Brigatinib-Alunbrig Receives FDA Approval for First-Line Treatment of ALK-Positive Stage 4 Lung Cancer

Alunbrig Receives First-Line FDA Approval 

On 22 May 2020, the FDA (United States Food and Drug Administration) approved, for first-line treatment of patients with an anaplastic lymphoma kinase (ALK) genetic alteration who have metastatic non-small cell lung cancer (NSCLC), the drug brigatinib (marketed as Alunbrig, manufactured by Takeda).

At the same time, the FDA also approved the Vysis ALK Break Apart FISH Probe Kit as a companion diagnostic for brigatinib.

Alunbrig had previously received FDA approval in 2017 for use after crizotinib.

The ALTA 1 Study

Efficacy was investigated in the ALTA 1L clinical trial, a randomized, open-label, multicenter study with a 1:1 allocation in adults with advanced ALK-positive NSCLC who had not previously received ALK-targeted therapy. The trial randomly assigned 275 patients to two arms:

• The 137 patients in the Alunbrig arm took 1 daily dose of 90 mg during the first first week, followed by 1 daily dose of 180 Alunbrig;
• The 138 patients in the crizotinib arm took 2 daily doses of 250 mg crizotinib.

A subset of clinical samples was retrospectively tested for patients' tumors using the Vysis ALK Break Apart FISH Probe Kit. Of the enrolled patients, 239 had ALK-positive results using the Vysis diagnostic test (results were negative for 20 patients and unavailable for 16 patients). The primary efficacy outcome the study sought to measure, assessed by a blinded independent review committee, was progression-free survival (PFS). Additional efficacy outcome measures were defined as overall response rate.

• Estimated median progression-free survival was 24 months in patients treated with Alunbrig and 11 months with crizotinib.
• In this group of patients with ALK-positive advanced NSCLC, using Alunbrig instead of crizotinib reduced the risk of disease progression by 51% (HR 0.49; 95% CI: 0.35, 0.68; p <.0001).
• Confirmed overall response rates were 74% and 62%, respectively.

The most common (≥25%) Alunbrig side effects were diarrhea, fatigue, nausea, rash, cough, muscle pain, headache, hypertension, vomiting and shortness of breath. The recommended Alunbrig dose is 90 mg orally once daily for the first 7 days, increasing thereafter to 180 mg orally once daily. Alunbrig may be taken with or without food.

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What Is Alunbrig's Mechanism of Action?

Alunbrig is an ALK (anaplastic lymphoma kinase) inhibitor. The ALK receptor is a receptor responsible for growth and proliferation, encoded by the ALK gene in humans. When ALK fuses (combines) with EML4, it can trigger lung cancer. This is one of the causes of lung cancer in people who do not smoke. Brigatinib inhibits the activity of this fused gene. The EML4-ALK fusion gene is responsible for approximately 5% of non-small cell lung cancers. This proportion may seem small, but considering that lung cancer is the most common cancer worldwide, it corresponds to 70 thousand new lung cancer patients each year.

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What Is the Status of Alunbrig Use in Turkey? 

In Turkey, Alunbrig, as both first-line and second-line treatment, has SGK (Social Security Institution) reimbursement coverage and, for the following situations, Ministry of Health authorization:

1. Advanced ALK-Positive Non-Small Cell Lung Cancer (NSCLC) without Previous ALK-Targeted Treatment: ALUNBRIG (brigatinib) is indicated for use until progression in the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose anaplastic lymphoma kinase (ALK) positivity has been confirmed by FISH testing.
2. ALK-Positive Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) Previously Treated with Crizotinib: ALUNBRIG (brigatinib) is indicated for use until progression in the treatment of patients previously treated with crizotinib who have advanced or metastatic non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) positivity confirmed by FISH testing.

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