Stratégies thérapeutiques optimales en cas de positivité HER2, BRAF, ALK

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1 Stratégies thérapeutiques optimales en cas de positivité HER2, BRAF, ALK David Planchard (MD, PhD) Department of Cancer Medicine Thoracic Unit Gustave Roussy Villejuif (France)

2 Disclosure Slide AstraZeneca, BMS, GSK, Lilly, MSD, Pfizer, Roche, Sanofi, Pierre Fabre, Merck, Boehringer Ingelheim

drivers Stratification for EGFR, ALK and

3 Great advances have been made in lung cancer therapy: targeting of oncogenic drivers Stratification for EGFR, ALK and histology EFGR-activating mutation ALK translocation EGFR WT/ALKnon-squamous EGFR WT/ALKsquamous Erlotinib Gefitinib Afatinib Exon 20 T790M Osimertinib Crizotinib Ceritinib Alectinib 4 6 cycles Platinum-based doublet +/ bevacizumab +/- maintenance 4 6 cycles Platinum-based doublet ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; WT, wild-type

4 Frequency of genetic alterations 1-year nationwide programme in France analysed samples F.Barlesi et al, lancet 2016

5 Response rates to ALKi crizotinib in ALK+ NSCLC patients (phase I&II) ORR 61% ORR 60% D Ross Camidge et al, lancet onco 2012 Eunice L. Kwak et al, NEJM 2010

6 Efficacy of crizotinib according to the line of treatment >1 st line 1 st line Profile 1001 Profile 1005 Profile 1007 Profile 1014 N Phase I II III III ORR 61% 60% 65% 74% Median PFS

7 ESMO Clinical Practice Guidelines 2016

8 Most patients develop resistance to crizotinib usually within 1 2 years D. Ross Camidge et al, nature reviews 2014 ALK+ Crizotinib Progression Chimio / ALK-TKI

Understanding the molecular mechanisms underlying crizotinib resistance has led to the development of next-generation ALK inhibitors ALK TKI Status Ceritinib FDA approved (29 Apr 2014) EMA approved

9 Understanding the molecular mechanisms underlying crizotinib resistance has led to the development of next-generation ALK inhibitors ALK TKI Status Ceritinib FDA approved (29 Apr 2014) EMA approved (6 May 2015) Alectinib FDA approved (11 Nov 2015) Japan approved (4 Jul 2014) Brigatinib Ensartinib TSR-011 Entrectinib CEP Lorlatinib Investigational FDA Breakthrough Therapy Designation Investigational Investigational Investigational Investigational Investigational EMA, European Medicines Agency; FDA, Food and Drug Association. Doebele RC, et al. Clin Cancer Res. 2012;18: Katayama R, et al. Sci Transl Med. 2012;4:120ra17. Figure courtesy of A.T. Shaw; table compiled by J. Wolf.

Sum of longest diameter, maximum decrease from baseline (%) Best change from baseline (%)

100 80 60 40 20 0 20 40 60 80 100 120 80 40 0 40 80 Tumour change 1 Tumour change 3 * * * *

progressive disease; SD, stable disease.

10 Sum of longest diameter, maximum decrease from baseline (%) Best change from baseline (%) Next-generation ALK inhibitors have been shown to overcome crizotinib resistance effectively Tumour change 1 Tumour change 3 * * * * Prior crizotinib treatment No prior crizotinib treatment Disease progression or death Patients * * Patients ORR 62% DCR 93.5% Systemic BOR: PD (n = 22) SD (n = 35) PR (n = 61) NE (n = 1) Missing (n = 3) * * * * * * * * * *Chemotherapy-naïve patients. BOR, best overall response; DCR, disease control rate; ORR, overall response rate; PD, progressive disease; SD, stable disease. * * * * * * * Phase 1 ceritinib 2 PFS all 9m PFS crizo-naïve 18.4 m Phase 2 alectinib 3 ORR: 50% DCR: 79% PFS: 8.9 m 1. Shaw AT, et al. N Engl J Med. 2014;371: Felip E, et al. Presented at ESMO Abstract 1295P. 3. Ou SH, et al. J Clin Oncol. 2016;34:661-8.

