Current and Future perspectives of HER2+ BC

Transcription

1 GBCC Satellite symposium Current and Future perspectives of HER2+ BC Jee Hyun Kim, M.D., Ph.D. Seoul National University Bundang Hospital Seoul National University College of Medicine

2 Disclaimer All the contents in the presentation is owned by the speaker and does not necessarily represent the views and opinions of Roche Korea. It may contain therapies currently under clinical development for the purpose of scientific discussion and the company does not recommend any off-label uses. Physicians should refer to the approved PI before prescription.

3 Current status OVERVIEW OF ANTI-HER2 TREATMENT IN EBC

4 ` Slamon DJ et al, science 1987;235:

5 Trastuzumab: An anti-her2 antibody A humanised IgG1, anti-her2 monoclonal antibody that binds with high affinity and specificity to subdomain IV, a juxta-membrane region of the HER2 extracellular domain 1 Trastuzumab inhibits HER2 intracellular signalling, thereby inhibiting the proliferation of human tumour cells that overexpress HER2 1 Trastuzumab is a potent mediator of ADCC 1 Abrogation of HER2-mediated intracellular signalling by trastuzumab 3 HER2 Trastuzumab HERCEPTIN 1. EMA. Herceptin SmPC. October 2016; 2. FDA. Herceptin PI. March 2016; 3.

6 Survival probability Survival probability Taxane + trastuzumab significantly improved OS vs taxane alone in HER2-positive mbc H0648g 1 M H + CT (n = 235) CT (n = 234) 1.0 H + T (n = 92) T (n = 94) RR (95% CI) = 0.80 ( ) p = p = Time (months) Time (months) 1. Slamon DJ, et al. NEJM 2001;344: ; 2. Marty M, et al. J Clin Oncol 2005;23: ; 3. Jackisch C. Oncologist 2006;11 Suppl 1:34 41.

7 Four adjuvant trastuzumab trials in HER2 positive EBC Extensive clinical programme involving > patients Study N Treatment arms HERA BCIRG CT* ± RT observation CT* ± RT trastuzumab 1 year CT* ± RT trastuzumab 2 years AC docetaxel AC docetaxel + trastuzumab trastuzumab Docetaxel + carboplatin + trastuzumab trastuzumab Median FU (years) Cross-over 11 52% % NCCTG N NSABP B Arm A: AC paclitaxel Arm B: AC paclitaxel trastuzumab 8.4 Arm C: AC paclitaxel + trastuzumab trastuzumab AC paclitaxel AC paclitaxel + trastuzumab trastuzumab % 1. Goldhirsch Lancet Oncol 2013;82: Slamon Cancer Res 2016;763. Perez J Clin Oncol 2014;32:

8 DFS event-free (%) Joint analysis: DFS at 8.4 years after randomization 40% reduction in risk of DFS event with trastuzumab after 8.4 years AC PH AC P 81.4% 76.8% 73.7% 11.5% 69.5% 64.9% 62.2% No. at risk N Events AC PH AC P HR: 0.60 (95% CI: ); p < Years from randomisation HR, hazard ratio Romond EH, et al. SABCS 2012 (Abstract S5-5) Perez EA, et al. J Clin Oncol 2014; 32:

9 Survival (%) Joint analysis: OS at 8.4 years after randomization Addition of trastuzumab was associated with a 37% relative risk reduction after 8.4 years follow-up AC P 93.2% 90.3% 89.8% 84.3% 87.0% 79.4% AC PH = 2.9% = 5.5% = 7.6% = 8.8% 84.0% 75.2% 8.8% Years from randomisation No. at risk N Events AC PH AC P HR: 0.63 (95% CI = 0.54, 0.73); p < Romond EH, et al. SABCS 2012 (Abstract S5-5); Perez EA, et al. J Clin Oncol 2014; 32:

10 Survival (%) Joint analysis: Magnitude of OS benefit consistent irrespective of HR status HR-positive HR-negative AC P AC PH 86% 77.1% AC PH AC P 81.6% 73% No. at risk N Events AC PH AC P HR: 0.61 (95% CI = ); p < HR: 0.64 (95% CI = ); p < Years from randomisation Romond EH, et al. SABCS 2012 (Abstract S5-5); Perez EA, et al. J Clin Oncol 2014; 32: N Events AC PH AC P

