ALUNBRIG

ALUNBRIG is a medication prescribed for adults with non-small cell lung cancer (NSCLC) that has a specific abnormal anaplastic lymphoma kinase (ALK) gene and has metastasized to other areas of the body.

Alunbrig is a medication that contains brigatinib as its active drug. It falls under the category of anaplastic lymphoma kinase (ALK) inhibitors, which are utilized in the treatment of certain forms of cancer.

Alunbrig (brigatinib) is a type of kinase inhibitor that is used to treat patients who have anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) and have either not responded well to or cannot tolerate crizotinib.

The list price of brigatinib is £4900.00 (excluding VAT; BNF accessed November 2020) for the following options:
– Starter pack: This includes 7 tablets at 90 mg and 21 tablets at 180 mg.
– 28-tablet pack: This pack contains 28 tablets at 180 mg.

Additionally, the company has a commercial arrangement in place, which is a simple discount patient access scheme.

ALUNBRIG is approved for treating metastatic non-small cell lung cancer (NSCLC) in adult patients who have tested positive for the anaplastic lymphoma kinase (ALK) gene using an FDA-approved test.

The suggested amount of ALUNBRIG® (brigatinib) is 90 mg taken orally once a day for the initial 7 days. Afterward, the dosage should be raised to 180 mg taken orally once a day.

Mechanism of Action: Alunbrig (brigatinib) is a kinase inhibitor that effectively targets several kinases, including ALK, ROS1, IGF-1R, FLT-3, and EGFR deletion and point mutations. It exhibits its inhibitory effects at clinically achievable concentrations.

Brigatinib (ALUNBRIG, ARIAD Pharmaceuticals Inc.) was approved by the Food and Drug Administration on May 22, 2020 for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) who test positive for anaplastic lymphoma kinase (ALK) using an FDA-approved test.

The ALK receptor, which is a tyrosine kinase located on the cell membrane, plays a significant role in the development of various cancers. Abnormal forms of ALK or abnormal expression of ALK, such as ALK fusion proteins, ALK-activated point mutations, and ALK amplification, are closely associated with the pathogenesis of these cancers.

Indomethacin, an NSAID, is prescribed for the treatment of mild to moderate acute pain and to alleviate symptoms of arthritis (osteoarthritis and rheumatoid arthritis) or gout. It effectively reduces inflammation, swelling, stiffness, and joint pain.

Anlotinib has been approved in China as a 3rd line treatment for locally advanced or metastatic non-small cell lung cancer and as a 2nd line treatment for advanced soft-tissue sarcoma. It has a low half-maximal inhibitory concentration (IC50) of 0.2 nM and exhibits potent inhibitory activities on FGFR.

Indomethacin, also known by its brand names Indocin® and Tivorbex®, is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce inflammation and treat severe pain, inflammation, or arthritis. It is available in tablet form.

To ensure optimal absorption and minimize potential stomach issues, it is recommended to take Gleevec with a meal and a generous amount of water. Avoid taking Gleevec on an empty stomach as it may lead to digestive tract irritation or more severe stomach problems.

Researchers have discovered that individuals with stage 4 ALK-positive lung cancer can achieve a median survival of 6.8 years through appropriate treatment, which is significantly higher than the overall survival rates of 25% for NSCLC and 2 to 7% for advanced-stage lung cancer.

About 90% of those diagnosed with ALK-positive cancer are diagnosed when the cancer has already spread to other parts of the body (known as metastatic cancer, or stage 4 cancer) Without any cancer treatment, half of patients with metastatic ALK cancer would die within less than 12 months.

The prognosis of lung cancer is largely determined by its stage. Non-small lung cancer in its early stages (0 and 1) has a more favorable prognosis compared to later stages (2, 3, or 4). Similarly, limited stage small cell lung cancer has a better prognosis than extensive stage cancers.

On August 9, 2023, Genentech, Inc.’s pralsetinib (Gavreto) received regular approval from the FDA for the treatment of non-small cell lung cancer in patients with RET gene fusions.

On October 11, the FDA granted approval for the combination of targeted drugs encorafenib (Braftovi®) and binimetinib (Mektovi®) for individuals with metastatic non-small cell lung cancer who have a BRAF V600E mutation. This combination, which is administered orally in pill form, was previously approved for certain individuals with melanoma.

