Targeted therapy in lung cancer : experience of NIO-RABAT

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1 Targeted therapy in lung cancer : experience of NIO-RABAT I.ELGHISSASSI, H.ERRIHANI Medical oncology department, NIO- RABAT , FEZ

2 In Morocco, lung cancer is the most common tumor among men

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5 At the NIO : 7,5% of all types of cancer

6 FREQUENCY OF LUNG CANCER BY GENDER AT THE NIO FRQUENCY BY GENDER 14% 86% MALE FEMALE

7 FREQUENCY OF LUNG CANCER BY HISTOLOGICAL SUBTYPE AT THE NIO FREQUENCY BY HISTOLOGICAL SUBTYPE ADENOCARCINOMA 10% 17% 7% 46% SQUAMOUS CELL CARCINOMA SMALL CELL LUNG CANCER 20% OTHERS UNKOWN

8 Usually diagnosed at advanced stage

9 Same incidence in Maghreb, less than France and USA

10 Treatment : chemotherapy and targeted therapy given alone or in combinayon Targeted therapies : AnYangiogenics (bevacizumab) +++ and (EGFR- TKI) +++

11 BEVACIZUMAB IN NSCLC AT THE NIO

12 Bevacizumab in NSCLC: ECOG 4599 Study Design Eligibility: Non- squamous Non hemoptysis No CNS metastases StraVficaVon variables RT vs no RT Stage IIIB or IV vs recurrent WT loss <5% vs 5% Measurable vs non- measurable R A N D O M I S E Paclitaxel 200 mg/m 2 CarboplaVn AUC=6 q 3 weeks x 6 cycles PC x 6 cycles + Bevacizumab 15 mg/kg q 3 wks to PD Sandler A, NEJM 2006

13 ECOG 4599: Overall Survival bevacizumab + CP CP 12 mo. 24 mo. 52% 22% 44% 17% Probability HR: 0.77 (0.65, 0.93) p= Medians: 10.2, Months Sandler A, NEJM 2006

14 ECOG PC PCB p IIIB 14 % 13 % neutropenia 16,4 % 24 % bleeding 0,3 % 4,5 % < 0,01 Hypertension 0,7 % 6 % < 0,01 n tox grade CR 0 % 1,4 % PR 10 % 25,8 % ORR 10 % 27,2 % < 0,0001 PFS 4,5 mois 6,4 mois < 0,0001 MS 10,2 mois 12,5 mois 0, yr s 43,7 % 51,9 % 2-yr s 16,9 % 22,1 %

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17 OBJECTIVE OF THE STUDY to assess the toxicity and acyvity of the associayon Bevacizumab and chemotherapy as first- line treatment in payents with advanced NSCLC at the NIO

18 PATIENTS AND METHODS ProspecYve observayonal study 13 payents (NIO- RABAT) with advanced lung adenocarcinoma From january 2010 to December 2011 Toxicity was evaluated using NIH- CTC RECIST criteria were used to evaluate response to treatment

19 PATIENT CHARACTERISTICS ALL PATIENTS (n= 13) AGE (years) Median Range SEX Male Female SMOKING STATUS Current or former smoker Never smoker Unkown CHEMOTHERAPY REGIMEN Paclitaxel- CarboplaYn Gemcitabine- CDDP (85%) 2 (15%) 9 (70%) 2 (15%) 2 (15%) 9 (70%) 4 (30%)

20 SAFETY DATA ACUTE TOXICITY NO PROTEINURIA 23% 77% YES NO NO THROMBOEMBOLIC EVENTS TOXICITY TYPE NO BLEEDING 23% 31% Haematological 8% GastrointesYnal 38% Hypertension others

21 EFFICACY DATA RESPONSE TO TREATMENT 23% 31% 46% PARTIAL RESPONSE STABLE DISEASE PROGRESSIVE DISEASE

22 EFFICACY DATA PROGRESSION FREE SURVIVAL

23 EFFICACY DATA OVERALL SURVIVAL

24 Crino L. et al. Lancet Oncol, 2010 SAFETY OF BEVACIZUMAB IN PHASE IV SAIL STUDY BEVACIZUMAB IN ASSOCIATION WITH CHEMOTHERAPY WAS WELL TOLERATED IN OUR PATIENTS

25 EFFICACY OF BEVACIZUMAB IN LITERATURE 5 our study BEVACIZUMAB IN ASSOCIATION WITH CHEMOTHERAPY WAS AN ACTIVE REGIMEN IN OUR PATIENTS

26 EGFR MUTATION

27 EGFR mutayon causes conformayonal change and increased acyvayon Wild Type EGFR Mutant EGFR Ligand Extracellular domain Trans- membrane domain Tyrosine kinase domain ATP Tyrosine phosphorylavon Ras- Raf- MAPK ProliferaVon Pi3K- AKT Survival EGFR signals for longer at the cell membrane Hendricks et al 2006, Sordella et al 2004

28 EGFR mutayon and clinical criteria

29 OBJECTIVE OF THE STUDY Determine the frequency and spectrum of EGFR mutayons in an unselected group of Moroccan NSCLC payents

30 METHODS RETROSPECTIVE STUDY DATA COLLECTED FROM THE 3 LABORATORIES IN RABAT PERFORMING THE EGFR MUTATION TEST (SUBCONTRACTING) FROM NOVEMBER 2010 TO MARCH MOROCCAN PATIENTS

31 PATIENT CHARACTERISTICS ALL PATIENTS (n= 83) AGE (years) Median Range SEX Male Female HISTOLOGY Adenocarcinoma UndifferenYated carcinoma MUTATION DETECTION TECHNIQUES Gene sequencing PCR and Gene sequencing (69%) 26 (31%) 81 (97%) 2 (3%) 28 (34%) 55 (66%)

32 FREQUENCY OF EGFR MUTATION EGFR MUTATION YES :22% NO :78%

33 FREQUENCY OF EGFR MUTATION BY GENDER EGFR MUTATION IN FEMALE 58% 42% NO MUTATION MUTATION EGFR MUTATION IN MALE 5% NO MUTATION 95% MUTATION

34 EGFR mutayon and clinical criteria Our study 22% Male Female 5% 58%??? Adenocarcinoma 100%

35 The distribuyon of acyvayng mutayons among EGFR mutayon TYPE OF EGFR MUTATION 17% 11% 5% 0% 67% EXON 19 DELETION EXON 21 POINT MUTATION L858R EXON 20 EXON 18 G719 EXON 21 L861Q

36 Distribution of mutation types (% of mutations) Literature review Asian studies Non-Asian studies Our study Most prevalent mutation types Literature (n=1523) Literature (n=583) (n=18) Exon 19 deletion 51% 58% 67% Exon 21 point mutation L858R 42% 32% 17% Exon 20 2% 6% 11% Exon 18 G719A/C 3% 2% 5% Exon 21 L861Q 1% 1% 0% AstraZeneca Data on File 2009

37 AT THE NIO- RABAT Five payents received EGFR- TKI OR = 1OO%

38 THANK YOU FOR YOUR ATTENTION