What is the recommended first-line treatment for a patient with stage 4 metastatic adenocarcinoma (lung cancer) that is anaplastic lymphoma kinase (ALK) positive?

From the Guidelines

The recommended first-line treatment for a patient with stage 4 metastatic ALK-positive lung adenocarcinoma is an ALK tyrosine kinase inhibitor (TKI), with alectinib (Alecensa) at a dose of 600 mg twice daily being the preferred initial therapy due to its superior efficacy and CNS penetration, as supported by the most recent and highest quality study 1.

Key Considerations

• Alectinib has shown a longer progression-free survival (PFS) and lower toxicity compared to crizotinib, with activity against CNS disease in previously untreated patients with ALK-positive NSCLC 1.
• Alternative ALK inhibitors include brigatinib (Alunbrig) 90 mg once daily for 7 days followed by 180 mg once daily, or lorlatinib (Lorbrena) 100 mg once daily, which have also demonstrated efficacy in treating ALK-positive NSCLC 1.
• These medications are taken orally and treatment continues until disease progression or unacceptable toxicity.
• Regular monitoring for side effects is essential, including liver function tests every 2 weeks for the first 3 months and then monthly.

Rationale

• ALK inhibitors target the specific molecular driver of the cancer by blocking the abnormal ALK fusion protein that promotes tumor growth.
• This targeted approach offers higher response rates (60-80%), longer progression-free survival (up to 34 months with alectinib), and better quality of life compared to traditional chemotherapy.
• ALK inhibitors are particularly effective because they can penetrate the blood-brain barrier to address brain metastases, which are common in ALK-positive disease.

Supporting Evidence

• The 2024 study published in the Journal of the National Comprehensive Cancer Network 1 provides the most recent and highest quality evidence supporting the use of alectinib as the preferred first-line treatment for ALK-positive NSCLC.
• The 2022 study published in the Journal of Clinical Oncology 1 also recommends alectinib or brigatinib as the first-line treatment for patients with ALK rearrangement and previously untreated NSCLC.

From the FDA Drug Label

ALECENSA is a kinase inhibitor indicated for: treatment of adult patients with ALK-positive metastatic NSCLC as detected by an FDA-approved test. LORBRENA® is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.

The recommended first-line treatment for a patient with stage 4 metastatic adenocarcinoma (lung cancer) that is anaplastic lymphoma kinase (ALK) positive is alectinib (ALECENSA) or lorlatinib (LORBRENA), as both are indicated for the treatment of adult patients with ALK-positive metastatic NSCLC 2 3.

• The dosage of alectinib (ALECENSA) is 600 mg orally twice daily, administered with food.
• Lorlatinib (LORBRENA) dosage is not specified in the provided text, so it is recommended to consult the full prescribing information for the correct dosage.

From the Research

Treatment Overview

• The recommended first-line treatment for a patient with stage 4 metastatic adenocarcinoma (lung cancer) that is anaplastic lymphoma kinase (ALK) positive is alectinib, a potent and highly selective ALK tyrosine kinase inhibitor 4.
• Alectinib is approved in the EU as first-line treatment for adults with advanced ALK-positive non-small cell lung cancer (NSCLC) and for the treatment of adults with advanced ALK-positive NSCLC previously treated with crizotinib 4.
• In the USA, alectinib is indicated for the treatment of adults with ALK-positive metastatic NSCLC 4.

Dosage and Administration

• The recommended dosage for alectinib in the EU and USA is 600 mg twice daily 4.
• However, a lower dose of 300 mg twice daily may be considered for specific patient populations, such as those with a lower body weight, to limit treatment disruptions and dose reductions 5.
• Dose escalation to 900 mg twice daily may be considered in cases of CNS progression, as seen in a case report where a patient with ALK-positive leptomeningeal metastasis achieved clinical benefits with dose escalation 6.

Efficacy and Safety

• Alectinib has shown significant improvement in progression-free survival (PFS) and central nervous system (CNS)-related outcomes compared to crizotinib as first-line therapy and chemotherapy in patients previously treated with crizotinib and platinum-doublet chemotherapy 4.
• Alectinib has a manageable tolerability profile, with most adverse events (AEs) of mild or moderate severity 4.
• Common adverse events include constipation, fatigue, myalgia, and peripheral edema, with grade 3 and 4 adverse events being rare 7.

Special Considerations

• Alectinib may be a suitable treatment option for patients with crizotinib-induced interstitial lung disease (ILD), as seen in a case report where a patient achieved tumor shrinkage without any recurrence of ILD after switching to alectinib 8.
• Sequential ALK inhibitor treatment, including alectinib and lorlatinib, may be effective in overcoming ALK inhibitor resistance in the CNS, as seen in a case report where a patient with ALK-positive leptomeningeal metastasis achieved clinical benefits with sequential treatment 6.