A regional audit of outcomes of NSCLC patients treated first line with EGFR inhibitors. Dr Jane Margetts (specialty trainee, medical oncology)

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1 A regional audit of outcomes of NSCLC patients treated first line with EGFR inhibitors Dr Jane Margetts (specialty trainee, medical oncology)

2 Rationale, brief background about EGFR, NICE guidance, questions to be answered by this audit Audit design, hospitals at which patients were treated and collaborating teams, Methods for data collection, information collected The data Conclusions what next?

3 EGFR controls cell proliferation and growth Mutations in the TK (intra cellular domains) result in signalling activation These mutations have been identified in 10% of American patients with lung cancer and up to 35% of East Asian patients (My Cancer Genome) Diagram from wikipedia They can be effectively targeted with EGFR inhibitors gefitinib and erlotinib (as reported in IPASS, OPTIMAL and EURTAC studies)

4 TKIs and lung cancer Gefitinib 1 st line: 59 dose 250mg, (funded in North East since October 2010 (NICE approved June 2010, TA 192) Erlotinib 1 st line: 9 dose 150 mg, (funded in North Easy since January 2012 (NICE approved June 2012, TA 258) Approved for the first line treatment of advanced/ metastatic EGFR mutation positive NSCC lung cancer (stage IIIb or IV)

5 Rationale for Audit EGFR inhibitors for lung cancer are reported to be highly effective (RR around 70%, significantly prolonged PFS compared with first line chemotherapy in the same population) but they are expensive and much of the data is derived from an oriental Asian population with a higher incidence of EGFR mutations and potentially different outcomes to the drug. The purpose of this audit was to examine our experience in the North East. Do we have similar mutation profiles and response rates? Given the low rates of EGFR mutations (10% or less) a region wide audit was undertaken to allow sufficient data collection for meaningful analysis.

6 Audit population: all patients in the North East with advanced EGFR mutated lung cancer treated first line with an EGFR inhibitor since the inception of treatment until mid March 2014 Caldicott approval was obtained for named data collection in Newcastle and NHS hospitals trust (applicable to any patient with a Trust Hospital number and patient information stored on the trust computer system and notes kept at NCCC). An audit tool was used to collect anonymized data from hospitals outside the trust (kindly developed by Elaine Robinson)

7 Dr Eleanor Aynsley Dr Jill Gardiner Dr Andy Hughes Dr Chris Jones Dr Louise Li Dr Talal Mansey Dr Fiona McDonald Dr Rhona McMenemin Dr Paula Mulvenna Dr Clive Peedell Mrs Elizabeth Reay Dr Tim Simmons Dr Eleanor Smith Dr Helen Turnbull Mr Steve Williamson Apologies for any omissions late at night! Data was collected by myself and Eleanor Smith as trainees within the trust involved in the patients treatment. Liz Reay from the Newcastle pharmacy kindly identified patients treated in Newcastle. In addition many consultants also identified their patients and submitted anonymised data- Thank you very much!!!

8 Hexham n=3 Wansbeck n=9 NTDGH n= 2 Freeman n=10 QE N=7 Sunderland n=5 Durham n=10 JCUH and The Friarage and Hartlepool, n=25

9 Evaluable population Data from 71 patients collected 68 evaluable 3 discounted, (1 patient declined treatement,1 patient died prior to commencing treatment,1 commenced treatment April 2014, i.e. after cut off date). Age range (Mean age 69, Median 68.5)

10 Gender: Female 39 (57%) Male 29 (43%) (All lung cancers 45% female and 54% male, cancer stats CRUK) Pathology: Adenocarcinomas = 60 (88%) Poorly differentiated Squamous cell = 2 (3%) Not otherwise specified (NOS)= 2 (3%) Bronchioalveolar = 1 (1.5%) Large cell= 1 (1.5%) Not available =2 (3%) EGFR mutations more likely if female, adenocarcinoma, oriental, non smoker

11 Smoking status at time of diagnosis: Never Smoked: 30 (44%) Ex smokers 2 50 years 19 (28%) Ex smokers? How long 3 (4%) Current smokers: 12 (18%) Not known 4 (6%)

12 EGFR mutation status 90% of patients mutations are deletions in exon 19 or L858R point mutations ( info and diagram from My Cancer Genome) In audit population= 80%.

13 Response Rates Optimal study (erlotinib in Asian population) 83% response rate (CR and PR) 96% disease control (CR/PR/SD) PFS 13.1 months EURTAC (erlotinib in European population) 64% response rate (CR and PR) PFS 9.7 months IPASS (gefitinib in Asian population) RR 71.2% Mean duration of treatment = 9.5 months (treatment ongoing for 14 patient )

14 Erlotinib versus gefitinib RR 65% Erlotinib n=9 only, 4patients still on Rx Gefitinib n= 59, data on RR from 49 available, Mean duration of treatment 9.7 months.

15 Conclusions This audit demonstrates that within the north east population: EGFR mutations are more likely in female patients, non smokers with adenocarcinoma pathology (as published) The distribution of EGFR mutations is similar to that published (80% exon 19 deletions or point mutations exon 21 codon 858) Response rates were 67% with 80% of patients achieving disease control (As per EURTAC study) There was no difference in efficacy observed with gefitinib and erlotinibnumbers for erlotinib are small.

16 This audit of first line treatment of EGFR mutated advanced NSCLC with EGFR inhibitors confirms the efficacy of this group of drugs in this setting. Crizotinib in ALK-EMl-4 mutated patients?