The Scottish Medicines Consortium (SMC) has approved osimertinib (Tagrisso, AstraZeneca) for adults with locally advanced, unresectable stage III non-small cell lung cancer (NSCLC) whose tumours harbour epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 substitution mutations and who have not had disease progression after platinum-based chemoradiation therapy. 

The decision, which requires implementation through an approved Patient Access Scheme, provides a new treatment option for patients who are ineligible for durvalumab, a PD-L1 inhibitor previously approved for similar indications.

EGFR-Mutant Lung Cancer

NSCLC accounts for approximately 80% of lung cancers. Stage III tumours are a heterogeneous group in which 60%-90% are unresectable at diagnosis. EGFR mutations occur in about 20%-30% of White patients and around 50% of Asian patients, appearing more frequently in women, never-smokers, and patients with adenocarcinoma. Approximately 85%-90% of EGFR mutations involve exon 19 deletions or exon 21 substitutions.

Osimertinib is the first EGFR tyrosine kinase inhibitor licensed for patients with unresectable stage III NSCLC and EGFR mutations who remain progression-free after standard chemoradiation therapy. The drug targets EGFRs carrying sensitising mutations and the resistance mutation T790M, leading to cancer cell death.

Current treatment guidelines recommend concurrent chemoradiation therapy for unresectable stage III NSCLC, followed by osimertinib as consolidation therapy in patients with EGFR-mutated disease who do not experience progression.

Survival Data

The approval was based on the phase 3 LAURA study, which showed significant improvements in progression-free survival. 

The study enrolled 216 patients aged 18 years or older with unresectable stage III NSCLC and EGFR mutations who remained progression-free after chemoradiation therapy. Patients received either osimertinib 80 mg daily or placebo in a 2:1 ratio within 6 weeks of completing chemoradiation.

At the primary analysis with median follow-up of 22 months, osimertinib achieved a median progression-free survival (PFS) of 39.1 months compared with 5.6 months for placebo (hazard ratio 0.16). Three-year PFS rates reached 58% with osimertinib vs 10% with placebo. The objective response rate was 57% with osimertinib compared with 33% with placebo.

Safety Considerations

Osimertinib showed a toxicity profile consistent with its known characteristics. Radiation pneumonitis occurred at higher rates with osimertinib than with placebo (48% vs 38%). Common adverse events included diarrhoea, rash, and decreased appetite. Treatment-related serious adverse events occurred in 8.4% of osimertinib recipients vs 1.4% of placebo recipients.

The recommended dose is 80 mg orally once daily until disease progression or unacceptable toxicity occurs.

Implementation

Clinical experts consulted by the SMC considered that osimertinib addresses an unmet need for patients who are not eligible to receive durvalumab. 

The introduction of osimertinib in this setting is expected to have minimal service impact, as existing systems already manage its use in other indications. The company estimated that 13 patients would be eligible for treatment in year 1, increasing to 41 patients by year three, with uptake rates projected at 22% initially and 84% by the third year.