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01. 항암제 임상시험 승인 현황02. General aspect of evaluation in
cancer
03. Endpoint in Cancer Clinical Trial
04. Response Criteria
05. Conclusions
CONTENTS
구분 종양 심혈관계 내분비계 중추신경계
소화기계 기타 효능군
계
2010 년 112 49 54 48 33 143 439
2011 년 112 69 41 47 29 205 503
2012 년 184 59 57 68 56 246 670
2013 년 157 80 51 46 40 233 607
식약처 신규 승인 임상시험
식약처 신규 승인 임상시험
2010
112건 /439건
25.5% 22.3% 27.5% 25.9%
2011
112건 /503건
2012
184건 /670건
2013
157건 /607건
1. Patient evaluation
평가기준- ECOG(Eastern Cooperative Oncology
Group) PS
- KPS (Karnofsky Performance Status)
항암치료의 원칙 ECOG 0, 1, 2 KPS≧70
환자의 일반적 건강상태 및 운동능력평가
2. Tumor evaluation by stag-ing병기 결정을 통해 치료 방침 결정 ,
환자 예후 예측 , 치료 결과분석 및 상호 정보교환
TNM 법
Tumor_ 원발종양의 크기 , 침윤 정도
Node_ 주변 림프절 침범 정도
Metastasis_ 다른 장기로 전이 여부
▷ TNM 법이 가장 많이 사용되나 ,
암의 종류에 따라 세부적인 차이 있으며독립적인 분류법에 따라 진행단계를 결정하는 경우도 있음
T
N
.M
3. Treatment response evalu-ation
After anti-cancer therapy
Response after variable agents
Selection of proper agent
Residual disease status
Toxicities
ETC
Time-to-Event outcomes1) Time between the day of registration/randomization to the date of a
event
2) Includes overall survival(OS), progression-free survival(PFS) or time-
to-progression(TTP), disease-free survival(DFS) or relapse-free sur-
vival(RFS), or other event-free survivals
Tumor shrinkage or stabilization 3) Response rate
4) Clinical benefit
Safety1) Toxicity (adverse events)
√ OS(Overall survival, 전체생존 ): 무작위배정 ~ 사망√ PFS(Progression free survival, 무진행생존 ): 무작위배정 ~ 종양진행 or
사망√ TTP(Time to tumor progression, 종양 진행까지의 시간 ): 무작위배정 ~
종양진행 ※ PFS 와 TTP 의 차이 ; TTP 는 종양진행 없는 사망은 제외
Time-to-Event outcomes1) Time between the day of registration/randomization to the date of a
event
2) Includes overall survival(OS), progression-free survival(PFS) or time-
to-progression(TTP), disease-free survival(DFS) or relapse-free sur-
vival(RFS), or other event-free survivals
Tumor shrinkage or stabilization 3) Response rate
4) Clinical benefit
Safety1) Toxicity (adverse events)
RECISTResponse Criteria
2000 년
WHOResponse Criteria
1979 년
Issue in WHO response criteria 1) Complexity - Needs bi-dimensional measurements - No minimum lesion size & number - Results may vary among research groups 2) New technologies 3) No longer regarded
WHO RECIST
Measurabil-ity
- Measurable, bi-dimen-sional(product of LD and greatest perpendicular diameter)
- Non-measurable/evalu-able
- Measurable,uni-dimen-sional (LD only, size with conventional techniques ≥ 20mm; spiral computed to-mography ≥ 10mm)
- Non-measurable: all other lesions, including small lesions. Evaluable is not recommended
Measurability of lesion at base-line
Measurable
Target le-sion
Non-target lesion
{ 병변의 반응 기준 }
Target le-sion
CRPRSDPD
Non-target lesion
Present=non-CR/non-PDAbsent=CRUnequivocal progression=PD
New lesion PresentAbsent
Baseline 에 선정된 Target
lesion 은 연구 종료시점까지 동일하게 유지
Objective responseMeasurable disease / Target le-
sionsWHO RECIST
Change in sum of products of LDs and greatest perpendicular diameters, no maximum No. of lesions specified
Change in sum of LDs, maxi-mum of 5 per organ up to 10 to-tal, more than one organ
CRComplete re-
sponse
Disappearance of all known dis-ease, confirmed at ≥ 4 week
Disappearance of all known dis-ease, confirmed at ≥ 4 week
PRPartial response
≥50% decrease from baseline, confirmed at ≥ 4 week
≥30% decrease from base-line, confirmed at ≥ 4 week
SDStable disease
Neither PR or PD criteria met Neither PR or PD criteria met
PDProgressive dis-
ease
≥25% increase of one or more lesions, or appearance of new lesions
