Lasting Control for ALK Lung Cancer
- More than half of people with ALK-positive lung cancer, a type driven by an abnormal ALK gene, were still doing well seven years after starting lorlatinib, a result almost never seen in advanced lung cancer, the CROWN study found.
- Lorlatinib greatly lowered the risk of the cancer worsening or spreading, including a 94% reduction in the risk of cancer growing or spreading in the brain.
- Most patients can stay on the medicine long-term, and dose adjustments are common and don’t reduce its effectiveness. For many, lorlatinib may help turn ALK-positive lung cancer into a condition that can be managed for years.
The latest results from the CROWN study didn’t just confirm that lorlatinib works well; this study showed something almost unheard of in advanced lung cancer.
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“We’re not talking about months anymore,” Dr. Shaw says.“We’re talking about seven years — maybe even ten — of keeping the cancer under control, including in the brain.”
Before targeted drugs, people with metastatic ALK‑positive lung cancer often lived a year or less. Now, the conversation is completely different.
ALK is a receptor tyrosine kinase — a type of signaling protein — that is normally inactive in adults. In about 3% to 5% of patients with non-small cell lung cancer (NSCLC), a chromosomal rearrangement fuses the ALK gene with another gene (most commonly EML4), creating an abnormal, always-on fusion protein that drives cancer growth.
What the Numbers Mean for You
At seven years:
- 55% of patients on lorlatinib were still progression‑free, meaning the cancer had not worsened in seven years, compared to only 3% of patients on crizotinib (Xalkori). Lorlatinib and crizotinib are both tyrosine kinase inhibitors that target ALK.
- This means lorlatinib lowered the risk of the cancer worsening or causing death by 81%.
- The protection in the brain was even stronger, with a 94% reduction in the risk of cancer growing or spreading in the brain. After 30 months, no new brain progression was seen in patients on lorlatinib.
Dr. Shaw says, “Lorlatinib doesn’t just treat brain metastases — it may actually prevent them. That’s incredibly important for quality of life and long‑term survival.”
Export Resources for ALK-Positive Non-Small Cell Lung Cancer Patients
- Progress Treating Lung Cancer With ALK-Positive Mutations — The Drug Lorlatinib Shows Major Benefit For Progression Free Survival
- Targeted Gene Therapy and Lung Cancer Treatment– The Hope In ALK Positivity
- Unprecedented Progression-Free Survival for ALK-Positive Non-Small Cell Lung Cancer Using Lorbrena — What the New Research Means for Patients
Side Effects and Long‑Term Use
Serious (grade 3 or 4) side effects occurred in 77% of patients on lorlatinib, compared with 57% on crizotinib, most often high cholesterol and triglycerides.
About one-third (34%) of patients needed a lower dose at some point, but this did not reduce the treatment’s effectiveness.
Only 5% of patients stopped treatment because of side effects, and all of those happened within the first 26 months.
Known side effects of lorlatinib may include the following:
- Swelling (edema)
- Numbness or tingling in the hands and feet (peripheral neuropathy)
- Weight gain
- Changes in thinking or memory
- Fatigue
- Shortness of breath
- Joint pain
- Diarrhea
- Mood changes
- High cholesterol and triglycerides
- Cough
For more information about lorlatinib and to determine if it might be an effective part of your treatment plan, consult your health care provider.
Are We Talking About a Cure?
We asked Dr. Shaw the question many patients wonder about: Are we getting close to a cure?
She was hopeful but careful.
“Many patients have no signs of cancer, which is wonderful. But they still need to stay on treatment. So it depends on how you define ‘cure.’ What we can say is that this is long‑term, lasting control of the disease,” Dr. Shaw explains.
What Happens if the Cancer Eventually Grows?
For patients who do progress on lorlatinib, the next steps are more complicated. There is no standard treatment yet for cancer that becomes resistant to lorlatinib, and clinical trials are very important.
New drugs like neladalkib (NVL‑655) are being studied and may help patients in the future.
What This Means for Patients Today
For most people living with ALK‑positive lung cancer:
- Lorlatinib is now one of the strongest first-line treatment options, especially because of its brain-protective effects.
- Dose adjustments are okay and don’t reduce effectiveness.
- If the cancer grows later, clinical trials are an important option.
Dr. Shaw, who has treated ALK‑positive lung cancer for more than 20 years, put this meaningful progress into perspective.
“These patients used to have a very poor outlook. Now we’re seeing survival beyond seven years. Lorlatinib shows that ALK‑positive lung cancer may become more like a chronic condition — something you live with and manage, rather than something that defines your future.”
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