Il punto di vista dell’esperto

Giovanni Scambia

Polo Scienze della Salute della Donna e del Bambino

Il parere dell’esperto

• Ovarian cancer in the Era of Personalized Medicine

• Tailored Surgery for Ovarian Cancer

• Cervical cancer

Menagin Ovarian Cancer in the Era of

Personalized Oncology

OC is not one disease

Outcome depends on histotype

PARP inhibitors in ovarian cancer:

current status and future promise

OLAPARIB (Lynparza ®)

FDA approved: mantainance therapy in platinum sensitive relapse high grade ovarian cancer + Deleterious BRCA mutation associated with advanced ovarian cancer EMA approved: mantainance therapy in BRCA + platinum sensitive relapse high grade ovarian cancer

NIRAPARIB (Zejula®)

FDA + EMA approved:

mantainance therapy in platinum sensitive relapse high grade ovarian cancer

RUCAPARIB (Rubraca®) FDA approved:

Deleterious BRCA

mutation associated with advanced ovarian cancer

VELIPARIB

TALAZOPARIB

Quality of Life?

NACT RATIONALE in ONCOLOGY

NACT in ADVANCED OVARIAN CANCER

 Clinical evidences supporting NACT

 Potential risks of NACT

 Catholic University management

NACT PERSPECTIVES

 “Tailored” treatment

ITEMS

Neoadjuvant ChemoTherapy: PRINCIPLES

New strategy to increase resectability (“to downstage” the patient) on head and neck cancer

1982

To shrink the tumor in patients who were not candidates for primary surgery, and to allow

organ preservation 

 reduction of mortality rate

1990s-2010s

PROSTATE CANCER

BREAST CANCER

COLO-RECTAL CANCER

LUNG CANCER

Cancer statistics, 2017

A.Fagotti et al. (EJC - 2016) RESIDUAL DISEASE

EARLY (<30days) COMPLICATIONS LATE 1-6 months from surgery) COMPLICATIONS

NACT vs PDS: RCTs

 Single institution Phase III Randomised clinical trial

 110 eligible women, 55 assigned to arm A (PDS) and 55 to arm B (NACT+IDS)

 AEOC supposed resectable women with PI > 8 or < 12 (considered as HTL) were included

 2 arms: A) PDS followed by systemic adjuvant chemotherapy ; B) NACT followed by IDS

 2 Co-primary outcomes: post-operative complications

& PFS

- NACT /IDS is better than PDS in patients with HTL (PI >8 and

< 12) in abdomen, as assessed by s-LPS, in terms of

perioperative morbidity

- No differences in QoL measurements at the end of

treatment between the 2 arms.

PATIENTS’ SELECTION

SURGICAL EFFORT

High and uniform SCS

Procedures endowed with high SCS (score =2-3) were required in 100% versus 48.1%, in PDSarm versus

NACT/IDS arm , respectively (p = 0.0001)

Gynecologic Oncology - 2015

Level of evidence: IIB

MIS approaches may be useful when evaluating

whether maximum cytoreduction can be achieved in

newly diagnosed and recurrent OC 109,122,123,135,136

Variation in NACT at high volume hospitals

Gynecologic Oncology - 2017

 11.574 pts with FIGO stage IIIC – IV of OC.

 78.4% received PDS, while 21.6%

treated with NACT/IDS.

 All woman treated at 55 high volume hospitals (>20 cases/year), classified in:

• Low utilization of NACT (14)

• Average utilization of NACT (31)

• High utilization of NACT (10)

Utilization of NACT to treat stage IIIC and IV OC varies widely among high volume hospitals.

Receipt of care at a hospital with an average or high NACT use rate was associated with a decreased rate of death compared to care at a low utilization hospitals.

It is plausible that low utilization of NACT is associated

with increased suboptimal primary cytoreductive

surgery rates and increased major postoperative

complications with adjuvant treatment delays, both

leading to decresed survival. Further research is needed.