11 Alive and disease-free (%) NCCTG N9831: DFS for sequential vs. concurrent trastuzumab Non-significant* DFS benefit for concurrent treatment % 80.1% AC PH AC P H No. at risk n Events HR 95% CI p value* Years from randomisation * Significant p value predefined as p = Perez EA, et al. J Clin Oncol 2011; 29:

12 Trastuzumab significantly improved OS in patients with HER2-positive EBC after long-term follow-up HERA: H vs. observation 1 11 years median follow-up a BCIRG 006: H in combination with different chemotherapy regimens 2, years median follow-up Time (years) Trastuzumab IV approval in HER2-positive ebc The HERA, BCIRG 006 and NCCTG N9831/NSABP B-31 studies led to the approval of Trastuzumab IV in the adjuvant setting (EU 2006; US ) 4,5 1. Jackisch C, et al. SABCS 2015 (Abstract PD5-01);. 2. Slamon D, et al. SABCS 2015 (Abstract S5-04); 3. Slamon D, et al. NEJM 2011; 365: (Suppl data);4. EMA. Herceptin SmPC. October 2016; 5. FDA. Herceptin PI. March 2016.

13 pcr* (%) EFS (%) Neoadjuvant and adjuvant Herceptin therapy improved pcr and EFS in after long-term follow-up NOAH 1,2 50 p = % % 10 0 With Without Herceptin Herceptin 38% p = With Herceptin 19% Chemotherapy plus Herceptin (n = 117) Chemotherapy plus Herceptin Chemotherapy HR (95% CI) = 0.64, log-rank p value = Chemotherapy (n = 118) 10 Events 49 (42%) 62 (53%) 5-year EFS (%, 58 (48 66) 43 (34 52) 0 95% CI) Without Herceptin Number at risk Mont Chemotherapy plus hs bpcr tpcr Herceptin Chemotherapy Trastuzumab IV approval in HER2-positive ebc The NOAH study led to the approval of Herceptin IV in the neoadjuvant-adjuvant setting in the EU (2012) 3 1. Gianni L, et al. Lancet 2010;375: ; 2. Gianni L, et al. Lancet Oncol 2014;15: ; 3. EMA. Herceptin SmPC. October 2016.

14 Trastuzumab revolutionized treatment for patients with HER2-positive BC 2,227,799 patients treated ~16,830 trial BC patients 1 1. PSUR (PBRER) trastuzumab, 25th Sep to 24th Sep. 2016, F. Hoffmann-La Roche Ltd, Report Number

15 Still, there are unmet needs BCIRG 006 Disease free survival Biomarker! Needs more (effective) therapy Less (toxic) therapy Slamon D,et al. Cancer Res 2016;76

16 Escalation strategy BEYOND TRASTUZUMAB

17 Increase duration of trastuzumab Goldhirsch Lancet Oncol 2013;82:1021.

18 Adding different agent -neratinib ExteNET study design HER2+ BC Prior adjuvant trastuzumab & chemotherapy LN + or residual invasive disease after NACT (N = 2840 ) R Stratification factors HR status: HR+ vs HR- LN status : 0 vs 1-3 vs 4 Adjuvant trastuzumab: sequential vs concurrent Neratinib x 1 year 240mg/day Placebo x 1 year F O L L O W - U P 2y idfs 5y idfs OS Chan et al, Lancet Oncol 2016;17:

19 Adjuvant neratinib : 5 year analysis HR 0.73 (95% CI ); p = Martine M et al, Lancet Oncol 2017;18:

20 Adjuvant neratinib : ExteNET results HR (+) 1 HR (-) Martine et al, Lancet Oncol 2017;18:

21 ExteNET : summary Adjuvant neratinib after 1 year of trastuzumab increased idfs in HR+ HER2+ BC High rates of diarrhea: G2 32%, G3 40% Intensive anti-diarrheal prophylaxis needed Adjuvant neratinib approved by US FDA in 2017 More questions than answers Why only in HR(+)? Neratinib use after neoadjuvant therapy or after pertuzumab? (non clinical trial evidence) Biomarker?

