NICE approves lorlatinib for ALK-positive advanced NSCLC

  • Dawn O'Shea
  • Oncology drug update
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.

NICE has approved lorlatinib as an option for treating anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC) in adults whose disease has progressed after:

  • Alectinib or ceritinib as the first ALK tyrosine kinase inhibitor or
  • Crizotinib and ≥1 other ALK tyrosine kinase inhibitor.

Lorlatinib has not been compared directly with other drugs. However, indirect analyses comparing lorlatinib with platinum doublet chemotherapy (PDC) and atezolizumab with bevacizumab, carboplatin and paclitaxel (ABCP) suggest lorlatinib improves progression-free survival (PFS) and overall survival (OS). 

The main clinical evidence for lorlatinib came from study 1001, a single-arm, open-label, multicentre phase 1/2 trial, done in 13 countries but not in the UK. It comprised seven cohorts of five representing population (EXP‑2, EXP‑3A, EXP‑3B, EXP‑4, EXP‑5). The company presented evidence for the combined cohort EXP‑3B:5 (n=139), the pooled cohort of EXP‑3B, EXP‑4 and EXP‑5. EXP‑3B (n=28) had first-line treatment with alectinib or ceritinib. Cohort EXP‑4 (n=65) had previous treatment with two ALK TKIs. Cohort EXP‑5 (n=46) had ≥3 ALK TKIs. The results showed PFS of 6.9 months (95% CI 5.4-8.2) and median OS of 20.4 months (95% CI 16.1-not reached).

Because of a confidential financial arrangement with the company, the exact cost-effectiveness ratio has not been reported, but NICE said the incremental cost-effectiveness ratios (ICERs) for lorlatinib compared with PDC and ABCP were less than £50,000 per quality-adjusted life year (QALY) gained, the threshold considered to be an appropriate use of NHS resources.

The recommended dose is 100 mg lorlatinib taken orally once daily. Treatment is recommended as long as the patient is benefitting from therapy without unacceptable toxicity.