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Lung ๐Ÿ›ก๏ธ Preventing recurrence

The ALINA trial: a targeted pill after surgery for ALK-positive lung cancer

For early-stage lung cancer driven by the ALK gene, taking a targeted pill (alectinib) for two years after surgery — instead of chemotherapy — sharply lowered the chance the cancer came back, and was especially good at preventing it from spreading to the brain.

~9 min readPhase IIINEJM2024

Who is this for?

This is for people with early-stage, ALK-positive non-small-cell lung cancer that has been completely removed by surgery — specifically stage IB (larger tumors), II, or IIIA.

ALK-positive lung cancer is uncommon (about 4–5% of non-small-cell lung cancers). The people who have it tend to be younger, and often never-smokers. It is driven by a specific rearrangement in a gene called ALK — and that same feature makes it treatable with targeted pills.

The key terms, in plain language ALK-positive means the cancer is driven by a change in the ALK gene, found on a lab test of the tumor. Adjuvant treatment is given after surgery to lower the chance the cancer comes back. Alectinib is a targeted pill — an “ALK inhibitor” (a type of TKI) — that switches off the ALK driver. Disease-free survival is the length of time a person stays alive and free of any cancer recurrence.

What kind of trial is this?

ALINA was a global phase III randomized trial — the most rigorous kind. It compared two years of adjuvant alectinib against the old standard, adjuvant chemotherapy, in people whose ALK-positive lung cancer had been surgically removed.

Understanding the disease
Finding cancer earlier
Preventing recurrence
Treating the cancer
Feeling better during treatment
First steps in humans
How we make decisions

Background: surgery, then what?

Even after a lung cancer is completely removed by surgery, cells can have already escaped, and the cancer comes back in a substantial share of people — more often the more advanced the stage. For years, the only tool to lower that risk was adjuvant chemotherapy, which helps only modestly (roughly a 5% improvement in survival) and can be hard to tolerate.

Meanwhile, in advanced ALK-positive lung cancer, alectinib was already a highly effective targeted pill. ALINA asked the natural next question: if we give this pill early, right after surgery, can we keep the cancer from coming back? This mirrors the story of the ADAURA trial, which asked the same question for the targeted pill osimertinib in EGFR-mutated lung cancer.

Two years after surgery: alectinib vs chemotherapy Bar chart. Free of any recurrence at 2 years: 93.6 percent with alectinib versus 63.7 percent with chemotherapy. Brain still free of cancer at 2 years: 98.4 percent with alectinib versus 85.8 percent with chemotherapy. Alectinib (targeted pill) Chemotherapy Free of any recurrence at 2 years Alectinib 93.6% Chemo 63.7% Brain still free of cancer at 2 years Alectinib 98.4% Chemo 85.8% 0% 100%
Two years after surgery, far more people who took alectinib were still free of any cancer recurrence (93.6% vs 63.7%), and alectinib was especially good at keeping the cancer out of the brain — a place ALK-positive lung cancer often spreads.

The trial: what was tested and how

ALINA enrolled 257 people whose ALK-positive lung cancer had been completely removed by surgery. They were randomly assigned to one of two groups:

  • Alectinib (130 people): the targeted pill, taken twice daily for 2 years.
  • Chemotherapy (127 people): the standard adjuvant platinum-based chemotherapy, given over about 3 months.

The main measure was disease-free survival — how long people stayed alive and free of any recurrence.

Results: what they found

Adjuvant alectinib dramatically lowered the chance the cancer came back, and it was strikingly effective at protecting the brain.

Alectinib pill vs chemotherapy, after surgery

Free of any recurrence at 2 years
93.6%Alectinib vs 63.7%Chemotherapy

The risk of the cancer returning or death was 76% lower with alectinib (HR 0.24). The benefit held across every subgroup.

Cancer spread to the brain
3.1%Alectinib vs 11.0%Chemotherapy

ALK-positive lung cancer has a strong tendency to spread to the brain. Alectinib — which reaches the brain well — cut brain recurrences to a third (HR 0.22).

Serious side effects
18%Alectinib, grade 3–4 vs 27.5%Chemotherapy

Despite being taken for two years, alectinib caused fewer severe side effects than 3 months of chemotherapy. Its common effects — mostly mild — were lab changes and constipation. No fatal side effects occurred.

What is ALK-positive lung cancer?

In a small share of lung cancers, a gene called ALK becomes fused to another gene, producing an always-on growth signal that drives the cancer. A lab test on the tumor detects it. Because the cancer depends on this one faulty switch, drugs that block ALK (like alectinib) can be remarkably effective — and they tend to work whether the person smoked or not.

How is this like the ADAURA trial?

Very similar in spirit. ADAURA showed that the targeted pill osimertinib, given after surgery, sharply reduced recurrence in EGFR-mutated lung cancer — and later showed people lived longer. ALINA is the ALK-positive counterpart: a different gene, a different pill, but the same idea — use a targeted therapy early to keep the cancer from coming back.

Does it help people live longer?

It is too early to know. The main result here is disease-free survival — staying free of recurrence — which is a well-established goal in this setting. Overall-survival data were not yet mature (very few deaths had occurred), so longer follow-up is needed. In the closely related ADAURA trial, a large recurrence benefit was later shown to translate into longer survival, which is encouraging but not a guarantee here.

Look up this trial ALINA · Adjuvant alectinib vs chemotherapy in resected ALK-positive NSCLC · NCT03456076
View on ClinicalTrials.gov →

The bottom line

For people whose early-stage, ALK-positive lung cancer has been surgically removed, two years of the targeted pill alectinib dramatically lowered the chance of recurrence compared with chemotherapy (2-year disease-free survival 93.6% vs 63.7%) — and was especially good at preventing spread to the brain. It also caused fewer serious side effects than chemotherapy. Whether this translates into longer overall survival isn’t known yet, but the recurrence benefit is large and has made adjuvant alectinib a new standard for this group.

What this could mean for you

  • Ask whether your tumor was tested for ALK. If a lung cancer has been resected, knowing whether it is ALK-positive opens up this option.
  • A pill, not an IV. Adjuvant alectinib is taken at home for two years; most side effects are manageable.
  • Brain protection matters. Because this cancer often spreads to the brain, a treatment that reaches the brain is a meaningful advantage.
  • It’s a commitment. Two years of daily treatment with monitoring — worth discussing what that involves with your team.
For information purposes only. This summary explains published research in plain language. It is not medical advice and is not a substitute for care from your own doctors. Trial results describe what happened in a study group and may not apply to your situation. Always discuss your diagnosis, treatment options, and any clinical trial with your own oncology team before making any decisions.

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