22 Adding different agent -lapatinib NeoALTTO Baselga J, et al, Lancet 2012;379:

23 Adding different agent -lapatinib ALTTO: Safety analysis AE leading to discontinuation AE leading to dose reduction AE leading to dose interruptions / delays TL T-L L T 481 (23%) 413 (20%) 945 (46%) 261 (13%) 275 (13%) 668 (32%) 317 (15%) 448 (22%) 821 (40%) 171 (8%) 81 (4%) 419 (20%) Moreno-Aspitia A et al, ASCO 2017

24 Adding different agent : pertuzumab 1. Swain S, et al. N Engl J Med 2015;372: Schneeweiss A, et al. Ann Oncol 2013;24: , 3.Gianni L, et al. Lancet Oncol 2012: 13:25-32,

25 Adding different agent -pertuzumab S U R G E R Y APHINITY (BO25126): Phase III adjuvant study Central confirmation of HER2 status (N = 4805 ) R Randomisation and treatment within 8 weeks of surgery Chemotherapy* + trastuzumab + pertuzumab Chemotherapy* + trastuzumab + placebo Anti-HER2 therapy for a total of 1 year (52 weeks) (concurrent with start of taxane) Radiotherapy and/or endocrine therapy may be started at the end of adjuvant chemotherapy * Standard anthracycline or non-anthracycline (TCH) regimens were allowed F O L L O W - U P 10 Y E A R S von Minckwitz G, et al. N Engl J Med 2017 clinicaltrials.gov/ct2/show/nct

26 APHINITY : endpoints and statistical assumptions Endpoints Primary IDFS (excluding second primary non-breast cancer tumors): Time from randomization until the date of the first occurrence of one of the following events: - Ipsilateral invasive breast tumor recurrence - Ipsilateral local-regional invasive breast cancer recurrence - Distant recurrence - Contralateral invasive breast cancer - Death attributable to any cause including breast cancer, non-breast cancer, or unknown cause Secondary IDFS: as per STEEP definition (including second non-primary BC tumors) DFS OS RFI DRFI Safety Cardiac safety (primary safety endpoint) HRQoL Statistical assumption: HR=0.75 Expected 3-year IDFS rate placebo vs pertuzumab: 89.2% vs 91.8% 379 events and 4,800 patients required for 870% power and αof 5%

27 Stratification factors by treatment Nodal status, n (%) 0 positive nodes and T 1 cm* 0 positive nodes and T >1 cm* 1 3 positive nodes 4 positive nodes Adjuvant chemotherapy regimen (randomized), n (%) Anthracycline-containing regimen Non-anthracycline-containing regimen Hormone receptor status (central), n (%) Negative (ER- and PR-negative) Positive (ER- and/or PR-positive) Protocol version, n (%) Protocol A Protocol Amendment B Pertuzumab n = (3.8) 807 (33.6) 907 (37.8) 596 (24.8) 1865 (77.7) 535 (22.3) 864 (36.0) 1536 (64.0) 1828 (76.2) 572 (23.8) Placebo n = (3.5) 818 (34.0) 900 (37.4) 602 (25.0) 1877 (78.1) 527 (21.9) 858 (35.7) 1546 (64.3) 1827 (76.0) 577 (24.0) Tumour size (cm), n (%) <2 2 < (40.8) 1275 (53.1) 147 (6.1) 948 (39.4) 1283 (53.3) 174 (7.2)

28 Proportion event-free Invasive disease free survival year 98.6% 98.8% 2 years 96.4% 95.7% 3 years 94.1% 93.2% 4 years 92.3% 90.6% Pertuzumab (n = 2400) Placebo (n = 2404) HR 0.81; 95% CI ; p = Time (months) No. of patients at risk All the contents in the presentation is owned by the speaker and does not necessarily represent the views and opinions of Roche Korea. It may contain therapies currently under clinical development for the purpose of scientific discussion and the company does not recommend any off-label uses. Physicians should refer to the approved PI before prescription

29 Proportion eventfree IDFS results: Lymph node-positive subgroup year 2 years 98.1% 94.9% 98.2% 93.7% 3 years 4 years 92.0% 89.9% 90.2% 86.7% Unstratified HR 0.77; 95% CI ; p = Time (months) No. of patients at risk All the contents in the presentation is owned by the speaker and does not necessarily represent the views and opinions of Roche Korea. It may contain therapies currently under clinical development for the purpose of scientific discussion and the company does not recommend any off-label uses. Physicians should refer to the approved PI before prescription

