Brigatinib, identified by its Chemical Abstracts Service (CAS) number 1197953-54-0, represents a significant advancement in the targeted therapy landscape for certain types of cancer. This potent small-molecule drug is primarily utilized in the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC), a particularly aggressive form of lung cancer.

As a highly selective next-generation tyrosine kinase inhibitor (TKI), Brigatinib operates by targeting the ALK molecular alterations that drive cancer cell growth and survival. The ALK protein, which is generally not expressed in normal adult tissues, becomes a crucial driver in certain NSCLC cases due to chromosomal rearrangements. By inhibiting the abnormal activity of the ALK protein, Brigatinib disrupts these signaling pathways, leading to the reduction in size and number of cancer cells and thereby slowing or stopping disease progression. Furthermore, research suggests that Brigatinib can also inhibit mutated epidermal growth factor receptor (EGFR), and it has demonstrated a remarkable effect on the central nervous system, which is critical given the high incidence of brain metastases in ALK-positive NSCLC patients.

Clinical trials, such as the pivotal ALTA 1L study, have underscored Brigatinib's superior efficacy. In head-to-head comparisons, Brigatinib significantly reduced the risk of disease progression or death compared to previous standard therapies, exhibiting a median progression-free survival (PFS) of 24 months, which is more than double that of comparators. The overall tumor response rate (ORR) observed with Brigatinib was robust, with approximately 74% of patients experiencing tumor shrinkage. Importantly, for patients with measurable brain metastases at baseline, Brigatinib showed exceptional intracranial efficacy, with an impressive overall response rate in the brain, suggesting its ability to effectively penetrate the central nervous system and control disease spread to this critical area. This translates to prolonged intracranial progression-free survival and improved quality of life for many patients, allowing them to maintain active lifestyles.

Brigatinib is typically administered orally once daily, often beginning with a lower introductory dose before escalating to a higher therapeutic dose, a regimen designed to optimize patient tolerability. Regular monitoring through blood tests is essential to assess various bodily functions, including liver and kidney health, blood cell counts, and metabolic markers. While generally well-tolerated, like all targeted therapies, Brigatinib may be associated with certain side effects. Common adverse reactions can include diarrhea, fatigue, nausea, rash, cough, and muscle pain. More serious, though less frequent, side effects requiring close medical attention may involve lung problems such as interstitial lung disease (ILD), elevated blood pressure (hypertension), slow heart rate (bradycardia), vision disturbances, and changes in pancreatic enzyme or blood sugar levels. Patients are advised to promptly report any new or worsening symptoms to their healthcare providers for timely management.

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