 NACT+IDS pts showed more frequently

carcinomatosis, and platinum-resistant disease at recurrence compared with PDS

 Patients treated with NACT+IDS showed a shorter Post-Relapse survival compared with PDS (3-yrs PRS, PDS=58% vs NACT-IDS=18% )

NACT-IDS negatively influences the pattern and timing of recurrence, probably favoring the selection

of chemoresistant clones

Potential risks of NACT

Annals of Surgical Oncology, 2013

Potential risks of NACT

2015

Incorporation of Bevacizumab into upfront regimens prolongs PFI in AOC patients, but is associated with a more aggressive behaviour of recurrent disease:

1) Wider presentation of relapse ( p 0.035)

2) Lower percentage of patients suitable for SCS ( p 0.016)

3) Shorter TTP to second line chemotherapy in women with platinum-sensitive disease (p-value ( p-value 0.041)

2016

Gynecologic Oncology

CATHOLIC UNIVERSITY MANAGEMENT OF AOC

·OVARIAN CANCER SURGERY - GUIDELINES·

1

OV ARI AN CANCER SURGERY GUI DEL I NES

- Complete r epor t -

·OVARIAN CANCER SURGERY - GUIDELINES· 1

OVARIAN CANCER SURGERY GUIDELINES

- ASSESSMENT FORM -

SURNAME:

FIRST NAME(S):

COUNTRY:

PLEASE PROVIDE YOUR DISCIPLINE(S) OR SPECIALITY(IES):

·OVARIAN CANCER SURGERY - GUIDELINES·

3

ALGORITHM FOR EPITHELIAL OVARIAN CANCER SURGERY (2)

Strongly disagree Indecision Strongly agree

ò ò ò

1 2 3 4 5 6 7 8 9

Do you feel that this algorithm is clinically relevant?

Do you feel that this algorithm is usable in your practice?

·

Open commentary - Elements supporting your position (e.g. clinical arguments, bibliographic data, etc.)

·

MANDATORY if at least one score is < 7 (optional in other situations)

S-LPS

Vizzielli score

S-LPS

Vizzielli score

31

MINIMALLY INVASIVE SURGERY after NACT

Am J Obstet Gynecol 2016

Minimally Invasive-IDS in patients with clinically complete response to NACT seems to be feasible

and safe in terms of perioperative outcomes, psycho-oncological impact, and survival rate.

A high level of satisfaction was informally recorded for our patients, in line with the fact that a scarless surgery may help to avoid an unnecessary mark of a difficult history,

and reduce postoperative pain.

 Multicentric phase II Clinical Trial

 Of 184 advanced EOC patients

considered eligible for IDS, finally

30 woman received the planned

treatment of MI-IDS.



Minimally invasive approach could represent an advantageous

alternative surgical way to perform interval debulking surgery in this specific subset of patients.



MIS is superior to standard laparotomy in terms of EBL, discharge time and TTC.



MI approach determines a higher percentage of women with positive well-being compared to pts treated with the conventional approach.

Women treated with

MI-IDS showed a 6 months longer

PFS compared to Controls

MINIMALLY INVASIVE SURGERY after NACT

Gyn Oncology - 2016

• Retrospective cohort study

• 3.071 pts with AOC, who underwent NACT and IDS

• 47.5% LPS vs 52.5% LPT

 No difference in survival between women who underwent laparoscopic IDS and those underwent laparotomy.

 Short postoperative hospitalization after laparoscopic surgery and no difference in risk of unplanned readmission or perioperative death.

 In well-selected pts, such as those who have a complete response to NACT, laparoscopic IDS may be a safe and effective alternative to laparotomy.

• Relatively short FU (3 ys)

• Lack of random allocation

• Inability to verify registry data

• Retrospective case-control study

• 30 AEOC pts treated with MI- IDS; 65 submitted to LPT-IDS

• Small sample size

• Short duration of median FU

 AOC pts with BRCAmut are highly responsive to P-based

chemotherapy, with also prolonged PFS after NACT , compared with BRCA naïve.

Gorodnova TV, et al. Cancer Letter, 2015;

Mahdi H, et al. Gynecol Oncol 2015

MOLECULAR CHARACTERIZATION FOR NACT

PDS

NACT

Submitted

Progression-free survival (%)

PDS

NACT

p=0.05

p=ns BRCAwt

PDS NACT Median PFS

26 months 18 months

BRCAmut

PDS NACT Median PFS

28 months

24 months

Neoadjuvant ChemoTherapy: PRINCIPLES

New strategy to increase resectability (“to downstage” the patient) on head and neck cancer

1982

To shrink the tumor in patients who were not candidates for primary surgery, and to allow

organ preservation 

 reduction of mortality rate

1990s-2010s

PROSTATE CANCER

BREAST CANCER

COLO-RECTAL CANCER

LUNG CANCER

Cancer statistics, 2017

To test the activity of a therapeutic

approach or the potential importance of biological factors in

determining disease outcome 2017

Achiving a complete pathologic response seems to correlate to the best prognosis ever achieved

