Research May 2026

Lorviqua (lorlatinib) in ALK-positive NSCLC. 7-year CROWN data, first-line

Q: What does ALK-positive NSCLC mean?

It is non-small cell lung cancer in which tumor cells carry a rearrangement of the ALK gene. This finding matters for treatment choice: ALK-positive NSCLC can be treated with specific targeted drugs — ALK inhibitors. Without molecular testing this target can be missed.

Q: Should therapy be changed urgently if a patient is already on another ALK inhibitor?

Not necessarily. If the disease is controlled, the therapy is acceptably tolerated and there are no signs of progression, a switch should not be made solely on the basis of a news item. The current response, duration of control, toxicity and possible switching risks all need to be assessed.

At the ASCO 2026 Annual Meeting, 7-year data from CROWN were presented — an international, randomized, open-label phase III trial in previously untreated, advanced ALK-positive non-small cell lung cancer. The trial compared Lorviqua (lorlatinib) and Xalkori (crizotinib).

The headline number of the update: at 7 years, the probability of being alive and progression-free was 55% in the lorlatinib arm versus 3% in the crizotinib arm. Median progression-free survival on lorlatinib has still not been reached; on crizotinib it was 9.1 months (HR 0.19).

This news matters most for patients with ALK-positive NSCLC, for whom targeted therapy is an option. But real practice is broader. CROWN compared lorlatinib with crizotinib, while today the first-line question often is how to choose among several current ALK inhibitors with different efficacy, toxicity and intracranial control profiles.

What happened in brief

At ASCO 2026, 7-year data from CROWN — a phase III trial of lorlatinib versus crizotinib in first-line advanced ALK-positive NSCLC — were presented.
Total 296 patients: Lorviqua (lorlatinib) 100 mg once daily — 149 patients; Xalkori (crizotinib) 250 mg twice daily — 147 patients.
Median follow-up: 83.0 months in the lorlatinib arm and 77.2 months in the crizotinib arm.

Key numbers

Progression-free survival (PFS)

median PFS on lorlatinib — not reached;
median PFS on crizotinib — 9.1 months;
lower risk of progression or death in the lorlatinib arm (HR 0.19);
7-year PFS: 55% vs. 3%.

Intracranial progression

median time to intracranial progression on lorlatinib — not reached;
on crizotinib — 16.4 months;
lower risk of intracranial progression in the lorlatinib arm (HR 0.06);
7-year intracranial progression-free survival — 92% vs. 16%;
after the first 30 months in the lorlatinib arm there were no new intracranial progression events.

Additional

between years 5 and 7 there were 7 new PFS events in the lorlatinib arm (4 progressions and 3 deaths, not related to treatment per the source);
at the time of analysis, 44% of patients in the lorlatinib arm were still on therapy, vs. 3% in the crizotinib arm.

Mature final overall survival data are not yet reported in this 7-year update. Follow-up is ongoing; OS results will be reported later.

Toxicity

no new safety signals were identified in the 7-year analysis;
any-cause grade 3–4 adverse events: 77% in the lorlatinib arm vs. 57% in the crizotinib arm;
common adverse events of interest with lorlatinib: edema, weight gain, peripheral neuropathy, cognitive effects, mood changes, diarrhea, dyspnea, arthralgia, arterial hypertension, headache, cough, fever, hypercholesterolemia and hypertriglyceridemia;
permanent discontinuation due to treatment-related adverse events: 5% on lorlatinib and 6% on crizotinib;
after the first 26 months in the lorlatinib arm there were no new permanent discontinuations due to treatment-related adverse events.

Commentary by Evgeny Ledin

Let me start with the main point. The 7-year CROWN data are perhaps one of the most impressive examples of long-term control of stage IV ALK-positive lung cancer on oral targeted therapy. At seven years of follow-up, more than half of patients on lorlatinib are still alive without disease progression. For metastatic NSCLC, this is a very strong result. But it is critical to remember: it applies not to all patients with lung cancer, but only to those with a confirmed ALK rearrangement.

Lorviqua (lorlatinib) is registered in Russia for first-line therapy of ALK-positive advanced NSCLC, so this is not just academic news from an international congress — these data can be discussed in real clinical practice. They reinforce the importance of molecular diagnostics before treatment. You cannot choose therapy based only on "stage IV lung cancer" or "lung adenocarcinoma". The molecular profile of the tumor has to be known.

