Management des patients atteints de cancer bronchique triple négatif
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1 Management des patients atteints de cancer bronchique triple négatif Réunion de formation du GFPC Paris, 12 Décembre 2013 Fabrice BARLESI, MD, PhD Multidisciplinary Oncology & Therapeutic Innovations INSERM U911 CRO2 Marseille France
2 Conflits d intérêts I provided consultations and attended advisory boards for Astra Zeneca, Boehringer Ingelheim, Daichii Saiko, Eli Lilly Oncology, F. Hoffmann La Roche Ltd, Glaxo Smithkline, Novartis, and Pfizer, for which I received appropriate honoraria.
3 Agenda Définition & rationnel Standard actuel 1 ère ligne et maintenance 2 ème ligne et au-delà Perspectives Priorités Soins de support
4 Agenda Définition & rationnel Standard actuel 1 ère ligne et maintenance 2 ème ligne et au delà Perspectives Priorités Soins de support
5 Définition Patients dont la tumeur n est pas : EGFR mutée ALK transloquée KRAS mutée
6 Triples négatifs : épidémiologie EGFR act mut 9.5% EGFR res mut 0.8% HER2 mut 0.9% UKN/Other 53.8% KRAS mut 27% N #10,000 ALK rearrangement 3.7% BRAF mut 1.7% PI3K mut 2.6% Barlesi F et al, ASCO 2013 #8000
7 Triples négatifs: épidémiologie Smokers Never smokers EGFR activ EGFR resist KRAS BRAF ALK PI3K HER2 UNK Barlesi F et al, ASCO 2013 #8000
8 Triples négatifs: épidémiologie Squamous Cell Carcinoma Li et al, J Clin Oncol 2013; Sos ML et al, Oncogene 2012
9 Rationnel: EGFR mut. Etudes Pop. Médicament EGFR RO % Mut + (N) TKI vs CT IPASS Asie Gefitinib ,2 vs 47,3 First-SIGNAL Asie Gefitinib 42 84,6 vs 37,5 WJTOG 3405 Asie Gefitinib ,1 vs 32,2 NEJGSG002 Asie Gefitinib ,5 vs 29 OPTIMAL Asie Erlotinib vs 36 EURTAC Europe Erlotinib vs 11 LUX LUNG 3 Mixte Afatinib vs 22.6 LUX LUNG 6 Asie Afatinib vs 23 SSP (HR, IC95%) 0,48 (0,36-0,64) 0,61 (0,31 1,22) 0,49 (0,34 0,71) 0,30 (0,22 0,42) 0,16 (0,10 0,26) 0,42 (0,27-0,64) 0.58 ( ) 0.28 ( )
10 Rationnel: EML4-ALK transloc. Probability of survival without progression (%) Crizotinib (n=172 a ) Pemetrexed (n=99 a ) Docetaxel (n=72 a ) Events, n (%) 100 (58) 72 (73) 54 (75) Median, mo HR b (95% CI) 0.59 (0.43 to 0.80) 0.30 (0.21 to 0.43) P < PhIII 1st line completed Results awaited Time (months) Shaw A et al, NEJM 2013
11 Rationnel: KRASmut. 1,0 1,0 0,8 0,8 0,6 0,6 0,4 0,4 KRAS sauvage 0,2 0 Patients à risque KRAS WT KRAS muté KRAS sauvage Mois 7 7 KRAS muté ,2 0 Patients à risque KRAS WT KRAS muté Mois KRAS muté KRAS muté KRAS sauvage KRAS muté KRAS sauvage SSP médiane (mois) 4,9 6,0 SG médiane (mois) 10,3 13,2 HR (IC 95 ) = 1,06 (0,71-1,57) ; p = 0,79 HR (IC 95 ) = 1,22 (0,77-1,94) ; p = 0,40 Macerelli et al, ESMO 2013
12 Rationnel: KRASmut. Test interaction for OS by KRAS, p=0.09 Zhu C et al, J Clin Oncol 2008
