ALK-Positive Lung Cancer & Targeted Therapies

This page is for people with non-small cell lung cancer, and their families, who want to understand ALK testing and ALK-targeted pills. It covers what ALK-positive means, the drugs used, and which side effects need a call.

About 5% of people with non-small cell lung cancer have a change in a gene called ALK. The change makes an abnormal protein that helps the cancer grow. People with this cancer tend to be younger than others with lung cancer. They tend to have smoked lightly or never smoked. Your doctor may suggest biomarker tests on the tumor to look for it.

Finding an ALK change opens the door to targeted therapy. These are pills designed to block the specific abnormal protein the fusion creates. These drugs are called ALK inhibitors. Ask whether your tumor was tested for ALK, and whether you received the result before treatment started.

Several ALK inhibitors are FDA-approved for ALK-positive non-small cell lung cancer that has spread:

• alectinib
• brigatinib
• lorlatinib
• ceritinib
• crizotinib

In a large trial, lorlatinib worked better than crizotinib as a first treatment. Alectinib is also approved after surgery for some people. These are daily pills, not infusions, which is different from typical chemotherapy schedules.

Not all ALK inhibitors are interchangeable. Lorlatinib was designed to cross into the brain. This matters because ALK-positive lung cancer tends to spread to the brain. Your team's choice depends on your specific case, whether cancer has reached the brain, and side-effect concerns.

Over time, cancer can develop new changes. These can make it resistant to an ALK inhibitor. When this happens, your team may switch to a different ALK inhibitor, or add other treatments.

ALK inhibitors can cause side effects. These include liver test changes, muscle pain, and vision changes. Mood or memory changes, high cholesterol, swelling, and lung inflammation can also happen. Lung inflammation from these drugs can be severe or life-threatening. The section below sets out which of these cannot wait.

• Was my tumor tested for an ALK gene fusion, and what was the result?
• Which ALK inhibitor is recommended for me, and why this one?
• Does this drug cross into the brain, and does that matter for my case?
• What side effects should I report right away versus at my next visit?
• If this drug stops working, what would come next?

• Call 911 or go to an emergency department if you are struggling to breathe at rest, your lips or fingertips look blue or grey, or you become confused or faint. Sudden severe chest pain or a first-ever seizure needs the same response. Do not drive yourself.
• Call your care team right away, at any hour, if you have a temperature of 100.4°F (38°C) or higher while chemotherapy is running alongside the ALK inhibitor, or finished within the past few weeks. CDC rates a fever during chemotherapy a medical emergency. Go to an emergency department if you cannot get through, and say you are on chemotherapy.
• Call your care team right away if your breathing has become harder, a new or changing cough has appeared, or you have a temperature of 100.4°F (38°C) or higher. The drug labels say to report new or worse breathing problems right away. Also call right away for yellow skin or eyes, dark urine, muscle pain you cannot explain, new swelling in your legs or feet, or sudden loss of vision.
• Call your care team within a day or two if your vision blurs or doubles, you see flashes or floaters, or people close to you notice your mood, speech or memory shifting.

While you are on an ALK inhibitor, take the tablet's name with you to any urgent care visit. It changes what the team looks for.

• National Cancer Institute — Non-Small Cell Lung Cancer Treatment (PDQ).
• FDA labels (DailyMed) for Alecensa, Alunbrig, Lorbrena, Zykadia and Xalkori.
• National Cancer Institute — Lorbrena Effective as Initial Treatment of ALK-Positive NSCLC.