The critical part of these data is no less important than the numbers themselves. CROWN compared lorlatinib with crizotinib. Crizotinib was a very important drug for its time, but today the first-line question in ALK-positive NSCLC is often framed as a choice among current ALK inhibitors, including Lorviqua (lorlatinib), Alecensa (alectinib) and Alunbrig (brigatinib). So 55% vs. 3% cannot be mechanically translated into "lorlatinib is better than any other modern ALK inhibitor for every patient". It is a strong argument in favor of the drug, but not a direct comparison with all current alternatives.

Another important nuance: 7-year PFS is not the same as final overall survival. Progression-free survival shows how long the disease does not progress. This is a crucial measure, especially in metastatic ALK-positive lung cancer. But final conclusions about overall survival require mature OS data, which are not yet available.

Finally, lorlatinib is not just "a pill". With long-term treatment, cognitive, psychoemotional, metabolic and neurological adverse events matter, as do monitoring of lipid profile, weight, blood pressure, drug interactions, memory, attention and mood.

My bottom line: the 7-year CROWN data strengthen the position of Lorviqua (lorlatinib) as one of the key first-line options in advanced ALK-positive NSCLC, especially when long-term control and prevention of intracranial progression are important. But the right treatment choice has to take into account CNS involvement, comorbidities, expected tolerability, quality of life and alternative options. If first-line therapy is still being chosen, these data are worth discussing on a consultation or as part of a second opinion.

Get a second opinion

When a second opinion is especially useful

if ALK-positive NSCLC has been confirmed and first-line therapy is being chosen;
if molecular testing was not performed, was incomplete, or the result is unclear;
if there are brain metastases and therapy has to be chosen with CNS control in mind;
if a single treatment option is being proposed but the patient wants to understand alternatives and how they differ;
if cognitive, metabolic, neurological or cardiovascular adverse events have appeared on an ALK inhibitor;
if the disease is progressing on an ALK inhibitor and a decision is needed about a repeat biopsy, liquid biopsy or extended genomic profiling.

What to prepare for the consultation

histopathology report;
IHC, FISH or NGS report for ALK, if performed;
extended molecular testing results, if performed;
discharge summaries from prior treatment;
CT, MRI, PET-CT results;
brain MRI, especially if there are or were CNS metastases;
PD-L1 and other biomarkers, if assessed;
blood tests including lipid panel, glucose, liver and kidney function;
list of comorbidities and regular medications;
description of adverse events if the patient is already on targeted therapy.

Sources:

Frequently Asked Questions

What does ALK-positive NSCLC mean?

Non-small cell lung cancer in which tumor cells carry a rearrangement of the ALK gene. This matters for treatment: ALK-positive NSCLC can be treated with specific targeted drugs — ALK inhibitors. Without molecular testing this target can be missed.

Is Lorviqua (lorlatinib) suitable for all patients with lung cancer?

No. Lorviqua (lorlatinib) is for ALK-positive advanced NSCLC. If no ALK rearrangement is found, these data do not apply. Other molecular drivers (EGFR, ROS1, BRAF, MET, RET, KRAS G12C) or driver-negative disease are treated differently.

Is this already a new first-line standard?

The 7-year CROWN data reinforce lorlatinib as one of the key first-line options in ALK-positive advanced NSCLC. But the standard for a given patient depends on efficacy, toxicity, comorbidities, brain involvement risk and drug availability.

Should therapy be changed urgently if a patient is already on another ALK inhibitor?

Not necessarily. If the disease is controlled and tolerated, a switch should not be made solely on the basis of a news item. Current response, duration of control, toxicity and switching risks have to be assessed.

What is the difference between PFS and overall survival?

PFS — progression-free survival — is the time to disease progression or death. OS — overall survival — is the duration of life regardless of progression. In the 7-year CROWN update, PFS data are mature; mature final OS data are not yet reported.

Is lorlatinib available in Russia?

Lorlatinib is registered in Russia under the trade name Lorviqua. The Russian label specifies use in the first-line setting in adults with ALK-positive advanced NSCLC. Actual availability and routing depend on the clinical situation, region and drug supply system.