13 Rationnel: KRASmut. Meta-analysis KRAS (%) Probability of PFS OS response (HR) Linardou et al 17 trials 165/1005 (16.4) 0.28 No data Mao et al 22 trials 231/1470 (15.7) 0.29 No data Linardou H et al, Lancet Oncol 2008; Mao C et al, Lung Cancer 2010
14 Rationnel: stratégie thérapeutique PS0 Stage IV patient 1L Standard CDDPbased Cx 2L Standard 2 nd line Cx 3L Standard 3 rd line Cx Standard bioguided Rx EGFRm ALK Experiment. EGFR or ALK Bioguided Rx (rebiopsy)
15 Rationnel / cancer du sein Cancer du sein Cancer bronchique non à petites cellules RE - Pas d hormonothérapie EGFR non muté Pas d EGFR-TKI 1 ère ligne RP - ALK non transloqué Pas de crizotinib 2 ème ligne (1 ère ligne) HER2 non amplifié Pas de HER2 inhibiteur KRAS muté Pas d EGFR-TKI en 2 ème /3 ème ligne (?) Métastases (poumon, cerveau) Pronostic péjoratif? Biomarqueurs France!
16 The biomarqueurs France project Nationwide biomarkers assessment Reality of bioguided treatments? Efficacy? Supported by Sponsored by
17 Agenda Définition & rationnel Standard actuel 1 ère ligne et maintenance 2 ème ligne et au delà Perspectives Priorités Soins de support
18 Raisonnement: stratégie thérapeutique Pao W, Nat Rev Cancers 2010
19 Raisonnement: stratégie thérapeutique Traitements avec la meilleure s. globale? Autres drivers oncogéniques activables? Stratégies de combinaisons séquentielles?
20 Raisonnement: combo? Schiller J, NEJM 2002
21 Raisonnement: Pemetrexed? Scagliotti et al, J Clin Oncol 2008
22 Différence 2000 s versus 2010 s Pemetrexed + Cisplatine (n=374) Gemcitabine + Cisplatine (n=107) OS: 11.6 ( ) PFS: 5.7 ( ) OS: 8.4 ( ) PFS: 5.7 ( ) Taxanes + Cisplatine (n=44) Vinorelbine + Cisplatine (n=91) OS: 9.6 ( ) PFS: 4.6 ( ) OS: 9.9 ( ) PFS: 5.3 ( ) NSqNSCLC only Schnabel et al, WCLC 2013
23 Pemetrexed: et les triple négatifs? Scagliotti et al, J Clin Oncol 2008
24 Stratégie triples négatifs #12 mois Pemetrexed platinum doublets (2010 s) Non squamous NSCLC Adapted from Pao W, Nat Rev Cancers 2010
25 CBNPC stades avancés Overall population 1 * Adenocarcinoma 2 OS estimate CP 0.8 Bevacizumab 15mg/kg + CP Months Median OS (months) CP: 10.3 Bevacizumab 15mg/kg + CP: 12.3 HR=0.79; p=0.003 OS estimate CP Bevacizumab 15mg/kg + CP Months Median OS (months) CP: 10.3 Bevacizumab 15mg/kg + CP: 14.2 HR=0.69 (95% CI: ) *69% of patients had adenocarcinoma Preplanned analysis 1. Sandler, et al. NEJM Sandler, et al. JTO 2010
26 Bevacizumab: OS benefit Soria JC et al, Ann Oncol 2013
27 Bevacizumab: risks 1. Sandler, et al. NEJM 2006; 2. Reck, et al. JCO 2009 Soria 3. Sandler, et al, et Ann al. ECCO Oncol
28 Clinical selection Bevacizumab eligible Clinical criteria Radiological criteria Haemoptysis Recent ATE Uncontrolled HT Cerebral mets Anticoagulation Age > 65y Crino et al, Lancet Oncol 2011; Besse et al, CCR 2009