2010s

J Clin Oncol 30:1796-1804, 2012

Ann Surg Oncol (2012 ) BREAST CANCER

COLO-RECTAL CANCER LUNG CANCER

AJOG (2014)

OS PFS

PATHOLOGICAL RESPONSE TO NACT

• cPR : cases with no residual neoplastic cells in all the surgical specimens, including the adnexa

• microPR : microscopic foci (maximum diameter ≤ 3 mm)

• macroPR : persistent macroscopic site of disease after NACT

• cPR is an uncommon event in AOC patients receiving NACT and is associated with a longer PFS and OS compared with women showing no cPR

• cPR, rather than only an

estimation of disease extension after NACT, clearly emerges as a marker of extreme sensitivity to platinum-based

chemotherapy.

Neoadjuvant ChemoTherapy: PERSPECTIVES

Neoadjuvant ChemoTherapy: PERSPECTIVES

BRCA1=27%

Olaparib with weekly JM8 and TAX as NACT in BRCA mut advanced HGSOC women: a PHASE II multicentric study

PRIMARY AIM: Pathological complete response after 3 cycles of NACT including OLAPARIB and weekly JM8-TAX in BRCAmut advanced HGSOC

SECONDARY AIMS: Complete cytoreduction rate at IDS, response rate (RECIST

criteria), surgical assessment of response with a laparoscopic standardized score

(Fagotti score), toxicity Profile, PFS,OS.

Suspicious AEOC : GYO + imaging + S-LPS

TISSUE ACQUISITION

Histology & molecular analysis

TUMOUR LOAD

& peri-op risk

LTL/ITL<8

Low peri-op risk PDS

HTL 8-12

High peri-op risk

CHEMORESISTANT (LGSOC; mucinous;

BRCA wt)

CHEMOSENSITIVE

(High grade; BRCA mut;

TGF-beta pathway)

Discuss with the pt PDS or NACT

Offer exp. treatment NACT with target treatment

Unresectable

NACT

75%

<5%

20-25%

Catholic University Integrated Algorithm for

Personalized Treatment in HGSOC

CONCLUSIONS...

We are moving from generalized guidelines, where PDS is still against NACT, to tailored approaches where PDS and NACT are both first-line available treatments that we need to

carefully choose for EACH patient

DON’T MAKE IT LOOK GOOD ON YOU BUT

MAKE IT GOOD FOR YOU

KEY POINTS

•

• CARATTERIZZAZIONE MOLECOLARE

• CHIRURGIA TRATTAMENTO MEDICO

•

where are

we going ?

Unanswered questions

 Early stage and fertility sparing tratments

 Sentinel node

 Adjuvant treatment

 Local Adavenced disease (Prognostic groups)

 Neoadjuvant chemotherapy

 Metastatic cervical cancer

 Target Therapy

What is the appropriate endpoint?

Should we do phase II or phase III studies?

Proposed primary endpoints included overall survival (OS), progression free survival (PFS), and response rates (ORR). Secondary endpoints included PFS, quality of life (QOL), patient reported outcomes (PRO), and safety

News in cervical cancer ?

Int J Gynecol Cancer. 2016 Jan;26(1):199-207

Feb-1999: NCI issues clinical announcement on cervical cancer

1.reduction in risk of death (HR 0.69, 95% CI 0.61-0.77)

2.reduction in risk of local recurrence (OR 0.59, 95% CI 0.50-0.69) 3.trend in reduction of distant metastasis (OR 0.81, 95% CI 0.65-1.01)

I.V. CISPLATIN CHEMOTHERAPY Cisplatin 40mg/m2 (Max dose 70mg)

IV q wk during RT (6wks) EXTERNAL BEAM

pelvic

radiation(40 to 60 Gy)

BRACHYTHERAPY (8,000 to 8,500 cGy

to Point A)

CTRT: CONSIDERED THE WORLD

STANDARD TREATMENT for LACC

OTHER OPTIONS

• Chemo/radiation

• Chemo/radiation followed by surgery

• Neoadjuvant chemotherapy

• followed by surgery

• followed by chemo/radiation

• Trial closed for poor accrual

• No difference OS between

surgery vs no surgery after CTRT

• This study failed to

demonstrate that RH after

EBRT-CT is superior to

standard BCT

Accrual: 103 pts

Eligibility

Cervix carcinoma stage IB2-IVA

Age<80y

Adequate bone marrow function

Adequate renal function Normal liver function

T

Clinical Response

-CR 36 pt(34.9%) -PR 63 pt(61.2%) -SD 2 pt(1.9%) -PD 2 pt(1.9%)

