![Page 1: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/1.jpg)
![Page 2: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/2.jpg)
01. 항암제 임상시험 승인 현황02. General aspect of evaluation in cancer03. Endpoint in Cancer Clinical Trial04. Response Criteria05. Conclusions
CONTENTS
![Page 3: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/3.jpg)
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
![Page 4: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/4.jpg)
식약처 신규 승인 임상시험
2010
112건 /439건
25.5% 22.3% 27.5% 25.9%
2011
112건 /503건
2012
184건 /670건
2013
157건 /607건
![Page 5: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/5.jpg)
1. Patient evaluation
2. Tumor evaluation by stag-ing
3. Treatment response evalu-ation
![Page 6: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/6.jpg)
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
![Page 7: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/7.jpg)
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
![Page 8: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/8.jpg)
3. Treatment response evalu-ation
After anti-cancer therapy
Response after variable agents
Selection of proper agent
Residual disease status
Toxicities
ETC
![Page 9: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/9.jpg)
Time-to-Event outcomes1) Time between the day of registration/randomization to the date of a
event2) 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 rate4) 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
![Page 10: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/10.jpg)
Time-to-Event outcomes1) Time between the day of registration/randomization to the date of a
event2) 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 rate4) Clinical benefit
Safety1) Toxicity (adverse events)
![Page 11: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/11.jpg)
RECISTResponse Criteria
2000 년WHO
Response Criteria1979 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
![Page 12: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/12.jpg)
WHO RECIST
Measurabil-ity
- Measurable, bidimen-sional(product of LD and greatest perpendicular diameter)
- Non-measurable/evalu-able
- Measurable, unidimen-sional (LD only, size with conventional techniques ≥ 20mm; spiral computed to-mograpy ≥ 10mm)
- Non-measurable: all other lesions, including small lesions. Evaluable is not recommended
Measurability of lesion at base-line
![Page 13: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/13.jpg)
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
![Page 14: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/14.jpg)
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-
sponseDisappearance 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
![Page 15: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/15.jpg)
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-
sponseDisappearance 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
![Page 16: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/16.jpg)
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 target le-sions and normalization of tu-mor 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
![Page 17: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/17.jpg)
Target lesion 반응 평가의 예Baseline 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%
Baseline대비반응 SD PR SD SD
Nadir 대비반응 SD PD
치료제 변경 시점
![Page 18: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/18.jpg)
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
![Page 19: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/19.jpg)
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
![Page 20: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/20.jpg)
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).
![Page 21: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/21.jpg)
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.
![Page 22: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/22.jpg)
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.
![Page 23: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/23.jpg)
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
![Page 24: 01. 항암제 임상시험 승인 현황 02. General aspect of evaluation in cancer](https://reader036.vdocuments.mx/reader036/viewer/2022081507/56816249550346895dd28b46/html5/thumbnails/24.jpg)