卵巢癌内科治疗现状与进展

癌（Ovarian

Cancer）发病与预后Incidence

MortalityCancerNumber

(%) ASR

(W)

Number (%)

ASR

(W)238719

3.6

6.1

151917

4.3

3.8Ovary癌分期StageIIIIIIIVDescriptionConfined

toovariesConfined

to

pelvisConfined

toabdomen/lymphnodesDistant

metastases比例20%5%58%17%5年生存率73%45%21%<

5%80706050403020100IIIIIIIV癌初诊时分期与预后时分期根据组织学类型分期透明细胞癌内膜样癌粘液性癌低级别浆液性癌高级别浆液性癌癌NOSI-II26.2%29.4%8.5%1.9%30%4.0%III-IV4.9%3.5%1.1%4.9%84.2%1.4%All10.4%10.3%3.6%3.5%70%2.1%指南

pletion

surgery/surgical

staging指南

化疗方案5-year

survivalrateThree

Randomized

Phase

III

Trials

with

3126

Patients75%100%0mmHR

(95%

CI)2.70 (2.37,

3.07)1.34 (1.21,

1.49)手术残留肿瘤（RT）对预后的影响Overall

Survival,

%1

mm

–

10

mm

vs0

mm>10

mm

vs1

mm

–

10

mmLog-rank:

P<.0011

mm

–

10

mm>10

mm0

12

24

36

48

60

72

84

96

108

120

132

144du

Bois

A,

et

al.

Cancer.

2009;115(6):1234-1244.50%25%0%du

Bois

A,

et

al.

Cancer.

2009;15(6):1234-1244.完全切除是肿瘤分期独立的预后因素InitialFIGO

Stage无残留病灶

有残留病灶HR(95%

CI)中位生存期,月+

60.3

months+

46.9

months+

30.0

monthsFIGO

IIB-IIIBFIGO

IIICFIGO

IV108.6

48.381.1

34.254.6

24.6HR

=

Hazard

ratio,

reference

class

for

HR

is

“指南EORTC

55955:

复发

早期治疗与延时治疗Ovarian

cancer

in

complete

remissionafter

-line

platinum-based

chemotherapyand

a

normalCA125CA125>2

x

upper

limit

of

normalRANDOMIZEDEarly

treatmentClinician

and

patient

informedDelayed

treatmentClinician

not

informed,

treatmentdelayed

until

clinically

indicatedREGISTERBlinded

CA125

measuredevery

3

monthsRustin

GJS,

et

al.

Lancet.

2010;376(9747):1155-1163.计划入组:1400目标:OS,TFS,

QoLEarly2652316Delayed264177116916956494233何时化疗？Rustin

G,

et

al.

ASCO

2009.1.Rustin

G,

et

al.

ASCO

2009.1.Early2652472111653122Delayed26423620353383119生存期–––––复发性

癌:

临床问题End

ofFrontlineTherapyRefractory

Resistansitive复发：铂敏感与铂耐药复发

癌:

无铂间期与生存期0-3Prog0-3

Non-PD3-12

Mos12-18

Mos18+

MosPFS,

days90176174275339OS,

days217375375657957Response,

%924355262DaysPercentagePujade-Lauraine

E,

et

al.

ASCO

2002.829.Months基于PFS1复发后生存期差异(到复发/进展0-6

月

vs

6-12

月 vs

12+

月)0-6

months

(558

patients/511

deaths)median

OS

8.1

months6-12

months

(641

/

567)median

OS

14.5

months12+

months

(889

/

528)median

OS

24.8

monthslogrank

P<.0001Andreas

du

Bois

20078

+

6

+

10month复发后治疗的选择Fullyplatinum-sensitive>12

MonthsCarboplatincombination

(PLD,Gemcitabine,or

Pa

axel)Platinum-resistant<6

MonthsNon-platinumsingle

agentPartiallyplatinum-sensitive6–12

MonthsOptions:PLD

+

CarboplatinPLD

+

TrabectedinPLD,

pegylated

liposomal

doxorubicin指南

+©

AdB癌复发患者化治疗时代-治疗路线图PFS-

奥拉

治疗

BRCA1/2

突变

*The

greatest

PFS

benefit

was

observedin

patients

with

a

BRCA1/2mutation

(BRCAm)

which

was

present

in

136

of

the

265

enrolled

pts.*Includes

patients

with

germline

and/or

somatic

mutations;

†patients

were

treated

until

disease

progressionLedermann

et

al.

