The National Institute for Health and Care Excellence (NICE) published an Appraisal Consultation Document (ACD) for osimertinib (marketed as Tagrisso), a medicine recognised internationally and in the UK as an effective medicine for a subset of patients with non-small cell lung cancer (NSCLC).

The preliminary recommendation from NICE is to not recommend osimertinib for adult patients with locally advanced or metastatic NSCLC, whose tumour harbours the epidermal growth factor receptor (EGFR) and T790M mutations.

The committee also concluded that, at this stage, osimertinib does not meet the criteria to be considered for inclusion in the Cancer Drug Fund (CDF).

The UK lags behind other European countries in lung cancer survival rates, with a five-year survival rate of 9% versus an average 13% in Europe.¹

Every year in the UK, approximately 39,000 people are diagnosed with lung cancer, and about 87% of these cases are NSCLC.^{2, 3}

Ten percent of people with NSCLC will have tumours harbouring EGFR mutations.⁴

Most patients with EGFR NSCLC develop resistance to first line targeted therapies (EGFRm tyrosine kinase inhibitors) because of a secondary mutation called T790M.⁵

Osimertinib is the first targeted treatment for this group of patients, whose only other treatment option is cytotoxic chemotherapy.

With current standard chemotherapy, patients who have progressed after first line treatment have an average life expectancy of approximately one year.

Osimertinib was given accelerated assessment by the European Medicines Agency (EMA), which allows marketing authorisation for medicines based on early clinical data because of the major therapeutic advantage and patient benefits they may offer over existing treatments.

Osimertinib was granted expedited conditional marketing authorisation by the European Commission (EC) on 2nd February 2016.

In addition, in December 2015, osimertinib was the fourth medicine to be accepted onto the UK Government’s Early Access to Medicines Scheme (EAMS).

In the ACD published by NICE, the committee concluded that, at this time, osimertinib cannot be considered to have met one of the criterion used for end-of-life consideration because data on overall survival benefit are currently too immature.

While AstraZeneca was able to estimate what the overall survival data could show over a longer period of time using established health economic models, the NICE committee considered this to be associated with a large degree of uncertainty.

The committee therefore determined that until further data confirming a survival benefit are available, the standard NICE cost-effectiveness threshold of £30,000 per quality-adjusted life year (QALY) should be used rather than the £50,000/QALY threshold considered appropriate for end-of-life medicines.

The AstraZeneca submission to NICE showed an ICER of just under £43,000 per QALY for osimertinib, which is within the threshold for end-of-life medicines, but higher than the standard threshold.

Studies show osimertinib has the potential to extend quantity and improve quality of life. 

The latest pooled results from the AURA Phase II studies in 411 pre-treated patients with EGFR T790M mutation-positive NSCLC treated with osimertinib 80mg showed a median progression-free survival of 11 months (95% CI: 9.6-12.4 months) and an objective response rate (a measurement of tumour shrinkage) of 66% (95% CI: 61%-71%).

The most common adverse events were generally mild to moderate.⁶

AstraZeneca will submit additional analyses and updated data on osimertinib as part of the ACD consultation process, which closes on 14th July.

References

1. De Angelis R, Sant M, Coleman MP, Francisci S et al. Cancer Survival in Europe 1999-2007by country and age: results of EUROCARE-5-a population based study. Lancet Oncology 2014;15:23-43

2. Macmillan. Risk factors and causes of lung cancer. Available at: http://www.nhs.uk/ipgmedia/national/Macmillan Cancer Support/Assets/Riskfactorsandcausesoflungcancer(MCS5Pages).pdf Last accessed June 2016.

3. Cancer Research UK. Types of lung cancer. Available at: http://www.cancerresearchuk.org/about-cancer/type/lung-cancer/about/types-of-lung-cancer Last accessed June 2016.

4. Barlesi F, Blons H, Beau-Faller M, Rouquette I, Ouafik L, Mosser J, et al.  Biomarkers (BM) France: Results of routine EGFR, HER2, KRAS, BRAF, PI3KCA mutations detection and EML4-ALK gene fusion assessment on the first 10,000 non-small cell lung cancer (NSCLC) patients (pts). J Clin Oncol 2013;31 ([Suppl; abstr 8000]).

5. Yu HA, et al. Analysis of Tumour Specimens at the Time of Acquired Resistance to EGFR-TKI Therapy in 155 Patients with EGFR-Mutant Lung Cancer. Clin Cancer Research:2013:19(8):2240-2246.

6. Yang JCH, et al.  Osimertinib (AZD9291) in pre-treated patients with T790M-positive advanced NSCLC: updated Phase I and pooled Phase II results. Abstract LBA2_PR [Oral Presentation]. Presented at the European Lung Cancer Conference, 13-16 April 2016, Geneva, Switzerland.

7. AstraZeneca PLC. TAGRISSO™ (osimertinib) approved in EU as first-in-class treatment for patients with EGFR T790M mutation-positive metastatic non-small cell lung cancer. Issued on February 3rd 2016. Available at: https://www.astrazeneca.com/media-centre/press-releases/2016/tagrisso-osimertinib-approved-in-eu-as-first-in-class-treatment-for-lung-cancer-03022016.html. Last accessed June 2016.

8. National Institutes of Health. AZD9291 Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (AURA3). Available at: https://clinicaltrials.gov/ct2/show/NCT02151981?term=AURA3&rank=1. Last accessed June 2016.

9. National Institutes of Health. AZD9291 Versus Placebo in Patients With Stage IB-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy (ADAURA). Available at: https://www.clinicaltrials.gov/ct2/show/NCT02511106?term=AZD9291 Versus Placebo in Patients&rank=1. Last accessed June 2016.

10. National Institutes of Health. AZD9291 Versus Gefitinib or Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (FLAURA). Available at https://clinicaltrials.gov/ct2/show/NCT02296125?term=FLAURA&rank=1. Last accessed June 2016.

11. National Institutes of Health. Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors, AZD3759 or AZD9291, in Patients Who Have Advanced Non-Small Cell Lung Cancer (BLOOM). Available at: https://clinicaltrials.gov/ct2/show/NCT02228369?term=AZD9291 brain met&rank=1. Last acccessed June2016.

12. National Institutes of Health. Study of AZD9291 Plus MEDI4736 Versus AZD9291 Monotherapy in NSCLC After Previous EGFR TKI Therapy in T790M Mutation Positive Tumours (CAURAL). Available at https://clinicaltrials.gov/ct2/show/NCT02454933?term=CAURAL&rank=1. Last accessed June 2016.

13. National Institutes of Health. AZD9291 in Combination With Ascending Doses of Novel Therapeutics. Available at: https://clinicaltrials.gov/ct2/show/NCT02143466?term=azd9291&rank=1. Last accessed June 2016.

Source: AstraZeneca