RT

39.6 GY(PELVIC LYMPH NODE DRAINAGE, BULKY TUMOR,PARAMETRIA) + 10.8 GY(PRIMARY

TUMOR,PARAMETRIA)

CT

CISPLATIN 20 MG/M2 P1Q25+CAPECITABINE 1300 MG/M2 DAILY

DFS 73%

OS 86.1%

TOXICITY

-Leukopenia 19.4% G1 19.4% G2 -Gastrointestinal 32% G1

9.7% G2 -Genitourinary 11.6% G1 2.9% G2

RELAPSE 25 pt(24.3%) DEATH 10 pt(9.7%)

Ferrandina et al. Int J Radiat Oncol Biol Phys 2014 RADICAL HYSYTER

ECTOMY

3 years

OTHER OPTIONS

• Chemo/radiation

• Chemo/radiation followed by surgery

• Neoadjuvant chemotherapy

• followed by surgery

• followed by chemo/radiation

NACT: AIMS

 DEBULKING EFFECT AND TUMOR SIZE REDUCTION

 IMPROVING SURGICAL OUTCOMES

 BETTER ACTIVITY AGAINST MICROMETASTASIS

 PERMIT CONSERVATIVE SURGERY

 LESS TOXICITY

 EASIER MANAGEMENT OF SALVAGE THERAPY

OTHER OPTIONS

• Chemo/radiation

• Chemo/radiation followed by surgery

• Chemo/radiation-chemotherapy

• Neoadjuvant chemotherapy

• followed by surgery

• followed by chemo/radiation

IB2 to III stages

Tierney et al. Eur J Cancer 2003

• 5 randomized trials

• 872 pts (97% of total)

• Stage:

 IB 35%

 II 38%

 III 26%

NACT & RS vs RT

EORTC 55994 (started 1999 !!!)

INCLUSION CRITERIA

•FIGO IB2, IIA, IIB

•PS 0-2

•Age 18-75

•Squamous

•Adenocarcinoma

•Adenosquamous

STRATIFICATION

• FIGO

• Institution

• Age 18-50 vs 50-75

• Histology:

 Squamous vs

 Adenocarcinoma vs

 Adenosquamous

ENDPOINTS

• Primary: OS

• Secondary:

 PFS

 Toxicity

 QoL

R A N D O M

Cisplatin based chemotherapy:

Min. total dose of 225 mg/mq

25 mg/mq per week

Final dose no later than 8°week

Radical hysterectomy

Chemo-radiotherapy

• CDDP 40 mg/mq (6 week) + EBRT 45-50 Gy

OTHER OPTIONS

• Chemo/radiation

• Chemo/radiation followed by surgery

• Chemo/radiation-chemotherapy

• Neoadjuvant chemotherapy

• followed by surgery

• followed by chemo/radiation

TREATMENTS IN LACC

• Chemo/radiation

• Chemo/radiation followed by surgery

• Neoadjuvant chemotherapy followed by chemo/radiation

• Neoadjuvant chemotherapy followed by surgery

CHEMOTHERAPY IS MANDATORY!

But how can we choose???

KEY QUESTIONS

Carboplatin or cisplatin?

WHICH Platinum doublet?

Which role for TARGET THERAPY in CC?

+2,2 m

+3,5 m

CECILIA (MO29594): trial design

• AUC, area under the concentration curve; q3w, every 3 weeks

*Minimum of 6 cycles, unless toxicity necessitates discontinuation of one or both chemotherapy agents, in which case non-implicated drug(s) and Bevacizumab can be continued alone

Metastatic, recurrent or persistent cervical

cancer patients not amenable to curative

treatment with surgery and/or radiation therapy

n=150

Until disease progression, unacceptable

toxicity or withdrawal of consent Paclitaxel 175mg/m

²

q3w*

Carboplatin AUC5 q3w*

Bevacizumab 15mg/kg q3w

A MULTICENTRE OPEN-LABEL SINGLE-ARM PHASE II STUDY EVALUATING THE SAFETY AND EFFICACY OF Bevacizumab IN COMBINATION WITH CARBOPLATIN AND PACLITAXEL IN PATIENTS WITH METASTATIC, RECURRENT OR PERSISTENT CERVICAL CANCER