29 Radiological selection Bevacizumab eligible Clinical criteria Radiological criteria Centrally located tumors* Cavitation? *24% for pts included in the SAiL trial; 39% for pts included in the AVAPERL trial Sandler et al, JCO 2009; Barlesi et al, Ann Oncol 2010; Reck et al, Ann Oncol 2011
30 Bevacizumab: Impact of continuation Received 6 cycles Completed 6 cycles Analysis population* Patients in ECOG 4599 n=869 CP + Bev n=429 CP n=440 CP + Bev n=258 (60%) CP n=194 (44%) Bev maintenance n=217 (51%) CP nonprogressors n=134 (30%) PFS estimate Bev/CP non-progressors CP non-progressors HR (adjusted)=0.64 p<0.001 OS estimate Bev/CP non-progressors CP non-progressors HR (adjusted)=0.75 p= Months (since treatment initiation) Months (since treatment initiation) Sandler et al., WCLC 2011
31 Stratégie triples négatifs #15 mois Bevacizumab platinum doublets (2010 s) Non squamous NSCLC Adapted from Pao W, Nat Rev Cancers 2010
32 Maintenance: Paramount (OS) Paz-Ares L et al, J Clin Oncol 2013
33 AVAPERL: design Induction CT 4 cycles, 21 days Maintenance CT Q3wks until PRG Primary endpoint Non-sp NSCLC stage IIIB IV Non pretreated PFS from randomization Bevacizumab + pemetrexed + cisplatine PRG Follow up CR/PR/SD By RECIST R Stratified by: Sex Smoking History Response at randomisation Arm A: bevacizumab Arm B: bevacizumab + pemetrexed Secondary endpoints Overall survival ORR + DCR Safety QoL Barlesi F et al, J Clin Oncol 2013
34 AVAPERL: PFS from randomisation 1.0 Median PFS PFS estimate m Bev+Pem: 7.4m Bev: 3.7m HR: 0.48; p< Months Barlesi F et al, J Clin Oncol 2013
35 AVAPERL: Updated Overall Survival Rittmeyer A et al, ASCO 2013
36 AVAPERL: Safety Randomised pts Bev + Pem (n=128) Bev (n=125) Grade 3/4 haematological AEs, % pts with event Grade 3/4 non-haematological AEs, % pts with event Haematological SAEs, % pts with event Non-haematological SAEs, % pts with event Barlesi F et al, J Clin Oncol 2013
37 Pointbreak trial 4 cycles Previously untreated, stage IIIB or IV, non-squamous NSCLC, treated CNS mets, PS 0 1 (n=939) R 1:1 Bevacizumab 15 mg/kg q3w + carboplatin + pemetrexed Bevacizumab 15 mg/kg q3w + carboplatin + paclitaxel Bevacizumab 15 mg/kg q3w + pemetrexed Bevacizumab 15 mg/kg q3w Treat to PD Treat to PD Primary endpoint OS Secondary endpoints ORR and DCR PFS and TTP safety and QoL Patel, IASLC Chicago 2012
38 Pointbreak trial 1.0 OS estimate Pem + CP + Bev Pac + CP + Bev HR=1.00 ( ) p= Time (months) Patel, IASLC Chicago 2012
39 Pointbreak trial Pem + CP + Bev Pac + CP + Bev OS estimate* Time (months) *, Exploratory, maintenance population only Patel, IASLC Chicago 2012
