NEW YORK – The UK's National Institute for Health and Care Excellence published a guidance on Wednesday saying that it does not recommend osimertinib (AstraZeneca's Tagrisso) for untreated locally advanced or metastatic epidermal growth factor receptor-positive non-small-cell lung cancer.
In 2018, the US Food and Drug Administration approved osimertinib for the first-line treatment of patients with metastatic non-small cell lung cancer whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, the most common EGFR mutations. The approval in the EU followed shortly after. Prior to that, osimertinib was approved for patients with metastatic EGFR T790M mutation-positive NSCLC whose disease has progressed on or after an EGFR tyrosine kinase inhibitor therapy.
Locally advanced or metastatic EGFR mutation-positive NSCLC is usually first treated with afatinib (Boehringer Ingelheim's Gilotrif), erlotinib, or gefitinib, all of which have been recommended by NICE.
Evidence from a randomized controlled trial showed that treatment with osimertinib delayed disease progression by around 18.9 months compared with 10.2 months in people who are treated with erlotinib or gefitinib. However, NICE notes that there is no direct evidence comparing osimertinib with afatinib, which may be more effective than erlotinib (Astellas Pharma/Roche's Tarceva) and gefitinib (AstraZeneca's Iressa).
NICE determined that osimertinib does not meet its criteria to be considered a life-extending treatment at the end of life, and the cost-effectiveness estimates are above what NICE normally considers an acceptable use of NHS resources. Osimertinib is priced at £5,770 ($7,579) for both 80 mg and 40 mg osimertinib (pack of 30 tablets, excluding VAT; British national formulary online, accessed March 2019). NICE is also excluding osimertinib from the Cancer Drugs Fund for this reason. In the guidance, the Cancer Drugs Fund's clinical lead highlighted that follow up in the randomized trial was too short to fully capture osimertinib's beneficial effect in the brain. He also stated that osimertinib side effects benefit was also not captured in the economic model.
AstraZeneca appealed the draft guidance in July 2019, but the committee has stood by the decision not to recommend osimertinib for this indication.