Breast Cancer in New Treatments

Transcription

1 Breast Cancer in 2016 New Treatments Pr. Lionel D Hondt (M.D., Ph.D.) Head of the Department of Oncology CHU UCL Namur Belgian Pharmacy Oncology Practitioners (BPOP) Blankenberg February 12th 2016

2 Plan Epidemiology and prognosis Treatments for metastatic diseases hormonotherapy chemotherapy targeted therapies CDK4 6 inhibitors anti PARP supportive cares Adjuvant and neoadjuvant treatments Research and conclusions

3 Epidemiology and Prognosis 1 st cancer in woman (35%), 1/8 (1/7 in 20 years?) ¾cases > 50 years old (menopause) incidence Incidence in Belgium (2008) 178/ /year 1 st cause of cancer death in woman (20%) 1 st cause of death in women years mortality 1,3%/year Survie à5 ans = 88%

4 Epidemiology and Prognosis 5 to 10 % metastatic at presentation 20 to 30% of localised diseases will evolve to metastatic cancer 5 year survival = 15 to 20% Medium survival 30 to 36 months (huge heterogeneity) More frequently luminal B, triple negatives, Her2+ (+ rare) Familial BC: BRCA 1 2 mutations, 70 years: 60 to 85%

5 Prognosis Factors related to patients Age Performance status / Comorbidities Factors related to the disease Free interval without metastasis (5 ans) Metastatic sites (bone, node and skin vs visceral) Number of metastases Prior adjuvant treatment

6 Pronostic Factors related to the tumor Degree of hormonal receptor positivity HER2 status Hormonal receptors ER+/ PR + about 70% Over representation if non visceral métastases HER2 status anti HER 2 therapies Anthracyclines Predictive factor of relative hormone resistance 6

7 Prognosis ER / PR / HER 2 status modifications up to 30% modifications during tumoral evolution Re biopsy and reanalyse these factors at relapse and/or progression (as frequent as possible) 7

8 Prognosis Multiple studies No difference if adjusted to biological characteristics Tung et al, Brest Cancer Res Treat

9 Prognosis 9 Schroeder et al Rev Med Liège 2015, 70 (3): 140-7

10 TREATMENTS FOR METASTATIC DISEASE 10

11 Hormonotherapy ESMO guidelines Hormonal therapy is the preferential option for HR+ metastatic breast cancer either visceral excepted if hormonal resistance is suspected or proven or if rapid tumoral debulking is needed. Visceral crisis? Choice of the hormone therapy drug is based on the previous treatment administered. Reimbursement criteria TAM AI (S/NS) AI (S/NS) Fulvestran

12 Hormone resistance

13 Hormone resistance 13

14 Chemotherapy Monotherapy Polychemotherapy in case of rapid progression Anthracyclines taxanes vinorelbine capecitabine gemcitabine platin based chemo (TNBC) eribuline.

15 EMBRACE STUDY 13,1 vs 10, 6 months 15 Cortès et al Lancet 2011, 377:

16 Chemotherapy Reimbursement criteria Etirinotecan topo 1 inhibitor BEACON study randomized phase II refractory BC anthracyclines, taxanes, (capecitabine)vs investigator choice(most eribuline) 2 months OS (NS because 3 months expected) favorable role if cerebral metastasis 16

17 Targeted Therapies: Pertuzumab 17

18 Targeted Therapies: Cleopatra 18

19 Targeted therapies: Cleopatra Baselga J et al. NEJM 2012, 366:

20 Targeted therapies: Cleopatra 20

21 Targeted therapies Phase IIIb Peruse study (Hubber et al) 28% patients (received Trastuzumab in adjuvant setting) >< Cleopatra (11%) Paclitaxel ou nab Paclitaxel + pertuzumab First results encouraging (ECCO 2015) in term of tolerability Efficacy? 21

22 Targeted therapies 22

23 Targeted therapies: Emilia 23

24 Targeted therapies: Emilia 24 Verma S et al. NEJM 2012, 367:

25 Targeted therapies: Emilia 25 Verma S et al. NEJM 2012, 367:

26 Targeted therapies: Marianne 26

27 Targeted therapies: Marianne ASCO 2015 (Ellis P et al.) Median follow up: 35 months PFS non inferior (not superior) OS not reached yet ORR similar Duration of response if TDM 1 TDM 1 better tolerated TDM 1 later of QoL 27