40 Pronounce trial (S130) Key patient inclusion criteria No prior systemic treatment ECOG PS 0-1 Stable IIIB-IV nonsquamous NSCLC Stable treated brain mets (n=361) R Induction phase 4 cycles, q3w Pem 500 mg/m 2 + Cb AUC6 (n=182) PD Stratification PS (0 vs. 1); sex (M vs. F); disease stage (M1a vs. M1b) Pac 200 mg/m 2 + Cb AUC6 + Bev 15 mg/kg (n=179*) Maintenance treatment q3w Pem 500 mg/m 2 (n=98) Bev 15 mg/kg (n=95) PD Primary endpoint PFS without Grade 4 AE (G4PFS) Secondary endpoints PFS, OS, RR, DCR Safety and tolerability Zinner et al. J Clin Oncol 31, 2013 (suppl; abstr LBA8003)
41 Pronounce trial (S130) Proportion Pem+Cb: median G4PFS = 3.9 mo Pac+Cb+Bev: median G4PFS = 2.9 mo Log-rank p value = HR (90% CI) = 0.85 ( ) Number of G4PFS events Pem+Cb (n=152) % Pac+Cb+Bev (n=144) % G4 AE PD Death Patients at Risk Zinner et al. J Clin Oncol 31, 2013 (suppl; abstr LBA8003)
42 Maintenance studies: OS Trial Drug Median OS Control Arm Continuation Maintenance Median OS Experim. Arm HR (95% CI) Brodowicz GMZ ( ) IFCT-GFPC GMZ ( ) Belani GMZ ( ) Paz-Ares PEM ( ) Barlesi PEM/BEV ( ) Switch Maintenance (Cx) Westeel VNR ( ) Fidias TXT ( ) Ciuleanu PEM ( ) Switch Maintenance (TKI) Saturn ERL ( ) Atlas ERL ( ) IFCT-GFPC ERL ( )
43 Stratégie triples négatifs #18 19 mois Pemetrexed Bevacizumab platinum doublets + maintenance (2010 s) Non squamous NSCLC Adapted from Pao W, Nat Rev Cancers 2010
44 2 nd line (INTEREST*) *Gefitinib vs Docetaxel Kim et al, Lancet 2008
45 2 nd line (TAILOR*) 1,0 HR = 0,68 (IC 95 : 0,50-0,93) ; p = 0,016 1,0 HR = 0,79 (IC 95 : 0,57-1,10) ; p = 0,167 0,8 0,8 0,6 0,6 0,4 0,4 0,2 Docétaxel 0,2 Docétaxel 0 Erlotinib Mois Erlotinib Mois Patients Événements Médiane (mois) SSP à 6 mois (%) Docétaxel ,0 31 Erlotinib ,2 16 *Erlotinib vs Docetaxel (EGFR WT only), KRAS WT subgroup Patients Événements Médiane (mois) SG à 6 mois (%) Docétaxel ,2 62 Erlotinib ,3 45 Garassino et al, ESMO 2013
46 2 nd line (DELTA*) Key patient inclusion criteria Advanced stage IIIB/IV NSCLC 1-2 previous chemotherapy regimens including at least 1 platinum agent ECOG PS 0-2 (n=300) R Erlotinib 150 mg/day (n=150) Stratification Gender; PS; histology; institution Docetaxel 60 mg/m 2 q3w (n=150) PD PD Primary endpoint PFS Secondary endpoints OS, RR and safety Analyses by wild type or mutant EGFR disease *Erlotinib vs Docetaxel (Japanese pop. only) Okano et al, ASCO 2013
47 2 nd line (DELTA*) Erlotinib Docetaxel HR (95% CI) p value PFS, months EGFR unselected EGFR wild type EGFR mutant 2.0 (n=150) 1.3 (n=109) 9.3 (n=21) 3.2 (n=151) 2.9 (n=90) 7.0 (n=30) ( ) ( ) ( ) OS, months EGFR unselected EGFR wild type EGFR mutant Not reached ( ) ( ) ( ) *Erlotinib vs Docetaxel (Japanese pop. only) Okano et al, ASCO 2013
48 AVAPERL: Subsequent lines * ** *, including 9 pts still under bev alone; **, including 19 pts stil under bev/pem Rittmeyer A et al, ASCO 2013
49 IFCT GFPC0502: Subsequent lines Bylicki O et al, J Thorac Oncol 2013
