St Gallen 2017 controversies & consensus

Transcription

1 St Gallen 2017 controversies & consensus Shani Paluch-Shimon, MBBS, MSc Head, Breast Cancer Service for Young Women Breast Unit, Division of Oncology Sheba Medical Centre June 2017

2 St Gallen 2017 De-escalation vs Escalation Defining risk groups

3 HER2+

4 HER2+ Do the majority of LN-negative need anti- HER2 therapy when: pt1a pt1b pt1c Yes 33% 86% 94% No 63% 10% 0%

5 In LN-negative, is TH a reasonable option in the following 1. pt <1cm 2. pt - 1-2cm 3. pt 2-3cm

6 HER2+ In LN-negative, is TH a reasonable option? Yes-92% No - 4% In LN-negative, is TH a reasonable option in the following: pt <1cm pt - 1-2cm pt 2-3cm Yes 89% 79% 50% No 10% 15% 44%

7 TH Tolaney et al <50-32% T2 (2-3cm) 8.9% N0 98.5% N1mic-1.5% HR+ - 67%

8 Invasive Disease-Free Survival Tolaney et al, ASCO 2017

9 NAST in HER2+ in Stage II-III If eligible for BCS, should patient preferably receive NAST? 1. Yes 2. No 3. Abstain

10 NAST in HER2+ in Stage II-III If eligible for BCS, should patient preferably receive NAST? Yes 94% No-4%

11 NAST in HER2+ in Stage II-III Is it acceptable to give TH only (meaning: any chemorx + H without Pertuzumab? 1. Yes 2. No 3. Abstain

12 NAST in HER2+ in Stage II-III An acceptable regimen would include THP (meaning: any chemorx + HP)? 1. Yes 2. No 3. Abstain

13 NAST in HER2+ in Stage II-III Is it acceptable to give TH only (meaning: any chemorx + H without Pertuzumab): Yes 35% No 57% An acceptable regimen would include THP (meaning: any chemorx + HP): Yes 84% No-8%

14 pcr, % 95% CI NeoSphere: Superior pcr from addition of Pertuzumab to standard Trastuzumab/Docetaxel p = p = p = % % 16.8% TH THP HP TP Treatment 24.0% 29% in ERsubgroup

15 PFS (%) PFS (%) NeoSphere: Increased pcr rates were associated with improved PFS PFS at 5-year follow-up analysis % 81% PHT Overall population 5-year PFS, % (95% (95% CI) No tpcr (n = 323) tpcr (n = 94) 76 (71 81) 85 (76 91) % 5-year PFS with PHT HT 20 Stratified HR = 0.54 (95% CI = ) Time (months) Time (months) Gianni L, et al. Lancet Oncol 2016; 17:

16 BERENICE - pcr showed clinical benefit for pertuzumab with trastuzumab in combination with either ddac or FEC-D

17 Following NAST with chemotherapy + HP, should patients complete a year of Herceptin AND Pertuzumab? 1. Yes 2. No 3. Abstain

18 % Event -free % Event -free Unmet medical need remains in HER2+ EBC Adjuvant 1 HERA Disease-free survival Neoadjuvant 2 NOAH Event-free survival % % Without H HR=0.76 (95% CI: ) P< With H Without H HR=0.64 (95% CI: ) P=0.016 With H tpcr Chemo + trast 38% Chemo only 19% Years from randomisation Years from randomisation 1. Goldhirsch, et al. Lancet 2013 (suppl.); 2. Gianni, et al. Lancet Oncol 2014

19 Triple negative breast cancer

20 TNBC Should platinum based regimens be considered in all Stage II-III TNBC? Yes 10% No-86% Should platinum be considered only if known BRCA mutation? Yes 47% No-43% Can we avoid chemotherapy in pt1an0? Yes 78% No-20% Should dose dense Rx be preferred in TNBC? Yes 37% No 55%

21 TNBC Neo-adjuvant treatment If BRCA - negative, should the treatment regimen include a platinum AND alkylating agent? (for example AC-TCarbo) 1. Yes 2. No 3. Abstain

22 TNBC Neo-adjuvant treatment If BRCA - positive, should the treatment regimen include a platinum AND alkylating agent? (for example AC-TCarbo) 1. Yes 2. No 3. Abstain

23 TNBC Neo-adjuvant treatment Should the approach whether or not to give platinum differ between the adjuvant & neo-adjuvant setting? 1. Yes 2. No 3. Abstain

24 NAST in TNBC In TNBC, NAST: Yes No Irrespective of BRCA status, Rx regimen should include a platinum OR alkylating agent The preferred regimen should include an anthracycline & taxane 71% 75% 15% 12%

25 GeparSixto GEICAM Japanese study CALGB Phase II St II-III TN N=164 gbrca Ph II St II-III TN N=94 PhII St II-III TN N=75 PhII St II-III TN N=443 Platinum agents - Only data in Neo-adjuvant PegDox-T-Bev vs Peg-Dox-T-Bev- Carbo EC-Txt vs EC- TxtCb T-FEC vs TCb-FEC AC-T AC-TBev AC-TCb AC-TCbBev pcr pcr (ypt0/isn0) 36.9% vs 53.2% HR 1.52 (1.04, 2.29) 50% vs 61.5% (p=0.4) 26.3% vs 61.2% (SS) pcr (yt0) Primary end point Bev 59% vs 48% (ss) Cb 60% vs 46% (ss) Bev&Cb 67% (sig) pcr (yt0n0) Secondary end point Bev 52% vs 44% (ns) Cb 54% vs 41% (ss) Bev&Cb 60% (sig) Rx discontinuation carbo AUC % pcr in mbrca (n=50) HR1.6 (0,.42,4.93) NO convincing No difference or consistent data about platinum: in wtbrca vs mbrca - Outcome benefit - Improvements in eligibility for BCS - NS Outcome DFS HR 0.56(0.33,0.96) Addition of Carbo: EFS HR 0.84 (0.58,1.22) OS 1.15 (0.74, 1.79) Addition of Bev: EFS HR 0.80 (0.55,1.17) OS 0.76 (0.49,1.19)

26 Post-NAST Adjuvant Rx in TNBC If there s residual disease of >1cm +/- LN+, following N/A AC-T, you should propose: 1. No treatment 2. Capecitabine 3. Platinum 4. Platinum if BRCA+ 5. Metronomic Rx

27 Post-NAST Adjuvant Rx in TNBC If there s residual disease of >1cm +/- LN+, following N/A AC-T, you should propose: No Rx 31% Capecitabine 49% Platinum 7% Platinum if BRCA+ - 9% Metronomic Rx 4%

28 CREATE-X

29 N=910 Her2-neg, clinically Stage I-IIIB, residual disease in the breast or lymph nodes, after NAST containing anthracycline &/or taxane Randomized to Capecitabine vs Control

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33 What will guide escalation/deescalation in the future?

34 Classic clinico-pathological characteristics Molecular/genomic profiles Targeted agents Toxicity profiles Patient related factors co-morbidities, preference

35 Characteristics of Residual Disease post-neoadjuvant chemotherapy Presented By Carey Anders at 2016 ASCO Annual Meeting

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37 Editors-in-chief: Nadia Harbeck Christian Thomssen Michael Gnant On behalf of the editorial board: Invitation to submit papers 37