More Than Half of ALK-Positive Lung Cancer Patients Still Stable After Seven Years on Lorlatinib, the CROWN Study Reveals

“We’re talking about seven years — maybe even ten — of keeping the cancer under control, including in the brain.”

Not long ago prior to 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%–5% of patients with 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 did not worsen in seven years, compared to only 3% of patients on crizotinib (Xalkori). Lorlatinib and crizotinib are both drugs in a class called tyrosine kinase inhibitors, which 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, noting that a 94% reduction in the risk of progression of brain metastases (cancer spreading to the brain). After 30 months, no new brain metastases (cancer spreading) were seen in patients on lorlatinib.

Dr. Shaw emphasized how important this is by adding that, “Lorlatinib doesn’t just treat brain metastases — it may actually prevent them. That’s incredibly important for quality of life and long‑term survival.”

Side Effects and Long‑Term Use

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 in just over two years (26 months).

Known side effects of lorlatinib may include the following:

• Edema
• Peripheral neuropathy
• Weight gain
• Cognitive effects
• Fatigue
• Dyspnea
• Arthralgia
• Diarrhea
• Mood effects
• Hypercholesterolemia
• Hypertriglyceridemia
• 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 told SurvivorNet.

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 the strongest first-line treatment option, especially because of its brain-protective effects.
• Dose adjustments are okay and don’t make the treatment less effective.
• 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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