≥20% increase over smallest sum observed, or appearance of new lesions
Objective responseMeasurable disease / Target le-
sionsWHO RECIST
Change in sum of products of LDs and greatest perpendicular diameters, no maximum No. of lesions specified
Change in sum of LDs, maxi-mum of 5 per organ up to 10 to-tal, more than one organ Max-imal 5 lesions (2 per organ)
CRComplete re-
sponse
Disappearance of all known dis-ease, confirmed at ≥ 4 week
Disappearance of all known disease, confirmed at ≥ 4 week(Required when response rate is primary endpoint)
PRPartial response
≥50% decrease from baseline, confirmed at ≥ 4 week
≥30% decrease from baseline, confirmed at ≥ 4 week(Required when response rate is primary endpoint)
SDStable disease
Neither PR or PD criteria met Neither PR or PD criteria met
PDProgressive dis-
ease
≥25% increase of one or more lesions, or appearance of new lesions
≥20% increase over smallest sum observed[+at least 5mm increase] or appearance of new lesions
{ Lymph nodes }Measuring short axis- ≥15mm: target node- <10mm: normal node
Objective responseNon-measurable disease / Non-target le-
sionsWHO RECIST
CRComplete re-
sponse
Disappearance of all known dis-ease, confirmed at ≥ 4 week
Disappearance of all non-tar-get lesions and normalization of tumor markers, confirmed at ≥ 4 week
PRPartial response
estimated decrease of ≥ 50% -
SDStable disease
Neither PR or PD criteria met
[ non-CR/non-PD ]Persistence of one or more non-target lesions and/or tumor markers above normal limits
PDProgressive dis-
ease
≥25% increase of one or more lesions, or appearance of new lesions
unequivocal progression of non-target lesions, or appear-ance of new lesions
Target lesion 반응 평가의 예
Baseline 1 차 평가 2 차 평가 3 차 평가 4 차 평가
Sum 200 150 135 150 180
Baseline 대비 100% 75% 67.5% 75% 90%
Nadir 대비 100% 111% 133%
Baseline
대비반응SD PR SD SD
Nadir 대비반응 SD PD
치료제 변경 시점
Overall Response
Time point response: A response assessment oc-
curs at
each protocol specified time point.
Target, Non-target, New lesion 의 모두 합한 반응 평가
Overall Response
Target Non-target New lesions Overall response
CR CR No CR
CR Non-CR/Non-PD No PR
PR Non-PD No PR
SD Non-PD No SD
PD Any Any PD
Any PD Any PD
Any Any Yes PD
BEST Overall Response
The best overall response is the best response recorded
from the
start of treatment until disease progression/
recurrence(taking as
reference for progressive disease the smallest measurements
recorded since the treatment started).
Best overall re-sponse
For CR and PR criteria must be met again 4 weeks after
initial documentation(this requirement ONLY for non-
randomized trials with primary endpoint of response)
When SD is believed to be best response, it must also
meet the protocol specified minimum time from base-
line. If the minimum time is not met when SD is other-
wise the best time point response, the patient’s best re-
sponse depends on the subsequent assessments.
Best overall re-sponse
For example,
1. A patient who has "SD" at first assessment, "PR" at second
assessment, and "PD" on last assessment has a best overall
response of "PR".
2. A patient who has “SD” at first assessment, “PD” at second
and does not meet minimum duration for SD, will have a best
response of “PD”. The same patient lost to follow-up after the
first SD assessment would be considered inevaluable.
반응 평가는 치료제의 변경 결정 및 효과 판정 근거가 되므로 중요
반응 평가를 위한 영상검사는 반드시 계획된 일정한 시기에 시행
Baseline 시 영상검사는 follow-up 때 동일한 방법으로 시행
RECIST 1.1 에도 남아 있는 문제점이 있으므로 개정을 통해 보완
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