The following aims to estimate the expected usage of the NICE positively appraised medicines afatinib, dacomitinib, erlotinib, gefitinib and osimertinib, in people with epidermal growth factor receptor (EGFR) positive stage 3b and stage 4 advanced non-small-cell lung cancer (NSCLC), first-line treatment with osimertinib in people with stage Ib to stage IIIa EGFR positive NSCLC and second line use of osimertinib in people who are T790 mutation positive EGFR positive NSCLC.
Where these medicines have a licenced indication not positively appraised by NICE, usage has not been estimated. While this usage is expected to be small it may result in a lower expected usage when compared to observed usage.
1. Incidence of lung cancer
The SmPC states that these medicines are indicated in an adult population only.
Estimated incidence of lung cancer in adults aged 20 years or older was reported by the National Lung Cancer audit (2022) for the year 2020 in England.
|
Point estimate
|
Reference
|
Newly diagnosed lung cancers (C34 Malignant neoplasm of bronchus and lung)
|
31,371
|
(1)
|
2. Estimated number of people with non-small-cell lung cancer
The proportion of new cases of lung cancer that are non-small-cell lung cancer (NSCLC) is reported in the national lung cancer audit (2022) to be 72.2%. This proportion has been used to inform the upper and lower range and applied to the point estimate calculated in step 1.
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
Estimated number of people with non-small-cell lung cancer in England
|
22,650
|
22.650
|
22,650
|
(1)
|
3. Proportion of people presenting with stage IIIb (advanced) and stage IV (metastatic) NSCLC
The proportion of new cases of NSCLC that are diagnosed stage IIIb (advanced), or stage IV (metastatic) is reported in the national lung cancer audit as 55%. This figure has been used to inform the upper and lower range. This proportion has been applied to the point estimate calculated in step 2.
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
Estimated number of people presenting with stage IIIb or stage IV NSCLC
|
12,458
|
|
|
(1)
|
4. Proportion of people successfully assessed for EGFR
The spotlight audit on molecular testing in advanced lung cancer (2020), shows for EGFR, 92% or 92,000 per 100,000 of people with advanced lung adenocarcinoma were assessed. The 95% confidence interval around the reported prevalence (95% CI 91,613 to 92,375) has been calculated using the exact binomial method (Pezzullo 2009).
The prevalence and confidence interval has been applied to the adult population calculated in step 3.
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
Estimated number of people successfully assessed for EGFR.
|
11,461
|
11,413
|
11,508
|
(2,3,9)
|
The spotlight audit on molecular testing in advanced lung cancer (2020), shows, for EGFR, 8% of people with advanced lung adenocarcinoma were not assessed and have unidentified EGFR status. Patients in whom the disease has progressed after non-targeted chemotherapy may have erlotinib if their patient characteristics suggest that their tumour may be EGFR mutation positive. An element of clinical judgement is needed when identifying these patients and are not calculated here.
5. Proportion of people where molecular testing was successful
The spotlight audit on molecular testing in advanced lung cancer (2020), shows, for EGFR, 97.7% or 97,700 per 100,000 of people, molecular testing was successful, giving a positive or negative result. The 95% confidence interval around the reported proportion (95% CI 97,469 to 97,911) has been calculated using the exact binomial method (Pezzullo 2009).
The proportion and confidence interval has been applied to the adult population calculated in step 4.
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
Estimated number of people successfully assessed for EGFR.
|
11,197
|
11,124
|
11,268
|
(2,3)
|
6. Proportion of people who test positive for EGFR mutation
The spotlight audit on molecular testing in advanced lung cancer (2020), reported 10% or 10,000 per 100,000 have the EGFR mutation present. The 95% confidence interval around the reported prevalence (95% CI 9,562 to 10,451) has been calculated using the exact binomial method (Pezzullo 2009).
The reported proportion and confidence interval has been applied to the upper and lower range and the point estimate for people successfully assessed, calculated in step 5.
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
Estimated number of people expected to have a positive EGFR mutation status
|
1,120
|
1,064
|
1,178
|
(2,3)
|
7. Proportion of people who receive first line afatinib, dacomitinib, erlotinib, gefitinib or osimertinib
The spotlight audit on molecular testing in advanced lung cancer (2020), 75% of patients with an EGFR mutation received a first-line tyrosine kinase inhibitor.
The reported proportion has been applied to the upper and lower range and the point estimate who tested EGFR mutation positive calculated in step 6.
