Adjuvant Chemotherapy TNBC & HER2 Subtype

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1 Adjuvant Chemotherapy TNBC & HER2 Subtype Gun Min Kim Yonsei Cancer Center Division of Medical Oncology Department of Internal Medicine Yonsei University College of Medicine

2 Contents HER2 양성유방암 Chemotherapy Indication & Regimen Herceptin 보험급여유의사항 삼중음성유방암 Chemotherapy Indication & Regimen 보험급여유의사항

3 HER2+ BREAST CANCER

Indication T 0.5 cm: No adjuvant chemotherapy T 0.6 1.

4 Indication T 0.5 cm: No adjuvant chemotherapy T cm: Consider adjuvant chemotherapy with Herceptin (IIA) T > 1 cm or Node (+): Adjuvant chemotherapy with Herceptin (I) Node (-) 0.5cm cm No adjuvant CTx or Herceptin Consider adjuvant CTx + Herceptin Node (+) > 1.0cm Adjuvant CTx + Herceptin

5 Learning Points Chemotherapy regimen Anthracycline vs. Non-anthracycline Duration of Herceptin 6 months vs. 1 year vs 2 year Cardiac monitoring Small (<1cm) HER2+ Tumor

6 Choice of Chemotherapy Regimen Chemotherapy Regimen Anthracycline-based: AC#4 Taxane#4 + H 1Y Non-anthracycline-based: TCH#6 H 1Y NSABP B31 1 (n=2043) N (n=1633) HERA 2 (n=5081) BCIRG (n=3222) FINHER 4 (n=1010) A AC#4 Paclitaxel #4 AC#4 Paclitaxel#4 H Observat ion AC#4 Docetaxel#4 Docetaxel#3 FEC#3 ± H B AC#4 Paclitaxel #4 +H AC#4 Paclitaxel#4 H 1 Yr of H AC#4 Docetaxel#4 + H Vinorelbine#3 FEC#3 ± H C AC#4 Paclitaxel#4 + H 2 Yr of H Docetaxel+Carbo platin#6 + H 1. N Engl J Med 2005;353: N Engl J Med 2005;353: N Engl J Med 2011;365: N Engl J Med 2006;354:809-20

7 Cardiac Risk Assessment J Clin Oncol 30: , 2012

8 B-31: Risk Factors for CHF

9 Cardiac Monitoring Algorithm Suter T M et al. JCO 2007;25:

10 Duration of Herceptin 3P (Payer/Patient/Physician) vs. Roche 1 year vs. 2 years: HERA 1 1 year vs. 6 months: PHARE 2 1. Lancet 2013; 382: Lancet Oncol 2013; 14:

11 HERA (Median f/u of 8 years) 2Y is not superior to 1Y 1Y of Herceptin: Clear DFS and OS benefit Standard of Care Lancet Oncol 2013; 14:

12 PHARE (Non-Inferior Study) Median 3.5 year f/u: Fail to show 6M is not inferior to 12M Despite the higher rates of cardiac events, 12M Standard of Care * Cardiac Event 12M vs. 6M 5.7% vs. 1.9% (p<0.001) Lancet Oncol 2013; 14:

13 BCIRG 006

14 BCIRG-006 (Anthracycline vs. Non-anthracycline) The risk benefit ratio: TCH > AC-TH Similar Efficacy & Fewer Toxicity 급여적용은 LN positive 만가능 N Engl J Med 2011;365:

15 Small (<1cm) HER2+ Tumors N=965, 10% HER2+ tumors No chemotherapy or trastuzumab

16 pt1a/bn0 HER2+ Breast Cancer Outcomes THE AMERICAN JOURNAL OF HEMATOLOGY/ONCOLOGY 2014 Vol 11. No1

17 Benefits of Herceptin in pt1a/bn0 Breast Cancer THE AMERICAN JOURNAL OF HEMATOLOGY/ONCOLOGY 2014 Vol 11. No1

18 APT trial Single arm, Phase II study N=410, Node(-) T<3cm HER2+ BC Anthracycline-free regimen Weekly HP#12 H 9m 3Y DFS rate: 98.7% CHF incidence: 0.5% NEJM 2015 JAN 372;2

19 보험급여기준 T 0.5 cm: No adjuvant chemotherapy or Herceptin pn1mi: Node (+) 로 Herceptin 급여청구가능 T cm: Consider adjuvant chemotherapy with Herceptin ( 비급여 ) Adjuvant chemotherapy Herceptin ( 비급여 ) 1Y T > 1 cm or Node (+): Adj CTx with Herceptin 1Y Adjuvant chemotherapy Herceptin 1Y AC#4 TH#4 H#14 TCH#6 H#12 (Node+ 만급여 ) * Adjuvant Herceptin( 급여 ) 1Y 을사용하기위해서는항암치료를반드시시행해야함. * Adjuvant Taxane+Herceptin 을사용하기위해서는 AC#4 를반드시시행해야함.