MO29594– Adapted from

https://clinicaltrials.gov/ct2/show/NCT02467907?term=bevacizumab+cervical&rank=5

Randomize

Carboplatin AUC5 + Paclitaxel 175mg/m

²

+ Nintenanib 200 mg Bid

Weeks 1-6

Nintenanib until progression

Primary End-point: PFS

Secondary End-point: OS, Toxicity, Patient Health status

Ongoing Trial: Phase II, randomized, double bind and placebo controlled trial

Carboplatin AUC5 + Paclitaxel 175mg/m

²

+

Placebo Bid

Weeks 1-6

Placebo until progression

Figo IVB/recurent disease

NINTENANIB

Advanced cervical carcinoma (FIGO stage IIB-IIIB or IB- IIA with pelvic node

metastasis and/or tumour size ≥ 5 cm

n=57

RT/BRT 45 Gy (over

5 ws in 25 once daily fractions)

Bevacizumab 10 mg/kg Iv q2 weeks (days 1, 15 and

29, total 3 doses) during chemoradiation, before cisplatin and on the same

day as cisplatin

Phase II, single arm trial

Primary endpoints: treatment-related serious adverse events rates and adverse events rates within the first 90 days

Secondary endpoints: treatment-related serious adverse events rates and adverse events rates at any time, DFS, OS, angiogenic markers

Schefter et al IJR Oncol Biol Phys. 2012,2014

The Catholic University GYO Network

Dpt. Ob/GYN

Gemelli Hospital, Rome

Dpt. Oncology

Centre for Research, Campobasso

Campobasso Chieti

Acquaviva delle Fonti Palermo

Novara Abano

Terme

Gyn Onc Unit University of Palermo Gyn Onc Unit

University of Chieti

Gyn Onc Unit

University of Piemonte Orientale

Gyn Onc Unit Miulli Hospital, Acquaviva delle Fonti

SITE Essen criteria Leuven criteria Abdominal

metastases

Multiple parenchymatous liver metastases

Infiltration of large parts of the pancreas (not only tail) and/or the duodenum

Infiltration of the porta hepatis or truncus coeliacus

Deep infiltration of the radix mesenterii

Diffuse and confluent carcinomatosis of the stomach and/or small bowel

Involvement of the SMA

Intraephatic metastases

Infiltration of the duodenum and/or pancreas and/or the large vessels of the porta hepatis or truncus coeliacus

Extra-abdominal metastases

Not completely resectable metastases All, excluding: resectable

inguinal lymph nodes, solitary retrocrual or paracardial nodes, Pleural fluid cytologically

malignant cells without presence of pleural tumors

Pts characteristics Poor PS-ECOG

Vergote I and Du Bois A, 2012

Criteria for suboptimal debulking surgery in AOC

Borley J, BJOG, 2014

Predictive performances of CT scan in AEOC

findings confirm previously reported results (Bristow et al, 2000;

Chi et al, 2000; Cooper et al, 2002; Saygili et al, 2002; Memarzadeh et al, 2003), and definitively recognise the extent of the impact played by ECOG-PS in the preoperative prediction of ovarian cancer primary resectability (Aletti et al, 2007). The models based on diagnostic performance and on results from multivariate

analysis showed the same accuracy in predicting the chance of optimal cytoreduction, although they included slightly different CT-based features; in particular, involvement of bowel mesentery, omentum, liver, and diaphragm were shown to fulfil all the required criteria (Bristow et al, 2000) in Approach A, whereas in multivariate analysis the involvement of peritoneum and suprar- enal aortic lymph nodes, besides bowel/mesentery and diaphragm disease, were independently associated with suboptimal cyto- reduction. The divergence between the two approaches remains difficult to explain, although the strict and, to a certain extent, unpredictable associations among the variables might more likely have an impact on multivariate analysis. In any case, our findings support the relevance of the assessment of the status of bowel mesentery and diaphragm involvement, recognised among the most important features determining the feasibility of ovarian T able 4 Prediction of optimal cytoreduction: univariate and multivariate analysis by logistic regression of CT-based and clinically assessed parameters to use for modeling (Approach B)

U nivar iat e Mult ivar iat e

v² P-value v² P-value Point^a

Radiographic

Peritoneal thickening, peritoneal implants 4 2 cm 16.34 0.0001 3.45 0.063 1

Bowel mesentery involvement 17.50 0.0001 5.35 0.0207 1

Omental extension (spleen, stomach, lesser sac) 11.13 0.0008 2.52 0.11 0

Pelvic sidewall involvement and/or hydroureter 2.28 0.13 — — 0

Suprarenal aortic lymph nodes 4 1 cm 4.21 0.040 4.36 0.036 1

Infrarenal aortic lymph nodes 4 2 cm 8.15 0.0043 — — 0

Superficial liver metastases 4 2 cm and/or intraparenchimal liver metastases any size 8.58 0.0034 — — 0