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
Estimated number of people who receive afatinib, dacomitinib, erlotinib, gefitinib or osimertinib
|
840
|
798
|
884
|
(2,3)
|
8. Proportion of people who progress following first line treatment with afatinib, dacomitinib, erlotinib or gefitinib (previously treated EGFR-positive)
The RIA for TA654 (2020) states that in year 1, 20% of first line treatment will be with osimertinib. Of the remaining 80% who received first-line treatment with afatinib, dacomitinib, erlotinib or gefitinib, the disease will progress in 65% of cases (TA416 2016) and will then be eligible for osimertinib. These proportions (80% and 65%) have been applied as a scaling factor to the point estimate and the lower and upper range summed in step 7.
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
Estimated number of people who progress following first line treatment
|
437
|
415
|
460
|
(4,5)
|
9. Proportion of people who harbour T790M mutation at progression (previously treated EGFR-population)
Based on genomic analysis, progression on a first-line EGFR TKI is characterised by an acquired secondary EGFR kinase domain mutation labelled T790M, causing resistance to the first-line EGFR TKI. The proportion of people who harbour T790M mutation at progression is reported in Mazza (2017) to be between 50% and 60%. The midpoint (55%) has been applied to the point estimate and the proportions (50% and 60%) applied to the upper and lower range calculated in step 8.
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
Estimated number of people who harbour T790M mutation at progression and eligible for osimertinib
|
240
|
208
|
276
|
(6,10)
|
10a. Proportion of people with stage Ib to IIIa NSCLC
The NICE technology appraisal TA761 published in January 2022 and recommended an additional population of people eligible to receive Osimertinib for stage Ib to IIIa NSCLC who had tumour resection surgery.
The number of people with stage Ib to IIIa NSCLC is reported in the national lung cancer audit 2022 as 25.5%. This figure has been used to inform the upper and lower range. This proportion has been applied to the point estimate calculated in step 2
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
Estimated number of people with stage Ib to IIIa NSCLC |
5,776
|
5,776
|
5,776
|
(7,1)
|
10b. Proportion of people with NSCLC who had tumour resection surgery
The national lung cancer audit 2022 reports the number of people with NSCLC who had tumour resection surgery as 20%. This figure has been used to inform the upper and lower range. This proportion has been applied to the point estimate calculated in step 10a.
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
Estimated number of people with NSCLC who had tumour resection surgery
|
4,530
|
4,530
|
4,530
|
(1)
|
10c. Proportion of people with NSCLC who had tumour resection surgery and were EGFR positive
The spotlight audit on molecular testing in advanced lung cancer (2020), reported 10% or 10,000 per 100,000 have the EGFR mutation present. The reported proportion and confidence interval has been applied to the upper and lower range and the point estimate for people who had tumour resection surgery, calculated in step 10b.
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
Estimated number of people with NSCLC who had tumour resection surgery and were EGFR positive
|
453
|
453
|
453
|
(2)
|
10d. Proportion of people with NSCLC who had tumour resection surgery and were EGFR positive with exon 19 deletions or exon 21 L858R mutations
Based on data reviewed in Zhang (2016), it is estimated that 90% of people who are EGFR positive have exon 19 deletions or exon 21 L858R mutations. This has been applied to the upper and lower range and the point estimate for people who had tumour resection surgery and were EGFR positive, calculated in step 10c.
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
Estimated number of people with NSCLC who had tumour resection surgery and were EGFR positive with exon 19 deletions or exon 21 L858R mutations
|
408
|
408
|
408
|
(8)
|
11a. Treatment population for afatinib, dacomitinib, erlotinib, gefitinib and osimertinib
The total treatment population for first line afatinib, dacomitinib, erlotinib, gefitinib or osimertinib has been taken from step 7 and step 10d and added to the treatment population for second line osimertinib, step 9.
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
Estimated treatment population first line afatinib, dacomitinib, erlotinib, gefitinib and first or second line osimertinib
|
1,488
|
1,414
|
1,568
|
(-)
|
11b. Calculate estimated usage volume – first line afatinib, dacomitinib, erlotinib, gefitinib and first or second line osimertinib
The estimated treatment population has been used to calculate an expected annual volume of medicine per year in Actual Daily Doses (ADD).
11c. Calculate estimated usage volume – afatinib, erlotinib and gefitinib
The total estimated treatment population for first line afatinib, erlotinib, gefitinib has been taken from step 7. It has been assumed that treatment will be for 12 months, and usage will be spread evenly.