Braftovi (encorafenib) in combination with Mektovi (binimetinib) has been approved by the FDA for treating metastatic non-small cell lung cancer (NSCLC) in adult patients.

Crizotinib (Xalkori) is a potential treatment for stage 4 non-small cell lung cancer that is ALK-positive. In cases where crizotinib cannot be taken, alternative drugs such as ceritinib (Zykadia), alectinib (Alecensaro), or brigatinib (Alunbrig) may be prescribed.

The cost of chemotherapy drugs can vary between $1,000 and $12,000 per monthly dose. Therefore, the total cost of these drugs for a year of treatment can reach up to $50,000.

Pfizer (NYSE: PFE) has received approval from the U.S. Food and Drug Administration (FDA) for the use of BRAFTOVI® (encorafenib) + MEKTOVI® (binimetinib) in the treatment of metastatic non-small cell lung cancer (NSCLC) in adult patients with a BRAF V600E mutation. This approval is contingent upon the use of an FDA-approved test to detect the mutation.

EGFR inhibitors are utilized in the treatment of NSCLC with EGFR gene mutations. In the case of earlier stage NSCLC, Osimertinib may also be prescribed as an adjuvant treatment following surgery for certain EGFR gene mutations. These medications are administered in pill form.

The CHOICE-01 trial demonstrated promising results for the newer immunotherapy toripalimab when used in combination with chemotherapy as a first-line treatment for NSCLC patients without EGFR or ALK mutations. This suggests that toripalimab could provide an additional immunotherapy-based treatment option for individuals with this type of lung cancer.

ALK-positive lung cancer is highly responsive to ALK inhibitors, a class of targeted drugs. Additionally, chemotherapy and other medications have shown efficacy against this type of cancer. However, it is common for the cancer to recur following treatment. The prognosis for individuals with ALK-positive lung cancer is influenced by the stage at which it is diagnosed.

Metastatic lung cancer refers to the type of cancer that originates in one lung and then spreads to the other lung or other organs. Treating metastatic lung cancer is more challenging compared to cancer that remains confined to its initial site.

However, when the gene is reactivated and combines with another gene, it can result in an ALK rearrangement or fusion, leading to the development of ALK-positive lung cancer. ALK-positive lung cancer accounts for only approximately 4% of all lung cancer cases and is predominantly observed in non-small cell lung cancer.

The prognosis of lung cancer is largely determined by its stage. Non-small lung cancer in its early stages (0 and 1) has a more favorable prognosis compared to later stages (2, 3, or 4). Similarly, limited stage small cell lung cancer has a better prognosis than extensive stage cancers.

Stage IV is the most advanced stage of lung cancer, indicating that the disease has spread to distant parts of the body, such as the liver or brain. Unfortunately, this form of cancer is extremely difficult to cure. It is alarming that approximately 90% of individuals with ALK-positive lung cancer are only diagnosed at stage IV, when the disease has already progressed significantly.

When the ALK gene fuses or rearranges with another gene, it can lead to the development of cancer, specifically lung cancer. In such cases, the patient is referred to as ALK-positive. The ALK gene has the ability to fuse with various genes, with the most frequently observed fusion being with the EML4 gene.

The FDA has approved four ALK-TKI drugs for the treatment of ALK-positive lung cancer. These include crizotinib as the first generation drug, and alectinib, ceritinib (Zykadia; Novartis), and brigatinib (Alunbrig; Ariad/Takeda) as second generation drugs.

Despite receiving surgery, chemotherapy, anti-ALK, and anti-infective therapy, the child in this study unfortunately died of intracranial infection, which is contrary to the generally good prognosis of ALK-positive histiocytosis described in the literature.

The standard treatment for ALK-positive ALCL remains the CHOP/CHOP-like regimen, which includes cyclophosphamide, doxorubicin, vincristine, and prednisone. This treatment has shown a 5-year overall survival rate of 70-90%.

Patients with previously untreated advanced ALK-positive NSCLC are found to have better outcomes when treated with ALK inhibitors compared to standard first-line pemetrexed plus platinum chemotherapy.

The 5-year OS rates for alectinib and crizotinib were 60.9% (95% CI 51.4-70.3) and 64.1% (95% CI 54.9-73.4), respectively. Despite this, alectinib is still considered the preferred standard of care for treating patients with advanced ALK-positive NSCLC.