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Adjuvant Chemotherapy TNBC & HER2 Subtype
Gun Min Kim Yonsei Cancer Center
Division of Medical Oncology Department of Internal Medicine
Yonsei University College of Medicine [email protected]
2015.08.15
mailto:[email protected]�
Contents
• HER2 양성 유방암 – Chemotherapy Indication & Regimen – Herceptin – 보험 급여 유의사항
• 삼중 음성 유방암
– Chemotherapy Indication & Regimen – 보험 급여 유의사항
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 (-)
Node (+)
≤ 0.5cm
0.6-1.0cm
> 1.0cm
No adjuvant CTx or Herceptin
Consider adjuvant CTx + Herceptin
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 (
Choice of Chemotherapy Regimen
• Chemotherapy Regimen – Anthracycline-based: AC#4 Taxane#4 + H 1Y – Non-anthracycline-based: TCH#6 H 1Y
NSABP B311 (n=2043)
N98311 (n=1633)
HERA2 (n=5081)
BCIRG-0063 (n=3222)
FINHER4 (n=1010)
A AC#4 Paclitaxel #4
AC#4 Paclitaxel#4 H
Observation
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+Carboplatin#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: HERA1 • 1 year vs. 6 months: PHARE2
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
Lancet Oncol 2013; 14: 741–48
* Cardiac Event 12M vs. 6M 5.7% vs. 1.9% (p
BCIRG 006
BCIRG-006 (Anthracycline vs. Non-anthracycline)
• The risk–benefit ratio: TCH > AC-TH • Similar Efficacy & Fewer Toxicity • 급여적용은 LN positive만 가능
N Engl J Med 2011;365:1273-83.
Small (
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
보험급여 기준
• T ≤ 0.5 cm: No adjuvant chemotherapy or Herceptin – pN1mi: Node (+)로 Herceptin 급여 청구 가능
• 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+만 급여)
* Adjuvant Herceptin(급여) 1Y 을 사용하기 위해서는 항암치료를 반드시 시행해야 함.
* Adjuvant Taxane+Herceptin 을 사용하기 위해서는 AC#4를 반드시 시행해야 함.
Herceptin SC
• 적응증 – 유방암에서 IV Herceptin과 동일한 적응증으로 허
가됨 • 용량: Fixed dose 600mg • 투여방법
– 3-5분간 허벅지에 피하주사 • 비용
– 130만원/Vial – 50kg이상의 경우 IV 보다 저렴
• 55kg: IV 2700만원 vs. SC 2300만원 • 45kg: IV 1850만원 vs. SC 2300만원
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
– 3개월 간격 cardiac function monitoring
• Node(-) Small Tumor (≤1cm) – Risk-Benefit 고려 (특히 poor risk feature (1cm size, high histologic grade, HR-,
young age등) 가진 경우
• 보험급여 기준 – 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+만 급여)
– 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)
Node (-)
Node (+)
≤ 0.5cm
0.6-1.0cm
> 1.0cm
No adjuvant CTx
Consider adjuvant CTx
Adjuvant CTx
Regimen ??
Adjuvant Chemotherapy Regimen
CMF ≒ AC
FAC FEC
TAC AC wP
TC
FEC T
AC T
ddAC T
CMF ≒ AC < TC TAC ≒ AC/FEC T < ddAC wP
• No single standard regimen in BC • Anthracycline-based Taxane
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 regimen은 현재 AC 용법을 사용해야만 보험 급여 적용이 됨
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
J Clin Oncol 2015 33:2353-2360.
TNBC subtype All Population
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 0011 • N=1491, 1997-1999 • Node (+) BC • T4, N3 제외
• GEICAM 98052 • N=1060, 1999-2003 • High-risk Node(-) BC • T >2cm, ER/PR-, HG
2 or 3, Age
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) 2주 간격 – DD EC: EC (90/600) 2주 간격 – DD Paclitaxel: Paclitaxel 175mg/m2 2주 간격 – Weekly Paclitaxel: Paclitaxel 80mg/m2
• DD regimen vs. Conventional Tx – CALGB 97411 – GIM Phase III2
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
Breast Cancer Res Treat (2015) 151:251–259
ER+ Patients (HR 0.93, 95% CI 0.82–1.05) P=0.25
All Patients
ER(-) Patients
Prophylactic G-CSF in DD AC
• Filgrastim – AC 항암치료 48시간 이후 시작하여 daily G-CSF
투여 (ANC가 nadir 지나서 회복될 때까지) – 단점: Real practice에서 적용하기 어려움, ANC
500이상인 경우 비보험
• Peg-filgrastim – AC 항암치료 24시간 이후에 한번 투여 – 단점: 90만원/V의 고가, 비보험 – Neulasta: original – Neulapeg, Dulastin: generic (60만원/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)
보험급여 기준
• T ≤ 0.5 cm: No adjuvant chemotherapy – pN1mi: Node (+)로 청구 가능
• 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 35세 미만 or HG 2-3 or TNBC): TAC#6
Dose dense regimen 사용은 급여 청구에 문제 없음
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 35세 미만 or HG 2-3 or TNBC): TAC#6
– Node (+): AC#4 T#4, TAC#6, TC#4 – Dose-dense regimen 사용 가능 (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 치료 중 EF 감소
– Baseline EF=55% – 6 Cycle후 EF=45%
• No CHF symptoms • Next Plan?
Herceptin 일시 중단하고 3주후 재평가 EF 회복하면 재투여 고려
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.
Adjuvant Chemotherapy �TNBC & HER2 SubtypeContentsHER2+ Breast CancerIndicationLearning PointsChoice of Chemotherapy RegimenCardiac Risk AssessmentB-31: Risk Factors for CHFCardiac Monitoring AlgorithmDuration of HerceptinHERA (Median f/u of 8 years)PHARE (Non-Inferior Study)BCIRG 006BCIRG-006 �(Anthracycline vs. Non-anthracycline)Small (