50 IFCT GFPC0502: Subsequent lines Bylicki O et al, J Thorac Oncol 2013
51 Agenda Définition & rationnel Standard actuel 1 ère ligne et maintenance 2 ème ligne et au delà Perspectives Priorités Soins de support
52 Améliorer utilisation sel de platine? Stratification PS, sex, prior (neo)adjuvant therapy Key patient inclusion criteria Stage IV or wet IIIB NSCLC ECOG PS 0-1 (n=275) R 2:1 RRM1 and ERCC1 determination by AQUA RRM1 low 40.5 RRM1 high RRM1 low 40.5 RRM1 high ERCC1 low 66.0 ERCC1 high Gemcitabine + carboplatin Gemcitabine + docetaxel Docetaxel + carboplatin Docetaxel + vinorelbine ERCC1 low 66.0 ERCC1 high Gemcitabine + carboplatin Bepler et al, ASCO 2013
53 Améliorer utilisation sel de platine? Gemcitabine + carboplatin Other treatment arms 1.0 Control Arm GCb Experimental Arm GCb 1.0 Control Arm (DCb, GD, or DV) Experimental Arm (DCb, GD, or DV) Progression-Free Survival (probability) Median PFS: (E) 5.0 mo (C) 8.1 mo log rank p=0.018 Progression-Free Survival (probability) log rank p= No. at risk Times (months) No. at risk Times (months) Bepler et al, ASCO 2013
54 Améliorer utilisation sel de platine? RRM1/ERCC1 Cx decision vs standard Cx Bepler G et al, J Clin Oncol 2013
55 Améliorer utilisation sel de platine? Key patient inclusion criteria Advanced NSCLC EGFR wt (n=382) R 1:1 Non-customised arm Cisplatin+docetaxel (n=190) Stratification ECOG PS 0/1; squamous vs. non-squamous; RAP80 tertiles; BRCA1 tertiles Gem/Cis for T1 RAP80 (T1-T3 BRCA1) (n=81) Doc/Cis for T2-T3 RAP80 (T1-T2 BRCA1) (n=62) Doc for T2-T3 RAP80 (T3 BRCA1) (n=49) Customised arm Primary endpoint PFS Secondary endpoints OS Tumour response rate Prematurely stopped at interim PFS analysis Moran et al, ASCO 2013
56 PARP inhibiteurs CR PR SD/PD/NE Max. change from baseline (%) GC Max. change from baseline (%) GCI Order of subjects Order of subjects Novello S et al, ESMO 2011
57 PARP inhibiteurs Probability of survival Time (Months) Median PFS, months (95% CI) GC (N=39) 4.3 (2.8, 5.6) GCI (N=80) 5.7 (4.6, 6.6) HR (95% CI) 0.89 (0.56, 1.41) p-value Novello S et al, ESMO 2011
58 Autres drivers oncogéniques? EGFR act mut 9.5% EGFR res mut 0.8% HER2 mut 0.9% UKN/Other 53.8% KRAS mut 27% N #10,000 ALK rearrangement 3.7% BRAF mut 1.7% PI3K mut 2.6% Barlesi F et al, ASCO 2013 #8000
59 BRAF mutations Paik PK et al, J Clin Oncol 2011
60 BRAF inhibition: TKI Vemurafenib Dabrafenib 15/03/ /08/2012 Gautchi et al, J Thorac Oncol 2011; Courtesy Julien Mazieres, Toulouse
61 BRAF inhibition: TKI Maximum Percent Reduction at Time of Best Disease Assessment *** *** *** Best Confirmed Response Partial response Stable disease Progressive disease * ** ** ** Smoking History * ** *** ** Nonsmoker Smoker, 40 pack years Smoker, > 40 pack years * ** * ** * ** ** * Planchard et al, ASCO 2013
