Targeted therapy in lung cancer : experience of NIO-RABAT I.ELGHISSASSI, H.ERRIHANI Medical oncology department, NIO- RABAT 02-05- 2012, FEZ
In Morocco, lung cancer is the most common tumor among men
At the NIO : 7,5% of all types of cancer
FREQUENCY OF LUNG CANCER BY GENDER AT THE NIO FRQUENCY BY GENDER 14% 86% MALE FEMALE
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
Usually diagnosed at advanced stage
Same incidence in Maghreb, less than France and USA
Treatment : chemotherapy and targeted therapy given alone or in combinayon Targeted therapies : AnYangiogenics (bevacizumab) +++ and (EGFR- TKI) +++
BEVACIZUMAB IN NSCLC AT THE NIO
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
ECOG 4599: Overall Survival 1.0 0.8 bevacizumab + CP CP 12 mo. 24 mo. 52% 22% 44% 17% Probability 0.6 0.4 0.2 HR: 0.77 (0.65, 0.93) p= 0.007 Medians: 10.2, 12.5 0 0 6 12 18 24 30 36 Months Sandler A, NEJM 2006
ECOG- 4599 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 5 2 9 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 0,0075 1-yr s 43,7 % 51,9 % 2-yr s 16,9 % 22,1 %
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
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
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 63 49-78 11 (85%) 2 (15%) 9 (70%) 2 (15%) 2 (15%) 9 (70%) 4 (30%)
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
EFFICACY DATA RESPONSE TO TREATMENT 23% 31% 46% PARTIAL RESPONSE STABLE DISEASE PROGRESSIVE DISEASE
EFFICACY DATA PROGRESSION FREE SURVIVAL
EFFICACY DATA OVERALL SURVIVAL
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
EFFICACY OF BEVACIZUMAB IN LITERATURE 5 our study BEVACIZUMAB IN ASSOCIATION WITH CHEMOTHERAPY WAS AN ACTIVE REGIMEN IN OUR PATIENTS
EGFR MUTATION
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
EGFR mutayon and clinical criteria
OBJECTIVE OF THE STUDY Determine the frequency and spectrum of EGFR mutayons in an unselected group of Moroccan NSCLC payents
METHODS RETROSPECTIVE STUDY DATA COLLECTED FROM THE 3 LABORATORIES IN RABAT PERFORMING THE EGFR MUTATION TEST (SUBCONTRACTING) FROM NOVEMBER 2010 TO MARCH 2012 83 MOROCCAN PATIENTS
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 61 37-84 57 (69%) 26 (31%) 81 (97%) 2 (3%) 28 (34%) 55 (66%)
FREQUENCY OF EGFR MUTATION EGFR MUTATION YES :22% NO :78%
FREQUENCY OF EGFR MUTATION BY GENDER EGFR MUTATION IN FEMALE 58% 42% NO MUTATION MUTATION EGFR MUTATION IN MALE 5% NO MUTATION 95% MUTATION
EGFR mutayon and clinical criteria Our study 22% Male Female 5% 58%??? Adenocarcinoma 100%
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
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
AT THE NIO- RABAT Five payents received EGFR- TKI OR = 1OO%
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