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
Estimated treatment population first line afatinib, dacomitinib, erlotinib, gefitinib and first or second line osimertinib
|
504
|
479
|
530
|
(-)
|
Estimated median progression-free survival (days)
|
365
|
365
|
365
|
(4,11)
|
Total estimated annual usage (ADDs)
|
183,960
|
174,762
|
193,596
|
|
11d. Calculate estimated usage volume – dacomitinib
The total estimated treatment population for dacomitinib has been taken from step 7. It has been assumed that treatment will be for 12 months and usage will be spread evenly.
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
Estimated treatment population dacomitinib
|
168
|
160
|
177
|
(-)
|
Estimated median progression-free survival (days)
|
365
|
365
|
365
|
(4,11)
|
Total estimated annual usage (ADDs)
|
61,320
|
58,254
|
64,532
|
|
11e. Calculate estimated usage volume – first and second line osimertinib
The total estimated treatment population for first line osimertinib has been taken from step 7 and step 10d. It has been assumed that treatment will be for 21 months (639 days) and usage will be spread evenly. Second line osimertinib is taken from step 9.
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
Estimated treatment population first or second line osimertinib
|
816
|
776
|
861
|
(-)
|
Estimated median progression-free survival (days)
|
639
|
639
|
639
|
(4,11)
|
Total estimated annual usage (ADDs)
|
521,424
|
495,608
|
550,051
|
|
11f. Total treatment volume – afatinib, dacomitinib, erlotinib, gefitinib and first or second line osimertinib
The total treatment volume (ADD) for afatinib, dacomitinib, erlotinib, gefitinib and first or second line osimertinib has been summed from steps 11c, 11d and 11e.
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
Estimated treatment population first line afatinib, dacomitinib, erlotinib, gefitinib and first or second line osimertinib
|
766,704
|
728,624
|
808,179
|
(-)
|
12. Estimated usage by quarter per 100,000 population
Estimated annual ADD usage was divided by 4 to show quarterly ADD usage. This was then divided by the whole England population and multiplied by 100,000 to give an estimated usage per 100,000 population. This has been applied to the point estimate and upper and lower range calculated in step 11f.
|
Point estimate
|
Lower range
|
Upper range
|
Reference
|
ADD per 100,000 population England
|
339
|
322
|
357
|
(-)
|
References
- Royal College of Physicians. National Lung Cancer Audit (2022) Newly diagnosed lung cancers 2020, England. London: RCP, 2022.Available from: NLCA [Accessed: 28/06/2022]
- Spotlight audit on molecular testing in advanced lung cancer (2020). Available from https://www.rcplondon.ac.uk/projects/outputs/spotlight-audit-molecular-testing-advanced-lung-cancer-2019-diagnoses-2017[accessed 08/11/2021]
- Pezzullo. (2009) Exact Binomial and Poisson Confidence Intervals calculator. Available from http://statpages.org/confint.html [Accessed 09/11/2021].
- TA654 (NICE 2020). Osimertinib for untreated EGFR mutation-positive non-small-cell lung cancer. Available from https://www.nice.org.uk/guidance/ta654 [Accessed 02/11/2021]
- TA416 (NICE 2016). Manufacturers submission (AstraZeneca 2016) Available from https://www.nice.org.uk/guidance/ta416/evidence [Accessed 29/01/2018]
- Mazza V, Cappuzzo F. Treating EGFR mutation resistance in non-small cell lung cancer – role of osimertinib. The Application of Clinical Genetics. 2017; 10:49-56. doi:10.2147/TACG.S103471.
- TA761 (NICE 2022). Osimertinib for adjuvant treatment of EGFR mutation-positive non-small-cell lung cancer after complete tumour resection. Available from https://www.nice.org.uk/guidance/ta761 [Accessed 28/06/2022]
- Zhang et al (2016). The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016 Nov 29; 7(48): 78985–78993.
- TA374 (2015) Erlotinib and gefitinib for treating non-small-cell lung cancer that has progressed after prior chemotherapy. Final appraisal determination, section 4.3.6. Available from https://www.nice.org.uk/guidance/ta374 [accessed 29/01/2018]
- Cappuzzo F, Ciuleanu T, Stelmakh L (2010). Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. The Lancet Oncology. Volume 11, Issue 6, June 2010, page 521-529
- Datapharm Communications Limited (2017) The Electronic Medicines Compendium [WWW]. Available from: http://www.medicines.org.uk/emc/, [Accessed: 10/11/2021]