62 BRAF inhibition: TKI On study treatment, n (%) 12 (48%) Median duration treatment (days) 0 3 months, n (%) > 3 6 months, n (%) > 6 12 months, n (%) > 12 months, n (%) 84 (9 480) 15 (60%) 4 (16%) 4 (16%) 2 (8%) Partial response Stable disease Progressive disease Not evaluable Not available First partial response Disease progressed Treatment Duration, months Planchard et al, ASCO 2013
63 HER2 mutations Liu et al, JTO 2010; Shigematsu et al, Cancer Res 2005; Cappuzzo et al, NEJM 2006
64 HER2 inhibition: anti HER2 Mazieres et al, J Clin Oncol 2013
65 HER2 inhibition: anti HER2 Mazieres et al, J Clin Oncol 2013
66 HER2 inhibition: anti HER2 Stage IV population on HER2 treatments Median PFS = 5.1 months Stage IV population Median OS = 22.9 months Mazieres et al, J Clin Oncol 2013
67 Bioguided strategies: emerging biomarkers KRAS (n=675) BRAF (n=29) PI3K (n=31) HER2 (n=13) Chemo 60, EGFR-TKI 0, Trial 2, Other 13, BSC 23, Barlesi F et al, ASCO 2013; Janne PA et al, Lancet Oncol 2013; Planchard D et al, ASCO 2013; Mazières et al, J Clin Oncol 2013
68 Traitements bioguidés: Acsé Programme ACSé (Crizotinib): Amplification d'alk Mutations d'alk Amplification de MET Mutations de MET Translocation de ROS1
69 Traitements bio-guidés: ROS evaluable patients : 2CRs and 20 PRs Overall response rate : 61% (95%CI: 44 77) Disease control rate : 81% (8 weeks), 67% (16 weeks) 50 Best change from beseline (%) ALK : treatment ongoing SD PR PD CR SHI Ou et al, WCLC 2013
70 HGF/c-met inhibiteurs: metmab Spigel D et al, J Clin Oncol 2013
71 HGF/c-met inhibiteurs: TKI Scagliotti G et al, WCLC 2013
72 Traitements bio-guidés: MEK Percent Change at Maximum Reduction from Baseline Measurement Sq C Sq C C C **** P P P P P P * Maximum tumor reduction from baseline is 0% C KRAS G12C KRAS codon 13 mutation Sq Squamous histology P Prior pemetrexed Five patients did not have a post baseline disease assessment. N RR DCR Median PFS, months (95% CI) All NSCLC 42 19% 69% 5.1 (2.8, 7.1) KRAS WT 19 21% 74% 4 PR, 10 SD 5.8 (2.8, 7.1) All KRAS % 65% 4.0 (1.3, 8.4) G12C 10 10% 60% 1 PR, 5 SD 4.0 (1.3, NR) Non G12C 13 23% 69% 3 PR, 6 SD 4.5 (1.4, 8.4) EGFR 5 20% 80% 1 PR, 3 SD ALK 1 1 PR Sq Sq Sq C C C Sq C C P P P P P P P P P P P P P P Pemetrexed cohort Mazieres et al, WCLC 2013
73 Traitements bio-guidés: MEK Percent Change at Maximum Reduction from Baseline Measurement * * * C KRAS G12C Squamous histology Best response was CR, single target lymph node <10mm Best response PD * * * N RR DCR Median PFS, months (95% CI) All NSCLC 47 32% 64% 3.5 (2.6, 6.3) KRAS WT 22 36% 68% 8 PR, 7 SD 4.2 (2.2, 7.6) All KRAS % 60% 3.4 (1.5, 6.3) G12C 10 40% 80% 4 PR, 4SD 4.8 (3.4, 13.3) Non G12C 15 20% 47% 1 CR, 2 PR, 4 SD 2.6 (1.2, 4.2) EGFR 4 50% 75% 2 PR, 1 SD ALK 2 2 SD C C C C C C C * C * * * 100 Seven patients did not have a post baseline disease assessment. Docetaxel cohort Bennouna et al, WCLC 2013
