NSCLC treated with dacomitinib

Dacomitinib is an irreversible pan-HER TKI that targets the EGFR, ErbB2 and ErbB4 kinase domains of the EGFR signaling pathway. As an irreversible inhibitor, dacomitinib has a longer duration of efficacy compared with first-generation TKIs, which were considered an alternative first-line therapy for EGFR-mutant NSCLC in the ARCHER 1050 trial.

In addition, subgroup analysis of exon 21 L858R mutations showed that the median overall survival of patients treated with dacomitinib was 32.5 months, while the median overall survival of patients treated with gefitinib was 23.2 months.

Summary

In short, dacomitinib has outstanding performance in the treatment of brain metastases from lung cancer, while its role in controlling bone metastases needs to be evaluated based on the patient's specific condition and comprehensive treatment plan.

It is recommended that patients strictly follow the doctor's instructions for treatment, and decide the dacomitinib treatment plan based on their own genetic test results, disease stage, physical condition, etc. under the guidance of the doctor.

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