20 Herceptin SC 적응증 유방암에서 IV Herceptin 과동일한적응증으로허가됨 용량 : Fixed dose 600mg 투여방법 3-5 분간허벅지에피하주사 비용 130 만원 /Vial 50kg 이상의경우 IV 보다저렴 55kg: IV 2700 만원 vs. SC 2300 만원 45kg: IV 1850 만원 vs. SC 2300 만원

21 HannaH Trial

22 Other Targeted Therapy Bevacizumab: No benefit Lapatinib: No significant benefit Currently ongoing trials Pertuzumab: APHYNITY T-DM1: KATHERINE, KAITLIN

23 Summary (HER2+ BC) Chemotherapy Regimen AC#4 followed by Taxane+Herceptin#4 TCH (Docetaxel+Carboplatin+Herceptin)#6 Duration of Herceptin: 1Y 3 개월간격 cardiac function monitoring Node(-) Small Tumor ( 1cm) Risk-Benefit 고려 ( 특히 poor risk feature (1cm size, high histologic grade, HR-, young age 등 ) 가진경우 보험급여기준 T cm: Herceptin ( 비급여 ) T > 1 cm or Node (+): Adjuvant CTx with Herceptin 1Y AC#4 TH#4 TCH#6 (Node+ 만급여 ) Herceptin SC 허가됨

24 TRIPLE NEGATIVE BREAST CANCER

25 Indication T < 0.5 cm: No adjuvant chemotherapy T cm: Consider adjuvant chemotherapy (IIA) T > 1 cm or Node (+): Adjuvant chemotherapy (I) 0.5cm No adjuvant CTx Node (-) cm Consider adjuvant CTx > 1.0cm Regimen?? Node (+) Adjuvant CTx

26 Adjuvant Chemotherapy Regimen No single standard regimen in BC Anthracycline-based Taxane CMF AC TC FAC FEC AC T TAC FEC T AC wp ddac T CMF AC < TC TAC AC/FEC T < ddac wp

27 Learning Points Chemotherapy regimen Anthracycline (Doxorubicin vs Epirubicin) Taxane (Paclitaxel vs Docetaxel) TC / TAC Dose-dense regimen Others Bevacizumab PARP inhibitor

28 Anthracyclines Doxorubicin-based AC (60/600) FAC (500/50/500) Epirubicin-based EC (90/600) FEC (600/90/600, 500/100/500) * AC T regimen 은현재 AC 용법을사용해야만보험급여적용이됨

29 Paclitaxel vs Docetaxel ECOG 1199 N=4950, Node(+) or high-risk Node(-) T2/3N0 2X2 Factorial design AC Paclitaxel Q3W AC Weekly Paclitaxel AC Docetaxel Q3W AC Weekly Docetaxel J Clin Oncol :

30 ECOG 1199 Long-Term Result All Population TNBC subtype J Clin Oncol :

31 TC vs. AC US Oncology 9735 N=510, TC#4 vs. AC#4 T 1cm~7cm N0 50%, N1 40%, N2 10% J Clin Oncol :

32 TAC vs. FAC BCIRG N=1491, Node (+) BC T4, N3 제외 GEICAM N=1060, High-risk Node(-) BC T >2cm, ER/PR-, HG 2 or 3, Age<35 TAC#6 (75/50/500) vs. FAC#6 (500/50/500) 1. Lancet Oncol Jan;14(1): N Engl J Med Dec 2;363(23):

