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La sequenza nel trattamento del carcinoma ovarico sieroso ad alto grado nel 2019

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(1)

Caso clinico

La sequenza nel trattamento del carcinoma ovarico sieroso ad alto

grado nel 2019

Mara Mantiero

Università degli Studi di Padova Istituto Oncologico Veneto IRCCS

mara.mantiero@iov.veneto.it

(2)

Medical History

F.L. , 43 years old

 Premenopausal status, nulliparous

 Never smoker, no comorbidities

 No family history for breast/ovarian cancer

(3)

November 2012

Acute Dyspnea and tachycardia:

 Cardiologic evaluation: negative

 Thoracic X-ray: right pleural effusion

 Thoracentesis & Cytological evaluation pleural fluid:

positive for MTC, WT1+ serous carcinoma

 c/a CT scan: limited right pleural effusion with pleural thickening […] solid masses in both ovaries (diam max 46mm) with pelvic free fluid […]

 Ca125 = 144 kU/L (CEA, CA19.9, CA15.3 neg)

(4)

Diagnosis & Surgery

 05.12.2012: PRIMARY DEBULKING SURGERY

Hysterectomy + bilateral adnexectomy, appendectomy, omentectomy, pelvic and para-aortic lymphadenectomy, peritoneal biopsies (RT=0)

Final Histological Evaluation:

High grade serous carcinoma of both ovaries, FIGO IVa (pleura)

 Germline BRCA test: wild type

(5)

Treatment

maintenance

Jan 2013

CBDCA AUC6 + Paclitaxel 175 mg/mq + Bevacizumab 15 mg/kg

q21 x 6

Bevacizumab 15 mg/kg q21

1st line

CT scan: NED CA125= neg

ESMO OC Guidelines

PFI 9 = PPS

Feb 2014

CT scan:

Right pleural effusion

Surgery:

Right Pleurectomy

Follow-up

May 2013

2nd line

PLD 30 mg/mq + Trabectedine 1,1mg/mq

q21 x 5

Hematologic Toxicity

CT scan: NED CA125= neg

Aug 2014

(6)

Treatment

Jul 2016

CT scan: CR CA125= neg

INCLUSION CRITERIA - Niraparib

 Serous or endometrioid OC

 High Grade

 At least 2 lines Platinum-based therapy

 Last PFI > 6 months

 CR or PR to last Platinum-based therapy

Jan 2016

CT scan:

Peritoneal carcinomatosis

+ ascites

CA125= 173 kU/L

3rd line

CBDCA AUC5 + Gemcitabine

1000mg/mq d1,8 q21 x 2

CBDCA AUC5 q21 x 4

Follow-up Follow-up

May 2017

CT scan:

Pararectal and parasplenic

nodes

CA125= 160 kU/L

PFI = 10 CBDCA AUC2 + Paclitaxel 60 mg/mq

q7 x 19

Sep 2017

11.09.2017 CT scan: PR CA125= 40 kU/L

4th line

(7)

Treatment

NIRAPARIB

C1 300 mg/die PLTpenia G3 C2 200 mg/die Anemia G3 C3 100 mg/die

Sep 2017

maintenance

(8)

Niraparib

Berek JS et al. Annals of Oncology 2018

• For patients weighing less than 58kg a starting dose of 200mg may be considered

(9)

Treatment

RT 24Gy/3f

maintenance

NIRAPARIB 100 mg/die

ongoing

Feb 2019

CT scan:

Increased single pararectal node

(29 vs 12mm)

maintenance

Sep 2017

NIRAPARIB

C1 300 mg/die PLTpenia G3 C2 200 mg/die Anemia G3 C3 100 mg/die

(10)

PARPi & RT

(11)

Platinum sensitivity

BRCA status

Clinical

Trial Surgery &

RT

…and then?

(12)

Clinical Trial:

2

options

(13)

Clinical Trial

 Ovarian cancer

 Recruiting

(14)

• Watch&wait was the prior standard of care for recurrent ovarian cancer after CT.

NOW:

 maintenance therapy with PARPi changed clinical practice in ovarian cancer

 pro-active management of side-effects of PARPi maintains quality of life

• Consider local treatment (surgery or RT) for single or oligometastatic relapse, also during PARPi.

• Remember Clinical trials!

• Open questions:

- Bevacizumab or PARPi, which sequence? (…PRIMA trial?) - Long-term toxicity of PARPi?

Conclusions

(15)

BRCA test

BRCAmut may be present in 15-44% of individuals with no family history of ovarian/breast cancer

• Il test BRCA è consigliato a tutte le pazienti con carcinoma ovarico non- mucinoso e non-borderline, carcinoma delle tube di Falloppio o carcinoma peritoneale primitivo.

Hoogerbrugge N, Eur J Hum Genet, 2016

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