Lancet

Oncol.

2014;15(8):852–861©

AdBsuperiorsuperiorsuperiorsuperior©

AdBPa axel

+CarboplatinGemcitabine

+CarboplatinPLD

+CarboplatinGemcitabine

+Carboplatin

+BevacizumabPa axel

+Carboplatin

+BevacizumabPlatinum

regimefollowed

byOlaparibPFS

TC

>

COS

TC

>

CPFS

CG

>

C

OS

?PFS

CC

>

TCOS

CC

=

TCPFS

CGB

>

CGOS

CGB

=

CGPFS

TCB

>

TCOS

TCB

=

TCPFS

Pt.+Ola

>

Pt.OS

n.s.Schedule:

d1q

3

wSchedule:

d1+8q

3

wSchedule:

d1q

4

wSchedule:

d1+8q

3

w→

d1

q3Schedule:

d1q

3

w+maintenanceSchedule:

d1q

3

w+maintenanceNeurotoxicityHematotoxicitySkin/mucosaHematotoxicityInfection

G3Joint

painof

Pt.

Regime+Fatigue

NauseaAlopecia

86%Alopecia

15%Alopecia

7%Hypertension

20%AlopeciaAnemiaNeurotoxicityQoL

identicalQoL

identicalQoL

identicalQoL

?QoL

identicalQoL

identical复发性

癌

铂类方案比较化疗联合贝伐单抗可增加有效率的症状控制耐药复发和敏感复发

癌©

AdB癌的分子分型LGSOCKRASBRAFMucinousKRASType

IIHGSOCTP53

/

RB

pathwayBRCA1/2ChromosomalinstabilityDISTINCT

DISEASES WITH

DIFFERENT

DRIVER

ALTERATIONSPatient

selection

based

on

robustpredictive

biomarkers=

key

to

success!!!!!LGSOC,

low

grade

serous

ovarian

carcinoma;

HGSOC,

high

grade

serous

ovarian

carcinomaDespierre

E,

et

al.

Int

J

Gynecol

Cancer.

2014;24:468-477.Type

IEndometrioidPTENPIK3CACTNNBClearCellPIK3CA

ARID癌常见5种类型High-GradeSerousMucinousLow-GradeSerousUsual

stage

atdiagnosisAdvancedClear

Cell

EndometrioidEarlyEarlyEarlyEarly

oradvancedPresumedtissue

oforigin/precursorlesionFallopiantube

or

tubalmetaplasiain

inclusionsof

OSEEndometriosis,adenofibromaEndometriosis,adenofibromaAdenoma-borderline-carcinomasequence;teratomaSerousborderlinetumorGenetic

riskBRCA

1/2???KRASSignificantmolecularabnormalitiesp53

and

pRbpathwayHNF-1βARID1ABRAF

orKRASProliferationHighLowH

CPTEN,β-Catenin,KRAS

MI,ARID1ALowIntermediaow80%15%?15%26-28%Response

toprimarychemotherapyPrognosisPoorIntermediateFavorableFavorableFavorable癌靶向治疗研究Angiogenesis

(no

validated

predictors)PARP

inhibitors

(high-grade

serous-

HRD)RAS-MEK

pathway

(low-grade

serous)ADC

(Folate

receptor,

NaPib2,

..)

(all

epithelial

ov

ca)EGFR

(erlotinib

negative

in

line)ErbB3

(eg,

pertuzumab,

...)

(Low

HER3

mRNA

expression)PI3K/AKT/mTOR

(PI3K:

Clear

cell)P53

(high-grade

serous)ing

cell

cycleImmuno-oncology,

eg,

anti-PD-1/PD-L1Variation

of

the

Sum

ofthe

Longest

Diameter,

%120100806040200-20-40-60-80CR,

complete

response;

PR,

partial

responseDisis

ML,

et

al.

J

Clin

Oncol.

2015;33(Suppl):.

5509.

Varga

A,

et

al.

J

Clin

Oncol.

2015;33(Suppl):5510.PR

(RECIST)PR

(irRC)Clear

cell-100A

tumor

size

decrease

≥30%has

been

observedin

11/75patients(14.7%)Phase

Ib

Trial

ofAvelumab(anti-PD-L1)KEYNOTE-028:Multicohort

Phase

IbTrial

of

Pembroli