74 Essais bio-guidés globaux (triple négatif) Biopsy and molecular profiling EGFR mutation* Yes KRAS, KIT, No HRAS, No PTEN No ERBB2 No PDGFR-A No mutation NRAS, or AKT or PI3K mutation or BRAF, mutation or Amp* mutation* Amp* Yes Yes Yes Yes Other* Erlotinib AZD6244 MK2206 Lapatinib Sunitinib NOS N S T N S T N S T N S T N S T Disease progression Long-term follow-up Giaccone G et al, ASCO 2013
75 Essais bio-guidés globaux (triple négatif) NSCLC Enrolled Evaluable PR SD PD ORR% ERLOTINIB AZ LAPATINIB SUNITINIB MK Giaccone G et al, ASCO 2013
76 Essais bio-guidés globaux (double négatif) Stage IV NSCLC No EGFRm No ALK Fresh 2 cycles max CGH NGS SAPHIR02L-IFCT trial design (PI JC 4 cycles R Bioguided Rx (AZ pipeline: AZD2014, AZD4547, AZD5363, AZD8931, selumetinib, vandetanib) Standard Cx PMX (nsq) ERL (SQ) Until PRG No molecular alteration or Progression
77 Essais cliniques bio-guidés: survie Groupe Présence d un driver, pas de tt ciblé (A) N 313 Pas de Driver (B) 361 Présence d un driver, + tt ciblé adapté (C) 264 Médiane (années) 2,4 ans (1,8 à 2,9) 2,1 ans (1,8 à 2,5) 3,5 ans (3,2 à 4,6) Survie (%) 0.50 A C 0.25 B Temps (Années) 5 6 Kris MG et al, WCLC 2013
78 Essais cliniques bio-guidés (triple négatif) clinicaltrials.gov, access on December 11 th 2013
79 Stratégie triples négatifs #22 mois Non EGFR, non ALK, non KRAS bioguided trials Ex HER2 (2013 s) NSCLC Adapted from Pao W, Nat Rev Cancers 2010
80 Immunothérapie (anti-ctla4) Lynch et al, JCO 2012; Tomasini/Barlesi et al, Ther Adv Med Oncol 2011
81 Immunothérapie (anti-pd1) Topalian et al, NEJM 2012
82 Immunothérapie (anti-pd1/nivolumab) OS Mediane 9,9 mois (7,8; 12,4) OS 1 an 42% (48 pts at risk) OS 2 ans 24% (20 pts at risk) Survie (%) 0.50 OS 1 an 0.25 OS 2 ans Temps (Années) 54 Brahmer et al, WCLC 2013
83 Immunothérapie (anti-pdl1/mpdl3280a) Horn et al, WCLC 2013
84 Agenda Définition & rationnel Standard actuel 1 ère ligne et maintenance 2 ème ligne et au delà Perspectives Priorités Soins de support
85 Soins de support Tremel et al, N Engl J Med 2010
86 Denosumab? Scagliotti et al, J Thorac Oncol 2013
87 Stratégie triples négatifs? Triple negative lung cancer w optimized strategy (2013 s) NSCLC Adapted from Pao W, Nat Rev Cancers 2010
88 Conclusions NSq HER2 NSq BRAF NSq PI3K NSq Bev NSq Bev mtc NSq Non bev NSq Non bev mtc Sq mtc Sq non mtc NOS mtc NOS non mtc
89 Conclusions Entité spécifique? Personnalisation: tous triple négatifs? Optimisation des stratégies: Non bio-guidées Bio-guidées / nouveaux biomarqueurs Sélection (clinique et/ou biologique) Progrès en survie (triple negative BC?)
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