Large volume ascites (4 500 ml) 8.15 0.0043 — — 0

Diaphragmatic disease (widespread infiltrating carcinomasis, or confluent nodules) 25.35 0.0001 7.13 0.0076 1 Clinical

Age, years (p 65 vs 4 65) 2.51 0.08 — — 0

Ca125 levels (p 500 vs 4 500 IU ml ¹) 2.98 0.11 — — 0

ECOG-PS (0,1 vs 2) 19.71 0.0001 14.22 0.0002 1

aOnly variable achieving a P–value o 0.10 were assigned a point value. Statistically significant values have been indicated as bold values.

0 10 20 30 40 50 60

0 1 2 3 4

Counts

PI

5

Model 3 Model 4

0 0.2 0.4 0.6 0.8 1.0

0 0.2 0.4 0.6 0.8 1.0

Sensitivity

1-Specificity

Model 3 Model 4

Figur e 2 Distribution of predictive index values (A ) and ROC curves (B) in Model 3 and Model 4.

T able 5 Pre-test probability, likelihood ratio, and post-test probability for different predictive models of primary optimal cytoreduction in ovarian cancer

T est Cut off

Pr e-t est pr obabilit y

Posit ive likelihood r at io

Post -t est pr obabilit y

Model 2 5 55.8 9.86 92.6

Model 4 3 55.8 10.25 92.8

T able 6 Performance of Approach A (Model 2) in defining the rate of patients unnecessarily explored or inappropriately unexplored

Model 2

PIV

U nnecessar i ly explor ed (1 N PV) (%)

Inappr opr iat ely unexplor ed (1 PPV) (%)

0 17.9 28.8

1 25.0 27.6

2 33.3 19.4

3 39.0 18.2

4 48.1 16.3

5 50.0 7.4

6 53.6 5.0

7 54.3 0

CT scan and cyt or educt ion in ovar ian cancer G Ferrandina et al 1070

British Journal of Cancer (2009) 101(7), 1066–1073 & 2009 Cancer Research UK

C lin ic a l S tu d ie s

Ferrandina G, BJC, 2009

1-Specificity

Sensitivity

0.0 0.2 0.4 0.6 0.8 1.0

0.00.20.40.60.81.0

AUC= 0.758

Suidan RS, Gyn Onc, 2014 AUC3= 0.78

AUC4= 0.82

Rutten IJGC, IJGC, 2016 Ferrandina (model B) AUC

0.82

Reader 1 0.55

Reader 2 0.60

Reader 3 0.59

NACT RATIONALE in ONCOLOGY

NACT in ADVANCED OVARIAN CANCER

 Clinical evidences supporting NACT

 Potential risks of NACT

 Catholic University management

NACT PERSPECTIVES

 “Tailored” treatment

ITEMS

CHORUS TRIAL

Kehoe et al, Lancet 2015

NACT vs PDS: RCTs

• Selection bias in recruitment of patiens believed to be inoperable with high tumor load

(Fotopolou at al. JCO-2017)

PFS = 12m (IDS) vs 10,7 m (PDS)

mOS= 24,6m (IDS) vs 22,6 m (PDS)

EORTC TRIAL

Vergote et al, NEJM, 2010

mOS = 30 m (IDS) vs 29 m (PDS)

Low survival rates due to:

• 1) patients’

selection;

• 2) surgery was substandard compared with that in other trials;

(S.Chi at al. “is the easy way ever the better way?”JCO- 2011)

• Multicentric RCT (87 hospitals in the UK and New Zealand)

• 550 women with FIGO stage III or IV of OC randomized

• 276 PDS vs 274 NACT/IDS

• Median FU: 52m

• Multicentric RCT (59 institutions)

• 718 pts enrolled, 670 women with biopsy- proven FIGO stage IIIC or IV OC randomized

• 336 PDS vs 334 NACT/IDS

• Median FU: 55m

Although these trials show non inferior results of NACT with lower morbidity, they have not neglegible bias in terms of

PATIENTS’ SELECTION and SURGICAL

EFFORT

NACT RATIONALE in ONCOLOGY

NACT in ADVANCED OVARIAN CANCER

 Clinical evidences supporting NACT

 Potential risks of NACT

 Catholic University management

NACT PERSPECTIVES

 “Tailored” treatment

ITEMS