1. Network Experience of TKI inhibitors as 1 st line use in advanced NSCLC Dr Jill Gardiner and Mr Steve Williamson April 2012

2. Plans for Iressa Audit Preliminary data only from Astra Zeneca. No information on toxicity and QL. Numbers for each trust are small so all of the region needs to be included in the audit to produce meaningful data. Centralisation of Consent/Caldecott via the Network will allow much easier access of patient information across the region.

3. Iressa Audit Cover period 2010 and 2011 Response rates Duration of treatment Toxicity Response to 2 nd line treatment Overall survival

4. Tarceva

5. A standard second line treatment for Advanced NSCLC in the region. Data is now available in the first line setting for mutation positive advanced NSCLC. Tarceva has a licence as a first line treatment for mutation positive advanced NSCLC. It is at least comparable with the Iressa data. It has the advantage of Phase 3 data in the European population – the EURTAC study

6. Data Summary RR TKI v chemoPFS TKI v chemo Asian Iressa IPASS ( Mok et al NEJM 361 p947 2009) 71.2% v 47.3%9.5m v 6.3m Asian Tarceva OPTIMAL ( Zhou et al Lancet Oncology 12 p 735 2011) 83% v 36%13.1m v 4.6m European Tarceva EURTAC ( Rossell et al ASCO 2011 #7503) 58% v 15%9.4m v 5.2m

7. Primary endpoint: PFS in ITT population (interim analysis 2 Aug 2010) PFS probability 1.0 0.8 0.6 0.4 0.2 0 Erlotinib (n=77) Chemotherapy (n=76) HR=0.42 (0.27–0.64) Log-rank p<0.0001 Time (months) 0369121518212427 Patients at risk Erlotinib 7753422617117520 Chemo7640147532100 9.4 5.2 IRC-assessed PFS confirmed these results

8. Best overall response in ITT population Erlotinib (n=77) n (%) Chemotherapy (n=76) n (%) Erlotinib (n=86) n (%) Chemotherapy (n=87) n (%) Complete response2 (3)0 (0)2 (2)0 (0) Partial response40 (52) 8 (11)48 (56) 13 (15) Objective response rate42 (55) 8 (11)50 (58) 13 (15) Stable disease18 (23)42 (55)18 (21)44 (51) Disease control rate60 (78)50 (66)68 (79)57 (66) Progressive disease6 (8)10 (13)6 (7)11 (13) No response assessment11 (14)16 (21)12 (14)19 (22) Interim analysis (Aug 2, 2010) Updated analysis (Jan 26, 2011)

9. Conclusions EURTAC is the first prospective study of an EGFR tyrosine-kinase inhibitor (TKI) versus chemotherapy for first-line treatment of EGFR mutation-positive NSCLC in Caucasian patients The study results confirms significant benefit in PFS of erlotinib over standard chemotherapy – 63% reduction in risk of progression (HR=0.37) OS data are immature, with high level of known crossover As expected, no new safety findings – tolerability of erlotinib was consistent with previous studies Erlotinib provides significant benefits over first-line chemotherapy in EGFR mutation-positive disease

10. Tarceva as first line treatment for Mutation positive NSCLC Approved by SMC Jan 2012 Approved by NECDAG Jan 2012 Due for NICE review June 2012

11. Tarceva Will everyone switch to Tarceva or will some continue to use Iressa? The plan is to audit the data we obtain. May allow us to do a comparison with the Iressa data.