30 Proportion event-free IDFS results: HR-negative subgroup year 2 years 98.1% 97.9% 96.2% 93.7% 3 years 4 years 92.8% 91.0% 91.2% 88.7% Unstratified HR 0.76; 95% CI ; p = Time (months) No. of patients at risk All the contents in the presentation is owned by the speaker and does not necessarily represent the views and opinions of Roche Korea. It may contain therapies currently under clinical development for the purpose of scientific discussion and the company does not recommend any off-label uses. Physicians should refer to the approved PI before prescription

31 Patients, % Most common AEs Pertuzumab n = 2364 Placebo n = 2405 All grade Grade 3 All grade Grade 3 Diarrhoea Nausea Fatigue Arthralgia Myalgia Stomatitis Anaemia Dysgeusia <0.1 Rash Decreased appetite Mucosal inflammation Epistaxis 18.2 < Oedema peripheral Pruritus <0.1

32 Cardiac toxicity Primary cardiac, n (%) Heart failure NYHA III/IV + LVEF drop Recovered according to LVEF Cardiac death* Pertuzumab n = (0.7) 15 (0.6) 7 2 (0.08) Pertuzumab vs. placebo (95% CI) Placebo n = (0.0, 0.8) 8 (0.3) 6 (0.2) 4 2 (0.08) Secondary cardiac** Identified from LVEF assessments Identified by CAB 64 (2.7) 50 (2.1) 14 (0.6) -0.1 (-1.0, 0.9) 67 (2.8) 47 (2.0) 20 (0.8) Note: one death due to heart failure occurred in the Trastuzumab arm All the contents in the presentation is owned by the speaker and does not necessarily represent the views and opinions of Roche Korea. It may contain therapies currently under clinical development for the purpose of scientific discussion and the company does not recommend any off-label uses. Physicians should refer to the approved PI before prescription

33 De-escalation strategy LESS IS MORE

34 Adjuvant Paclitaxel and Trastuzumab for nodenegative HER2 positive breast cancer S U R G E Tumor 3cm Node negative HER2 positive BC (N = 406 ) Weekly paclitaxel 80mg/m 2 + trastuzumab 4mg/kg D1 2mg/kg for 12 weeks Trastuzumab 2mg/kg weekly or 6mg/kg every 3 weeks for 40 weeks R Y Tolaney SM et al. N Engl J Med 2015;372:

35 Disease-free and recurrence-free survival, APT 3yr idfs: 98.7% DFS events at 7 years Any recurrence or death Local/Regional recurrence N 23 (5.7%) 5 (1.2%) Ipsilateral axilla 3 Ipsilateral breast 2 New contralateral primary breast cancer 6 (1.5%) HER2+ 1 HER2-3 Her2 unknown 2 Distant recurrence 4 (1.0%) Non breast cancer related death 8 (2.0%) Tolaney SM et al. N Engl J Med 2015;372: , Tolaney ASCO 2017.

36 Docetaxel/cyclophosphamide/Trastuzumab for early stage HER2+ BC Stage 1-2 HER2+ BC (N = 493) Docetaxel Cyclophosphamide Trastuzumab Trastuzumab F O L L O W - U P 2y idfs 2 year DFS: 97.8% (95% CI: ) 2 year OS; 99.5% (95% CI: ) Excellent outcome in both TOP2A amplified & nonamplified patients Jones SE et al, Lancet Oncol 2013.

37 ATEMPT trial Stage 1 HER2+ BC ER+ or ER- PS 0-1 Adequate organ fx (N = 500 ) R T-DM1 q 3 weeks x 17 Paclitaxel + Trastuzumab x 12 Trastuzumab q 3 weeks x 13 F O L L O W - U P DFS All the contents in the presentation is owned by the speaker and does not necessarily represent the views and opinions of Roche Korea. It may contain therapies currently under clinical development for the purpose of scientific discussion and the company does not recommend any off-label uses. Physicians should refer to the approved PI before prescription

38 SOLD PHARE Short-HER Hellenic Group Persephone HERA Duration of trastuzumab Chemo Backbone Duration N DFS HR PHARE 1 Investigator choice 6 mos % (48m) 1.28 ( ) 12 mos % Short-HER 2 TH#3-FEC#3 9 weeks % 1.15 ( ) AC/FEC#4-TH#4-H 12 mos % SOLD 3 TH#3-FEC#3 9 wks % (5y) 1.39 TH#3-FEC#3-H 12 mos % Hellenic ddfec-t 6 vs 12 group 4 months % vs 95.7% (3yr) 1.57 ( ) Persephone 5 Investigator choice 6 vs 12 months Pivot X, et al, Lancet Oncol 2013;14: NCT SABCS Mavroudis D, e al. Ann Oncol NCT