11 Developing the optimal treatment sequence Next-generation ALK inhibitor vs chemotherapy post-crizotinib EML4 / ALK Crizotinib PD Ceritinib Alectinib Chemotherapy ASCEND-5 (NCT ) Phase 3, advanced NSCLC (n = 231): ceritinib vs docetaxel/pemetrexed (primary endpoint: PFS) ALUR (NCT ) Phase 3, advanced NSCLC (n = 120): alectinib vs docetaxel/pemetrexed (primary endpoint: PFS)

12 ASCEND -5: Kaplan-Meier Plots of PFS (BIRC) Probability of PFS (%) 100 Ceritinib 750 mg (N=115) Chemotherapy (N=116) Events, n (%) 83 (72.2) 89 (76.7) Median (95% CI), months 5.4 (4.1, 6.9) 1.6 (1.4, 2.8) HR (95% CI) 0.49 (0.36, 0.67) Log-rank p-value <0.001 Censoring times 0 No. of patients at risk Ceritinib Chemo Time (months) Giorgio Scagliotti et al, ESLO 2016

13 All-causality AEs in 20% of Patients Ceritinib (N=115) No. of patients (%) Chemotherapy (N=113) Preferred term All grades Grades 3/4* All grades Grades 3/4* Diarrhoea 83 (72.2) 5 (4.3) 20 (17.7) 1 (0.9) Nausea 76 (66.1) 9 (7.8) 26 (23.0) 2 (1.8) Vomiting 60 (52.2) 9 (7.8) 6 (5.3) 1 (0.9) ALT increased 49 (42.6) 24 (20.9) 10 (8.8) 2 (1.8) Decreased appetite 48 (41.7) 2 (1.7) 22 (19.5) 3 (2.7) AST increased 42 (36.5) 16 (13.9) 5 (4.4) 1 (0.9) Weight decreased 34 (29.6) 3 (2.6) 7 (6.2) 1 (0.9) Fatigue 31 (27.0) 6 (5.2) 32 (28.3) 5 (4.4) Asthenia 26 (22.6) 6 (5.2) 21 (18.6) 7 (6.2) ALP increased 26 (22.6) 7 (6.1) 1 (0.9) 0 (0.0) GGT increased 26 (22.6) 24 (20.9) 2 (1.8) 1 (0.9) Abdominal pain 25 (21.7) 1 (0.9) 11 (9.7) 1 (0.9) Back pain 25 (21.7) 1 (0.9) 8 (7.1) 3 (2.7) Alopecia 6 (5.2) 0 (0.0) 24 (21.2) 0 (0.0) Neutropenia 4 (3.5) 1 (0.9) 23 (20.4) 17 (15.0) ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl-transferase *Grade 3/4 AEs were reported in 89 (77.4%) patients receiving ceritinib and 72 (63.7%) patients receiving chemotherapy Giorgio Scagliotti et al, ESLO 2016

14 Developing the optimal treatment sequence Next-generation ALK inhibitor as 1st-line treatment EML4 / ALK PFS1: 11 m Crizotinib PD PFS2: 7 9 m Ceritinib Alectinib PFS1 + PFS2? Next generation ALK inhibitor Ceritinib Alectinib

15 Change from baseline in sum of tumour diameters (%) Phase II Study of Ceritinib in ALKi-naïve Patients with ALK+ NSCLC: Single-arm, Open-label A decrease in tumour burden from baseline was shown in 108/114 (94.7%) patients Ceritinib 750 mg/day (n=114) *** 100 Patients had measurable baseline disease and at least one post-baseline (investigator) assessment *Three patients are not shown since in these patients disease progression was based on only non-target or new lesions Responder (complete response/partial response) Stable disease Progressive disease Unknown Enriqueta Felip et al, ESLO 2016

16 Results: PFS Probability of PFS (%) Investigator BIRC Events, n (%) 70 (56.5) 65 (52.4) Median (95% CI), months 16.6 (11.0, 22.1) 18.4 (10.9, 26.3) Censoring time Time (months) Enriqueta Felip et al, ESLO 2016 No. of patients at risk Investigator BIRC

17 % Change from Baseline % Change from Baseline J-ALEX Phase III Crizotinib vs Alectinib: Objective Tumor Response ORR assessed by investigator in ITT population ORR [95%CI] Alectinib (N=103) ORR* assessed by IRF Alectinib (n=83) Crizotinib (N=104) 85.4% [ ] 70.2% [ ] CR or PR Crizotinib (n=90) Water fall plot* assessed by IRF Alectinib (n=83) CR or PR SD, PD or NE ORR [95%CI] 91.6% [ ] 78.9% [ ] CR or PR Crizotinib (n=90) Presented by: Hiroshi Nokihara