28 Bevacizumab in metastatic BC AVADO study Phase II E2100 study Milles D et al JCO 2010 Miller K et al NEJM

29 Bevacizumab in metastatic BC Ribbon-1 Robert N et al JCO

30 CDK4 6 inhibitors 30

31 CDK4 6 inhibitors 31

32 Palbociclib Paloma 3 32 Turner NC et al NEJM :

33 Palbociclib Paloma 3 33

34 Palbociclib Paloma 3 34

35 Neo/adjuvant treatments 35

36 Amsterdam signature 36 Van t Veer et al Nature 31, 415: 2002

37 Microarrays Carey L: JAMA 2006, 21:

38 Microarrays Prevalence was: luminal A = 51%, luminal B = 16%, basal-like = 20%, HER2+/ER = 7%, and unclassified = 6%. 38 Carey L: JAMA 2006, 21: 2

39 Mindact Study C Bernard-Marty: Bull Cancer 2006; 93:

40 Prospective validation of a 21 gene expression assay in breast cancer 40 Sparano J et al NEJM Nov 19; 2015

41 Duration of Hormone therapy 41 ATLAS study Davies C et al Lancet Mar patients ER +, ER, ER unknown 5 vs 10 years ER + All endpoints + (mainly second decade after diagnosis: ½BC mortality) More side effect: pulmonary embolus stroke ischemic cardiopathy endometrial carcinoma

42 Duration of Hormone therapy Recurrence BC mortality 42 Davies C et al Lancet Mar 2013

43 Ovarian Suppression and Chemotherapy PROMISE GIM6: Lambertini M et al JAMA dec pre MP women receiving CT (stage I to III) Triptorelin (Decapeptyl ) /4 weeks Menstrual resumption 72,6 vs 64,0% (HR 1,48 p < 0,006 if age adjusted) No pregnancies (2,1 vs 1,6%) No statistical 5years DFS (80,5 vs 83,7%) (HR ) Meta analysis + but conflicting results in studies Not yet recommended 43

44 Ovarian Suppression and Chemotherapy Lambertini M et al JAMA dec

45 Ovarian Suppression and Chemotherapy 45 Lambertini M et al JAMA dec 2015

46 Dose dense adjuvant CT GIM 2 study Del Mastro L et al. Lancet May 2015 Phase III (2 x 2) trial Role 5 FU and dose dense (2 versus 3 weeks) 2091 patients EC Paclitaxel vs FEC Paclitaxel Pegfilgrastim 46

47 Dose dense adjuvant CT 47 Del Mastro L et al Lancet May 2015

48 Dose dense adjuvant CT HR+ HR - 48 Del Mastro L et al Lancet May 2015

49 EFS Predictive value of pcr after neoadjuvant CT (EORTC 10994/BIG 1 00) EFS Bonnefoi H et al Ann Oncol June

50 Predictive value of pcr after neoadjuvant CT (EORTC 10994/BIG 1 00) EFS 50 Bonnefoi H et al Ann Oncol June 2014

51 Neoadjuvant platin CT and BRCA1 mutation women from 3 centers in Poland Mutations BRCA1 CDDP 75 mg/m2 x 4 cycles Mastectomy 4 FEC 61% pcr Phase II uniarm Birsky Breast Cancer Res Treat

52 Research and Conclusions TNBC with AR Enzalutamide until progression Phase II 118 pts 50% 1 st ou 2 d line At 16 weeks: 35 % clinical benefit (75 pts evaluables) 2 CR, 7 PR MedianPFS 14,4 weeks Benefit superior if genetic signature linked to AR (47% pts). OS: 32,1 weeks vs not reached

53 Research and Conclusions Personnalised medecine Safir 01 study (UNICANCER Fabrice André) 423 pts metastatic breast cancer 2/3 cas whole genome sequencing 46% (195 pts) mutation corresponding to a targetable 13% received targeted therapies (28% pts with identified abnormalities) Feasable Résults?

54 Research and Conclusions Major advances New treatements New concepts New strategies Improvements in PFS, OS Better QoL Identification of patients at risk (BRCA1, ) Important costs 54

55 Costs Price of Kadcyla: 1.652,42 /vial 100 mg and 2.639,61 /vial 160 mg = /cycle (70 kg) Price of Perjeta: /vial 420 mg (loading dose = 840 mg) How can we afford that? How to better select patients? 55

56 Other treatments: physical activity Primary prevention: 9 MET/h 4 h walking/week 2h bicycling, sport/week Secondary prevention mortality by 41% cancer mortality by 34% relapse by 24% tolerability osteoporosis, arthralgia, sarcopenic obesity 56

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59 Merci de votre attention

60 Merci de votre attention