39 Results: SOLD trial Joensuu H, et al. SABCS 2017

40 Subset analyses : SOLD trial Joensuu H, et al. SABCS 2017

41 Duration of trastuzumab 12 months of adjuvant trastuzumab : standard Selected group of patients may benefit from shorter duration Low disease burden HR positive Cardiac risk factors

42 Surgery Randomised, open-label, Phase III, non-inferiority study to compare the pharmacokinetics, efficacy and safety of Herceptin SC and IV in HER2-positive early breast cancer Herceptin SC HER2-positive early breast cancer (N=596) R 1:1 Herceptin IV Follow-up: 5 years 2 Herceptin SC Fixed dose of 600 mg (5 ml over 5 minutes) Herceptin IV 8 mg/kg loading dose; 6 mg/kg maintenance dose Docetaxel 75 mg/m 2 FEC 500/75/500 1 year (18 cycles) Herceptin Safety, tumour response pcr Safety, EFS, OS Pharmacokinetics Primary endpoint Show non-inferiority of SC vs. IV based on co-primary endpoints Pharmacokinetics: observed Herceptin C trough pre-dose Cycle 8 (pre-surgery) Efficacy: pcr in the breast EFS, event-free survival; FEC, 5-fluorouracil+epirubicin+cyclophosphamide; IV, intravenous; pcr, pathological complete response; OS, overall survival; SC, subcutaneous 1. Ismael G, et al. Lancet Oncol 2012; 2.

43 Estimated probability HannaH: Similar EFS rates seen with Herceptin SC and IV (ITT population) EFS rates 3 years after randomisation: Herceptin SC: 76% Herceptin IV: 73% (HR 0.95; 95% CI = 0.69; 1.30) Randomised treatment Herceptin IV Herceptin SC N at risk Herceptin IV Herceptin SC Months months treatment-free follow-up CI, confidence interval; EFS, event-free survival; HR, hazard ratio; ITT, intent-to-treat; IV, intravenous; SC, subcutaneous Jackisch C, et al. St. Gallen 2015 (Poster P201)

44 Efficacy and safety of subcutaneous or intravenous trastuzumab in patients with HER2-positive early breast cancer after 5 years treatment-free follow-up: Final analysis from the phase III, open-label, randomized HannaH study Overview The HannaH study has shown that Herceptin SC has a comparable safety and efficacy profile to that of Herceptin IV in HER2-positive ebc 1 This long-term follow-up analysis evaluates whether the benefit seen with Herceptin SC continues after treatment stops, as is the case with Herceptin IV, and also the potential relationship between tpcr and long-term outcomes The overall safety profile of Herceptin SC after long-term follow-up is also evaluated Results Baseline characteristics including nodal status, hormone receptor status, tumour size and whether the disease was locally advanced were balanced across both arms Overall rates of any grade, Grade 3 or cardiac AEs were similar in the two study arms More serious AEs were observed with H SC than H IV (21.9% vs. 15.1%) Data in context 6-year EFS Rate, (95% CI) 6-year EFS by tpcr status* Rate, (95% CI) 6-year OS Rate, (95% CI) H SC n = ( ) tpcr 0.82 ( ) 0.83 ( ) no tpcr 0.54 ( ) 0.57 ( ) n = ( ) Comparable efficacy was observed across all subgroups Hazard ratio H IV (95% CI) n = ( ) 0.98 ( ) n = ( ) 0.94 ( ) The non-inferiority of Herceptin SC compared with IV was confirmed after long-term follow-up, with no new safety signals being reported The results also add to the evidence that there is a positive association between tpcr and more favourable long-term outcomes 2 in HER2-positive ebc 3 A notable proportion of patients experience disease recurrence despite neoadjuvant therapy, and so more advanced treatment options are still needed Herceptin SC is being investigated in combination with PERJETA SC as part of the breast cancer development programme (Phase Ib data presented at SABCS P ) Jackisch C, et al. Abstract PD3-11 * Efficacy per-protocol population 1. Ismael G, et al. Lancet Oncol 2012; 2. Cortazar P, et al. Lancet Gianni L, et al. Lancet Oncol 2016

