Lorlatinib for untreated ALK-positive advanced non-small-cell lung cancer

1.1 Lorlatinib is not recommended, within its marketing authorisation, for treating anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC) in adults who have not had an ALK inhibitor.

1.2 This recommendation is not intended to affect treatment with lorlatinib that was started in the NHS before this guidance was published. People having treatment outside this recommendation may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop.

Why the committee made these recommendations

People with ALK‑positive advanced NSCLC who have not had an ALK inhibitor before usually have alectinib or brigatinib in NHS practice. Ceritinib and crizotinib are also available but are rarely used. Lorlatinib is already used after alectinib or brigatinib. It is now being proposed as an alternative to alectinib or brigatinib as a first treatment.

Clinical trial evidence suggests that lorlatinib improves the amount of time people have before their condition progresses compared with crizotinib. But crizotinib is not usually used as a first treatment for this condition, so the trial results are not generalisable to the NHS. An indirect comparison suggests that lorlatinib may increase how long people live before their condition gets worse compared with alectinib and brigatinib, but this is uncertain. Also, because the clinical trial is ongoing, it is not possible to conclude whether this difference will continue and whether lorlatinib will increase how long people live.

Because there are many uncertainties in the clinical evidence, the company's economic analyses are also uncertain. The cost-effectiveness estimates are also all above the range NICE considers an acceptable use of NHS resources. So, lorlatinib is not recommended for routine use in the NHS.

Collecting more data through managed access may resolve some of the uncertainties in the clinical evidence. But, because all the cost-effectiveness estimates are above the range NICE considers an acceptable use of NHS resources, lorlatinib does not have the likely possibility to be cost effective at its current price at the end of the managed access period. So, lorlatinib cannot be recommended for use with managed access.