18 Progression-free survival rate (%) Primary Endpoint: PFS by IRF (ITT Population) Alectinib Crizotinib (N=103) (N=104) Events, n (%) 25 (24.3%) 58 (55.8%) 100 Median, mo [95% CI] NR [ NR] 10.2 [ ] P-value < HR [ % CI] 0.34 [ ] 60 NR No. of patients at risk Alectinib Crizotinib months Time (months) Presented by: Hiroshi Nokihara

19 ALEX (NCT ) Global phase 3 study, advanced NSCLC (n = 303): alectinib vs crizotinib primary endpoint: PFS ASCEND-4 (NCT ) Phase 3, advanced NSCLC (n = 376): ceritinib vs cisplatin/pemetrexed or carboplatin/pemetrexed primary endpoint: PFS 23 Sep 2016 press release: primary endpoint met EML4 / ALK

Best change from baseline (%) Developing the optimal treatment sequence EML4 / ALK PFS1: 11 m Crizotinib PD PFS2: 7-9 m Ceritinib Alectinib Lolartinib 1 Ongoing treatment Brigatinib 2 40 20 0 20 40

20 Best change from baseline (%) Developing the optimal treatment sequence EML4 / ALK PFS1: 11 m Crizotinib PD PFS2: 7-9 m Ceritinib Alectinib Lolartinib 1 Ongoing treatment Brigatinib How to treat relapse after second-generation ALK inhibitors 1 prior TKI 2 prior TKI = 1 TKI 2 TKIs ORR, % mg q.d. * = 1 TKI 2 TKIs ORR, % 59 *? PFS, months PFS, months Solomon BJ, et al. ASCO J Clin Oncol. 2016;34 Suppl:abstract Kim D-W, et al. ASCO 2016; J Clin Oncol. 2016;34 Suppl:abstract 9007.

21 Brigatinib, Lorlatinib.3nd generation Lorlatinib Zou HY, et al. AACR-NCI 2013, poster A277

22 Best change from baseline (%) Lorlatinib Showed Promising Clinical Activity CNS Responses in ALK/ROS1+ Patients with Measurable Disease R R Ongoing treatment No prior TKI 1 prior TKI 2 prior TKI Indicates the patients with ROS1 rearrangements R R R ALK, anaplastic lymphoma kinase; PD, progressive disease; ROS1, c-ros oncogene 1; TKI, tyrosine kinase inhibitor 22

23 ESMO Clinical Practice Guidelines

24 Out of EGFR and ALK there are many other potential driver mutations in lung adenocarcinoma analysed samples F.Barlesi et al, lancet 2016

Vemurafenib in NSCLC with BRAF V600 mutations Target tumour diameter sum (% change from baseline) Basket trial (multiple non-melanoma cancers) Variable Patients with 1 postbaseline assessment, n

(27) Missing data, n (%) 1 (5) 0 0 OR, n (%) [95% CI] 8 (42) [20 67] 0 1 (4) [< 1 20] 100 80 60 40 20 0 20 40 60 80 100 NSCLC cohort mpfs: 7.3 months (95% CI 3.5 10.

25 Vemurafenib in NSCLC with BRAF V600 mutations Target tumour diameter sum (% change from baseline) Basket trial (multiple non-melanoma cancers) Variable Patients with 1 postbaseline assessment, n NSCLC a (N = 20) Colorectal cancer a Vemurafenib (N = 10) Vemurafenib + cetuximab (N = 27) CR, n (%) PR, n (%) 8 (42) 0 1 (4) SD, n (%) 8 (42) 5 (50) 18 (69) PD, n (%) 2 (11) 5 (50) 7 (27) Missing data, n (%) 1 (5) 0 0 OR, n (%) [95% CI] 8 (42) [20 67] 0 1 (4) [< 1 20] NSCLC cohort mpfs: 7.3 months (95% CI ) a Patients with several pre-specified cancers were enrolled into the study, including NSCLC and colorectal cancer. CI, confidence interval; CR, complete response; mpfs, median PFS; OR, overall response; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease. Hyman DM, et al. N Engl J Med. 2015;373:

26 BRF study design Multicohort, non-randomized, open-label phase 2 study Cohort A (dabrafenib monotherapy) planned n = 60 Interim futility analysis Stage IV NSCLC BRAF V600E ECOG PS platinum-based chemotherapy Dabrafenib 150 mg b.i.d. Stage 1 n = 20 Stage 2 n = 20 Expansion n = 20 n = 78 ( 2nd line) Cohort B (combination dabrafenib + trametinib) planned n = 40 Stage IV NSCLC BRAF V600E ECOG PS prior treatments 1 platinum-based chemotherapy Dabrafenib 150 mg b.i.d. Trametinib 2 mg q.d. Stage 1 n = 20 Stage 2 n = 20 n = 57 (2nd 4th line) Cohort C (combination dabrafenib + trametinib in 1st line) planned n = 25 Stage IV NSCLC BRAF V600E ECOG PS 0 2 No prior treatment Dabrafenib 150 mg b.i.d. Trametinib 2 mg q.d. n = 34 ENROLLMENT COMPLETED b.i.d., twice daily; ECOG, Eastern Cooperative Oncology Group; PS, performance status; q.d., once daily. Planchard D, et al. Lancet Oncol. 2016;17: Planchard D, et al. Lancet Oncol. 2016;17:

27 Maximum percent reduction from baseline measurement Dabrafenib monotherapy: maximum reduction Best response 2nd line (N = 78) Response rate (confirmed CR + PR) 32% 95% CI ( ) DCR (CR + PR + SD) 56% 95% CI ( ) Best confirmed Confirmed response Response PR SD PD NE DCR, disease control rate; NE, not evaluable. Planchard D, et al. Lancet Oncol. 2016;17:

28 PFS Dabrafenib monotherapy: Progression-free survival (independent review) No. at risk Time from first dose (months) Independent PFS: 5.5 months (95% CI ) Planchard D, et al. Lancet Oncol. 2016;17:

Case study Dabrafenib Activity in BRAF V600E NSCLC 72 year old

in1985) ECOG PS2 Adenocarcinoma, BRAFV600E, T3N3M1b (pleural,

platinum-pemetrexed October 2012 + 6 weeks of Dabrafenib Baseline

29 Case study Dabrafenib Activity in BRAF V600E NSCLC 72 year old white female, 2 nd line, former smoker, 10 pack years (stop in1985) ECOG PS2 Adenocarcinoma, BRAFV600E, T3N3M1b (pleural, pulmonary, lymph nodes) Progression after one line of platinum-pemetrexed October weeks of Dabrafenib Baseline CT-Scan J. Mazieres et al, Hôpital Larrey CHU Toulouse ECOG PS0 D.Planchard et al, ESMO 2014

30 J. Mazieres et al, Hôpital Larrey CHU Toulouse D.Planchard et al, ESMO 2014 ECOG PS:0 Asymptomatic Very good safety profile (rare episodes of fever) September 2014 Unique residual disease in the lower left lung Discussion for a local treatment 2 years after the start of dabrafenib

31 Double inhibition BRAF et MEK Kristina M. Ilieva et al, mol cancer therapeutics

32 Dabrafenib + trametinib: best confirmed response Investigator assessment (n = 57) Independent assessment (n = 57) ORR (CR + PR), n (%) [95% CI] 36 (63) [49 76] 36 (63) [49 76] Best response, n (%) CR PR SD a PD Non-CR/non-PD b NE 2 (4) 34 (60) 9 (16) 7 (12) 0 5 (9) 0 36 (63) 4 (7) 8 (14) 3 (5) 6 (11) DCR (CR + PR + SD), n (%) [95% CI] 45 (79) [66 89] 43 (75) [62 86] a SD is defined as meeting SD criteria for 12 weeks. b Patients were non-measurable by independent review committee. Planchard D, et al. Lancet Oncol. 2016;17:

33 Dabrafenib + trametinib: maximum change in target lesion Maximum reduction from baseline measurement (%) Maximum change in target lesion by best investigator-assessed confirmed response ORR: 63% (95% CI 49 76) Best confirmed response CR PR SD PD NE Patients NE patients either had no post-baseline CT scan or discontinued before 12 weeks without documented progression. Planchard D, et al. Lancet Oncol. 2016;17:

34 Progression-free survival with dabrafenib and trametinib in 2nd line Progression-free survival by investigator assessment Cohort B PFS, median (95% CI), mo Number of progressions or deaths, n (%) Time from first dose (months) Investigator 9.7 ( ) 32 (56) Independent 8.6 ( ) 34 (60) No. at risk No. censored Dashed lines represent 95% CI Median follow-up of 11.6 months; mo, month Planchard D et al. Lancet Oncol 2016;17:

with pleural effusion, liver metastases, 4th

Baseline (July 2014) Dabrafenib + trametinib +25

reduction (confirmed and still response, 73% +25

35 Dabrafenib + trametinib: case study 1 61-year-old woman, never smoked Adenocarcinoma with pleural effusion, liver metastases, 4th line (CDDP-pemetrexed, docetaxel, gemcitabine) Baseline (July 2014) Dabrafenib + trametinib +25 months (August 2016) PR at Week 6 with 54% reduction (confirmed and still response, 73% +25 months) CDDP, cisplatin. Planchard D, et al. Gustave Roussy Villejuif.

36 Selected adverse events for dabrafenib vs combination therapy of dabrafenib and trametinib in 2nd line treatment of BRAF+ NSCLC Category AEs, n (%) All grades Grade 3 All grades Grade 3 General Skin Digestive Dabrafenib + trametinib Dabrafenib Pyrexia 26 (46) 1 (2) 30 (36) 2 (2) Asthenia 18 (32) 2 (4) 25 (30) 3 (4) Decreased appetite 17 (30) 0 24 (28) 1 (1) Chills 13 (23) 1 (2) 13 (15) 1 (1) Peripheral edema 13 (23) 0 Arthralgia 11 (19) 0 14 (17) 1 (1) Dry skin 15 (26) 1 (2) 19 (23) 0 Rash 12 (21) 1 (2) 17 (20) 1 (1) Hyperkeratosis 6 (10) 1 (2) 25 (30) 1 (1) Basal-cell carcinoma 2 (2) 1 (2) 4 (5) 4 (5) Squamous-cell carcinoma 2 (4) 2 (4) 10 (12) 10 (12) Skin papilloma 22 (26) 0 Nausea 23 (40) 0 23 (27) 1 (1) Vomiting 20 (35) 0 17 (20) 1 (1) Diarrhea 19 (33) 1 (2) 14 (17) 1 (1) Planchard D et al. Lancet Oncol 2016;17:

37 Hyman DM, et al. N Engl J Med. 2015;373: Gautschi O, et al. J Thorac Oncol. 2015;10: Planchard D, et al. Lancet Oncol. 2016;17: Planchard D, et al. Lancet Oncol. 2016;17:

38 Out of EGFR and ALK there are many other potential driver mutations in lung adenocarcinoma analysed samples F.Barlesi et al, lancet 2016

39 Yamamoto H, JNCI 2014 HER2: physiopathologie Principales mutations/insertions de HER2 Insertion de l exon 20 de 3 à 12 pdb. Entre les codons 775 and 881 : 12 pdb : 83% entrainant une insertion de 4 AA(YVMA). Insertion de 3 pdb 8% Mutations ponctuelles exon 20 : L755S et G776C 8%. Mutations de l exon 17 : G660D, V659E.

40 HER2: addiction oncogénique Perera SA, PNAS 2008 Observation d adénocarcinomes distaux (ou adénosquameux) : anapath et IRM.

41 Mutation HER2 HER2 specific treatments: trastuzumab, Lapatinib, Afatinib,, masatinib Patient 1 st line T Patients de stade IV traités avec des anti-her2 Best disease response 1 VIN-HER PR 2 CAR-PAC-TRAS SD 3 TXT-MASA PD 4 VIN-TRAS PR 5 CAR-PAC-TRAS PR 6 VIN-TRAS PR 7 VIN-TRAS SD 8 LAP PD 9 NVB-HER PR 2 nd line T Best disease response 3rd line T Best disease response 4th line T Best disease response 10 LAP PD TRAS-VIN PR AFA SD CAR-TRAS SD 11 VIN-TRAS PD 12 DOC-TRAS PR 13 VIN-TRAS PR AFA PR 14 VIN-TRAS PR AFA SD 15 VIN-TRAS SD PAC-TRAS SD 16 TRAS PR SD: Stable Disease, PR: Partial Response, PD: Progressive disease, NE: non evaluated Conventional treatment: CAR: Carboplatin, PAC: Paclitaxel, VIN: Vinorelbin, DOC: Docetaxel. HER2 specific treatments: TRAS: Trastuzumab, LAP: Lapatinib, AFA: Afatinib, MASA: masatinib Taux de controle de la maladie: 96% pour le trastuzumab (n = 15), 100 % pour afatinib (n = 4) Julien Mazieres et al., JCO 2013

