Adjuvant Chemotherapy TNBC & HER2 Subtype 2015.08.15 Gun Min Kim Yonsei Cancer Center Division of Medical Oncology Department of Internal Medicine Yonsei University College of Medicine gmkim77@yuhs.ac
Contents HER2 양성유방암 Chemotherapy Indication & Regimen Herceptin 보험급여유의사항 삼중음성유방암 Chemotherapy Indication & Regimen 보험급여유의사항
HER2+ BREAST CANCER
Indication T 0.5 cm: No adjuvant chemotherapy T 0.6 1.0 cm: Consider adjuvant chemotherapy with Herceptin (IIA) T > 1 cm or Node (+): Adjuvant chemotherapy with Herceptin (I) Node (-) 0.5cm 0.6-1.0cm No adjuvant CTx or Herceptin Consider adjuvant CTx + Herceptin Node (+) > 1.0cm Adjuvant CTx + Herceptin
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
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) N9831 1 (n=1633) HERA 2 (n=5081) BCIRG-006 3 (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;353:1673-84 2. N Engl J Med 2005;353:1659-72 3. N Engl J Med 2011;365:1273-83 4. N Engl J Med 2006;354:809-20
Cardiac Risk Assessment J Clin Oncol 30:3792-3799, 2012
B-31: Risk Factors for CHF
Cardiac Monitoring Algorithm Suter T M et al. JCO 2007;25:3859-3865
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: 1021 28 2. Lancet Oncol 2013; 14: 741 48
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: 741 48
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: 741 48
BCIRG 006
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;365:1273-83.
Small (<1cm) HER2+ Tumors N=965, 10% HER2+ tumors No chemotherapy or trastuzumab
pt1a/bn0 HER2+ Breast Cancer Outcomes THE AMERICAN JOURNAL OF HEMATOLOGY/ONCOLOGY 2014 Vol 11. No1
Benefits of Herceptin in pt1a/bn0 Breast Cancer THE AMERICAN JOURNAL OF HEMATOLOGY/ONCOLOGY 2014 Vol 11. No1
APT trial Single arm, Phase II study N=410, 2007-2010 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
보험급여기준 T 0.5 cm: No adjuvant chemotherapy or Herceptin pn1mi: Node (+) 로 Herceptin 급여청구가능 T 0.6 1.0 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.
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
HannaH Trial
Other Targeted Therapy Bevacizumab: No benefit Lapatinib: No significant benefit Currently ongoing trials Pertuzumab: APHYNITY T-DM1: KATHERINE, KAITLIN
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 0.6 1.0 cm: Herceptin ( 비급여 ) T > 1 cm or Node (+): Adjuvant CTx with Herceptin 1Y AC#4 TH#4 TCH#6 (Node+ 만급여 ) Herceptin SC 허가됨
TRIPLE NEGATIVE BREAST CANCER
Indication T < 0.5 cm: No adjuvant chemotherapy T 0.6 1.0 cm: Consider adjuvant chemotherapy (IIA) T > 1 cm or Node (+): Adjuvant chemotherapy (I) 0.5cm No adjuvant CTx Node (-) 0.6-1.0cm Consider adjuvant CTx > 1.0cm Regimen?? Node (+) Adjuvant CTx
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
Learning Points Chemotherapy regimen Anthracycline (Doxorubicin vs Epirubicin) Taxane (Paclitaxel vs Docetaxel) TC / TAC Dose-dense regimen Others Bevacizumab PARP inhibitor
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
Paclitaxel vs Docetaxel ECOG 1199 N=4950, 1999-2002 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 2015 33:2353-2360.
ECOG 1199 Long-Term Result All Population TNBC subtype J Clin Oncol 2015 33:2353-2360.
TC vs. AC US Oncology 9735 N=510, 1997-2000 TC#4 vs. AC#4 T 1cm~7cm N0 50%, N1 40%, N2 10% J Clin Oncol 2009 27:1177-1183
TAC vs. FAC BCIRG 001 1 N=1491, 1997-1999 Node (+) BC T4, N3 제외 GEICAM 9805 2 N=1060, 1999-2003 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. 2013 Jan;14(1):72-80. 2. N Engl J Med. 2010 Dec 2;363(23):
Adjuvant TAC BCIRG 001 GEICAM 9805
TNBC subgroup (GEICAM 9805) Lancet Oncol. 2013 Jan;14(1):72-80.
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 9741 1 GIM Phase III 2 1. J Clin Oncol 2003 21(8):1431 1439. 2. Lancet 2015; 385: 1863 72
DD Regimen in Adjuvant Setting CALGB 9741 GIM Phase III Lancet 2015; 385: 1863 72
DFS of DD Regimen by Subtype ER(+) Patients ER(-) Patients Lancet 2015; 385: 1863 72
Meta-analysis of DD regimen All Patients ER+ Patients (HR 0.93, 95% CI 0.82 1.05) P=0.25 ER(-) Patients Breast Cancer Res Treat (2015) 151:251 259
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)
Risk of hospitalization according to chemotherapy regimen SEER/Texas Cancer Registry N=9327 EBC, 2003-2007 J Clin Oncol. 2014 Jul 1;32(19)
보험급여기준 T 0.5 cm: No adjuvant chemotherapy pn1mi: Node (+) 로청구가능 T 0.6 1.0 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
Other Therapy Bevacizumab: No benefit Platinum: No data Currently ongoing trials PARP inhibitor: OlympiA (BRCA+)
Summary (TNBC) Chemotherapy Indication T 0.5 cm: No adjuvant chemotherapy T 0.6 1.0 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
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
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
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
감사합니다.