Lorlatinib for untreated ALK-positive advanced non-small-cell lung cancer (Review of TA909) (ID6434)

Lung cancer falls into two main histological categories: around 80 to 85% are nonsmall-cell lung cancers (NSCLC) and the remainder are small cell lung cancers(1). NSCLC can be further classified into squamous cell carcinoma and non-squamous cell carcinoma.

Approximately 70% of NSCLC are of non-squamous histology and can be either large-cell undifferentiated carcinoma or adenocarcinoma(2).

Most lung cancers are diagnosed at an advanced stage when the cancer has spread to lymph nodes and other organs in the chest (locally advanced disease; stage 3) or to other parts of the body (metastatic disease; stage 4).In 2022 90% (around 33200) of people diagnosed with lung cancer in England and Wales had NSCLC(3).

Of these people 50% had stage 4 disease(3).

Lung cancer caused approximately 35000 deaths in the UK between 2017-2019(4). 48% of people with lung cancer survive for more than 1-year after diagnosis(3). It is estimated that around 2 to 6% of NSCLCs have an ALK fusion genetic alteration. This alteration inhibits processes which stop lung cells dividing and can lead to cancer(567).

ALK fusions can occur in any type of NSCLC but are most likely to occur in adenocarcinoma histology.(6) The treatment pathway for NSCLC can be divided into interconnected decision points based on the number staging system and line of therapy.

Treatment choices are influenced by the presence of biological markers (including programmed cell death 1 ligand PD-L1 status) oncogenic driver genetic alterations histology (squamous or non-squamous) and previous treatment.

NICE’s Technology Appraisal Pathway Pilot scope for treatments for non-small-cell lung cancer outlines in more detail the NSCLC treatment pathway.For the majority of people with NSCLC the aims of treatment are to prolong survival and improve quality of life.

For people with ALK-positive advanced NSCLC first line treatment options include crizotinib (TA406) ceritinib (TA500) alectinib (TA536) and brigatinib (TA670). People with NSCLC of an unknown ALK status may be offered initial treatment with platinum-doublet chemotherapy. Lorlatinib received a negative recommendation in TA909 evaluating lorlatinib for untreated ALK-positive advanced NSCLC.

Based on the review of TA909 this scope is a review of TA909 and focuses on the additional evidence collected from the CROWN trial.

It is expected that the additional evidence will address the uncertainties in TA909 after which NICE will decide whether or not to recommend lorlatinib for routine use in the NHS.References:1. Types of lung cancer. Cancer Research UK. Accessed July 2024.2.

Howlader N Noone AM Krapcho M Miller D Brest A Yu M Ruhl J Tatalovich Z Mariotto A Lewis DR Chen HS Feuer EJ Cronin KA (eds).

SEER Cancer Statistics Review 1975-2016 National Cancer Institute. [Available from: https://seer.cancer.gov/csr/1975_2016/ ]. Accessed July 2024.3. NLCA annual report 2024 (2022 data) National Lung Cancer Audit. Accessed July 2024.4. Lung cancer mortality statistics (2022). Cancer Research UK. Accessed July 2024.5.

Cancer Research UK (2023) Targeted and immunotherapy treatment for lung cancer. Accessed July 2024.