45 HER2 positive BC: from the most deadly disease to most treatable form of breast cancer Adjuvant 2017 Pertuzumab Adjuvant Neratinib Trastuzumab SC T-DM1 for MBC Neoadjuvant Pertuzumab Discovery of HER Trastuzumab for MBC firstline 2007 Lapatinib for ABC Trastuzumab For EBC adjuvant 2012 Pertuzumab for MBC

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47 Preoperative/Adjuvant therapy regimens for HER2-positive BC, NCCN guideline 2018 Preferred regimens: AC followed by T + trastuzumab AC followed by T + trastuzumab + pertuzumab Paclitaxel + trastuzumab TCH TCH + pertuzumab Useful in certain circumstances Docetaxel + cyclophosphamide + trastuzumab Other recommended regimens AC followed by docetaxel + trastuzumab AC followed by docetaxel + trastuzumab + pertuzumab

48 Patients cannot benefit from the treatment they did not receive! Indication Korea Japan Thailand Hong Kong Taiwan Singapore Philippines Indonesia Malaysia China T_DM1 MBC; Monotherapy Reimburs ement Reimburs ement None None None None None None None None Pertuzu mab HER-2 (+) MBC Treatment in Combination with trastuzumab & docetaxel Reimburs ement Reimburs ement Reimbur sement Reimburse ment None None None None None None Neo adjuvant None not identifi ed None None None None None None None None MBC Reimburs ement Reimburs ement None Reimburse ment Reimbu rsement None None Reimburse ment None Reimbu rsement Trastuz umab Neoadjuvant Reimburs ement Reimburs ement Reimbur sement Reimburse ment Reimbu Reimburs rsement ement Reimburse ment None Reimbur sement Reimbu rsement Adjuvant Reimburs ement Reimburs ement Reimbur sement Reimburse ment Reimbu Reimburs rsement ement Reimburse ment None Reimbur sement Reimbu rsement

49 Biomarkers to predict response to anti- HER2 therapy HER2 mrna expression, FISH ratio, protein expression, HER2 CTC, HER2 ECD PIK3CA mutation ER positivity Intrinsic subtypes TILs Immune signatures

50 Biomarkers to predict response to anti- HER2 therapy HER2 : Higher pcr PIK3CA mutation: Lower pcr ER positivity: Lower pcr HER2 enriched subtype: Higher pcr Currently there are no reliable biomarker to predict benefit from anti-her2 treatment in the adjuvant setting! Please visit overcoming resistance to HER2-directed therapies presentation by Dr. Ian Krop

51 Using response to neoadjuvant therapy as biomarker pcr is predictive of EFS and DRFS : I-SPY2 TRIAL EFS HR-HER2+ DRFS Yee D, et al. San Antonio Breast Cancer Symposium, Dec 5-9, 2017

52 Neoadjuvant trials as platform of testing novel escalation/de-escalation strategy Experimental therapy De-escalation pcr Neoadjuvant therapy Non-pCR Standard therapy Experimental therapy - escalation Please visit plenary session 1 by Dr. Eric Winer Standard therapy

53 What next? Escalation Combination with CDKi Combination with IO Combination with mtor inhibitor/pi3k inhibitor De-escalation Biologics only Combination with endocrine therapy We need robust biomarker to select therapy!

54 Ongoing clinical Trials of Anti-HER2 S. Parakh et al. Cancer Treatment Reviews 59(2017) 1-21

55 Ongoing clinical Trials of Immune Checkpoints Inhibitors in HER2+ BC Please visit overcoming resistance to HER2-directed therapies presentation! Prof SB.Kim L. De la Cruz-Merino et al. International Review of Cell and Molecular Biology 331 (2017) 1-53

56 Kaitlin : study schema Curative surgery HER2 positive LN positive or >2cm (n=1846) R FEC AC EC FEC AC EC T-DM1 + Pertuzumab Taxane + Trastuzumab + pertuzumab IDFS IDFS in LN(+)

57 Katherine : study schema Preoperative therapy Taxane ± Anthracycline (n=1484) Residual tumor T-DM1 Trastuzumab 3 year IDFS

58 Summary One year of trastuzumab standard adjuvant treatment in ebc Extended neratinib reduce recurrence in HR+HER2+ higher risk BC Pertuzumab improves DFS but only in Node positive BC Many escalation and de-escalation strategies are ongoing to improve efficacy/reduce toxicity of adjuvant treatment HER2+ EBC Biomarker to identify those who need more/less therapy is eagerly awaited

59 Hur!