42 Torisel +Neratinib N=60; 49 evaluable HER2-mutated NSCLC n=6 Gandhi et al, J Clin Oncol 2014; 32(2): 68-75

43 Phase I trial of neratinib (pan-her) + torisel (mtor) showed evidence of activity against HER2 mutant NSCLC Gandhi et al, ASCO 2011

44 Change from baseline (%) Change in sum LD (%) Targeting HER2 aberrations HER2 mutations in 1 4% and HER2 amplifications in 2 5% of lung ADC 60 Dacomitinib (pan-her inhibitor) (HER2-mutated or amplified NSCLC) 100 PD Neratinib (pan-her inhibitor) ± temsirolimus (mtor inhibitor) (HER2-mutated NSCLC) Partial response n = PD PD Partial response 0 (0) 3 (21)* PD SD SD SD SD SD PD SD * * SD SD SD SD SD SD PD SD SD SD SD * SD SD PR PR PR 30% threshold for reduction in tumour burden (response) HER2 mutation HER2 amplification Only 3/26 of HER2-mutant patients had a response (ORR 12%) 100 Neratinib Neratinib + temsirolimus 21% ORR and mpfs of 4 months * Patients had < 20% increase in tumour burden, but were considered PD due to the appearance of new lesions Kris MG, et al. Ann Oncol. 2015; 26: Besse B, et al. Presented at ESMO Abstract LBA 39.

Hyman DM, et al. N Engl J Med. 2015;373:726-36. Gautschi O, et al. J Thorac Oncol. 2015;10:1451-7.

45 Hyman DM, et al. N Engl J Med. 2015;373: Gautschi O, et al. J Thorac Oncol. 2015;10: Planchard D, et al. Lancet Oncol. 2016;17: Planchard D, et al. Lancet Oncol. 2016;17:

46 In summary. Diagnostic workup Molecular profiling 1. Multidisciplinary discussion to determine optimal procedure for tissue procedure 2. Biopsy 3. Morphology 4. Review of patient and tumour data Integrated NGS-based assay to detect mutations, amplifications, and translocations Patient selection Treatment EGFR ALK BRAF ROS1 RET MET exon 14mut/Amp NTRK1/2/3 HER2 No actionable alterations 1. Firstgeneration EGFR TKI 2. Thirdgeneration EGFR TKI 1. Crizotinib 2. 2nd or 3nd ALK TKI (Ceritinib, alectinib, Brigatinib) Dabrafenib + trametinib Vemurafenib Crizotinib Ceritinib Lorlatinib Cabozantinib Cabozantinib Vandetanib Sunitinib Crizotinib Cabozantinib Glesatinib Entrectinib Trastuzumab Neratinib+/- Temsirolimus Afatinib Dacomatinib Chemotherapy or immunotherapy Treatment cessation Subsequent therapies Treatment until response, progressive disease, or unacceptable adverse effects Therapy switch/combination based on re-biopsies or liquid therapy Adapted from Thomas A, et al. Nat Rev Clin Oncol. 2015;12:

47 ALK+ TKI + Immunotherapy.? EGFR+

48 Thoracic Molecular Tumor Board ON- PURPOSE FRESH TUMOR BIOSPSY & PATHOLOGY CONTROL MOLECULAR PROFILING (CGH & NGS) MOLECULAR TUMOR BOARD Since 2010 TREATMENT

49 Acknowledgments Jean-Charles SORIA Benjamin BESSE Thierry LE CHEVALIER MERCI!

Molecular Targets in Lung Cancer

Molecular Targets in Lung Cancer Robert Ramirez, DO, FACP Thoracic and Neuroendocrine Oncology November 18 th, 2016 Disclosures Consulting and speaker fees for Ipsen Pharmaceuticals, AstraZeneca and Merck