33 Adjuvant TAC BCIRG 001 GEICAM 9805

34 TNBC subgroup (GEICAM 9805) Lancet Oncol Jan;14(1):72-80.

35 Dose-dense Chemotherapy Dose-dense(DD) regimen DD AC: AC (60/600) 2주간격 DD EC: EC (90/600) 2주간격 DD Paclitaxel: Paclitaxel 175mg/m 2 2주간격 Weekly Paclitaxel: Paclitaxel 80mg/m 2 DD regimen vs. Conventional Tx CALGB GIM Phase III 2 1. J Clin Oncol (8): Lancet 2015; 385:

36 DD Regimen in Adjuvant Setting CALGB 9741 GIM Phase III Lancet 2015; 385:

37 DFS of DD Regimen by Subtype ER(+) Patients ER(-) Patients Lancet 2015; 385:

38 Meta-analysis of DD regimen All Patients ER+ Patients (HR 0.93, 95% CI ) P=0.25 ER(-) Patients Breast Cancer Res Treat (2015) 151:

39 Prophylactic G-CSF in DD AC Filgrastim AC 항암치료 48 시간이후시작하여 daily G-CSF 투여 (ANC 가 nadir 지나서회복될때까지 ) 단점 : Real practice 에서적용하기어려움, ANC 500 이상인경우비보험 Peg-filgrastim AC 항암치료 24 시간이후에한번투여 단점 : 90 만원 /V 의고가, 비보험 Neulasta: original Neulapeg, Dulastin: generic (60 만원 /V)

40 Risk of hospitalization according to chemotherapy regimen SEER/Texas Cancer Registry N=9327 EBC, J Clin Oncol Jul 1;32(19)

41 보험급여기준 T 0.5 cm: No adjuvant chemotherapy pn1mi: Node (+) 로청구가능 T cm: Consider adjuvant chemotherapy AC#4, FAC#6, CMF#6 T > 1 cm or Node (+): Adjuvant chemotherapy Node (+) BC : AC#4 T#4, TAC#6, TC#4 Node (-) BC T > 1cm: AC#4, TC#4 (T 1~7cm) T2/3N0: AC#4 weekly paclitaxel#12 High-risk (T > 2cm or 35 세미만 or HG 2-3 or TNBC): TAC#6 Dose dense regimen 사용은급여청구에문제없음

42 Other Therapy Bevacizumab: No benefit Platinum: No data Currently ongoing trials PARP inhibitor: OlympiA (BRCA+)

43 Summary (TNBC) Chemotherapy Indication T 0.5 cm: No adjuvant chemotherapy T cm: Consider adjuvant chemotherapy (IIA) T > 1 cm or Node (+): Adjuvant chemotherapy (I) Chemotherapy Regimen ( 급여조건 ) Node (-): AC#4, CMF#4 T2/3N0: AC->weekly paclitaxel T 1~7cm: TC#4 High-risk (T > 2cm or 35 세미만 or HG 2-3 or TNBC): TAC#6 Node (+): AC#4 T#4, TAC#6, TC#4 Dose-dense regimen 사용가능 (with prophylactic G-CSF) Others Bevacizumab: No role in adjuvant setting Platinum: Benefit in neoadjuvant setting, Adjuvant role? PARP inhibitor: Current investigating

44 CASE 1 F/35 EBC s/p PM c SLNB IDC 0.8cm, LN 0/7 N3H3, LVI (+) ER/PR/HER2 -/-/3+ pt1n0 Adjuvant therapy? High risk group consider adjuvant chemotherapy + Herceptin

45 CASE 2 F/55 Adjuvant Herceptin 치료중 EF 감소 Baseline EF=55% 6 Cycle 후 EF=45% No CHF symptoms Next Plan? Herceptin 일시중단하고 3 주후재평가 EF 회복하면재투여고려

46 CASE 3 F/40 EBC s/p PM c ALND IDC 2.2cm, LN 2/7 N3H3, ER/PR/HER2 -/-/- pt2n1 Adjuvant chemotherapy regimen? AC T vs. TAC Weekly paclitaxel vs. docetaxel q3w Dose dense vs. standard

47 감사합니다.

EARLY STAGE BREAST CANCER ADJUVANT CHEMOTHERAPY. Dr. Carlos Garbino

EARLY STAGE BREAST CANCER ADJUVANT CHEMOTHERAPY Dr. Carlos Garbino EARLY BREAST CANCER ADJUVANT CHEMOTHERAPY SUSTANTIVE DIFFICULTIES FOR A WORLDWIDE APPLICABILITY DUE TO IMPORTANT INEQUALITIES + IN DIFFERENT