ALK-Positive Lung Cancer & Targeted Therapies

About 1 in 25 non-small cell lung cancers carries a change in a gene called ALK. Two genes fuse together in the tumor's cells, creating an abnormal protein that drives the cancer to grow. This is not something you inherited. It happened in the tumor cells only. Testing tumor tissue, or sometimes blood, for this fusion is now standard. This applies to people with non-small cell lung cancer, especially adenocarcinoma. It matters most for people who never smoked or smoked only lightly.

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. For this specific group of cancers, they often work better than standard chemotherapy, and cause different side effects. Ask whether your tumor was tested for ALK, and whether you received the result before treatment started.

Several ALK inhibitors are approved: alectinib, brigatinib, lorlatinib, ceritinib, and crizotinib. Alectinib and brigatinib are commonly used as a first treatment. Lorlatinib, a newer drug, has also shown strong results as an initial treatment in recent studies. These are daily pills, not infusions, which is different from typical chemotherapy schedules.

Not all ALK inhibitors are interchangeable. Newer ones, such as alectinib, brigatinib, and lorlatinib, cross into the brain better than the original drug, crizotinib. This matters because ALK-positive lung cancer can 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. Sometimes they retest the tumor first, to see exactly how it changed. This retesting can guide which drug is tried next.

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 needs prompt evaluation. 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.
• Call your care team the same day if your breathing has become harder over a few days, a new or changing cough has appeared, or you have a temperature of 100.4°F (38°C) or higher. Drug-related lung inflammation is treatable, and teams would far rather see you early than late.
• One exception on that temperature. If chemotherapy is running alongside the ALK inhibitor, or finished within the past few weeks, 100.4°F (38°C) is not a same-day call. CDC rates a fever during chemotherapy a medical emergency: ring the team at once whatever the hour, and go to an emergency department if you cannot get through.
• Call your care team within a day or two if your vision blurs or doubles, your eyes trail moving objects oddly, your ankles or hands puff up, or people close to you notice your mood, speech or memory shifting. Yellowing of the eyes or skin, dark urine, or muscle aching that stops you walking normally belongs here too.

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).
• National Cancer Institute — Lorbrena Effective as Initial Treatment of ALK-Positive NSCLC.