La terapia di seconda linea: TKI o immunoterapia?

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LA TERAPIA DI II LINEA:

TKI o IMMUNOTERAPIA ?

Michele De Tursi

Dipartimento di Scienze Mediche, orali e biotecnologiche Cattedra di Oncologia Medica

Università G. D’Annunzio Chieti

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7

10

2

5

0 2 4 6 8 10 12

Kidney Breast Prostate Lung

22,9 27,9

38,9

4.0

0 5 10 15 20 25 30 35 40 45

Lung Prostate

Breast Kidney

A disproportionate number of approved targeted therapies for mRCC vs. number of patients

Incidence per 100,000 population 5

Number of approved targeted therapies for metastaticdisease

Cancer type

Kidney¹ Breast² Prostate³ Lung⁴

1. Escudier B, et al. Ann Oncol 2012;23(Suppl 7):vii65-vii71.

2. Cardoso F, et al. Ann Oncol 2012;23(Suppl 7):vii11-vii19.

3. Heidenreich A, et al. EAU Prostate Cancer Guidelines, 2014.

4. Peters S, et al. Ann Oncol 2012;23(Suppl 7):vii56-vii64.

5. GLOBOCAN 2008. Available at: http://globocan.iarc.fr/

Number of targeted therapies Incidence

5

Elaborazione grafica di dati da testo

I nuovi farmaci Target

II linea RCC

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Choice of 2^nd line therapies: PFS

Rini et al. Lancet 2011. Hutson et al. JCO 2014. Motzer et al. Cancer 2010. Motzer et al. (2015). NEJM, 150925150201006–11. Choueiri et al. (2016). The Lancet Oncology, 17(7), 917–927. Motzer et al. (2015) Lancet Oncology, 16(15), 1473–1482.

AXITINIB: 4,8 EVEROLIMUS: 4,9

LENVATINIB: 4,8 TEMSIROLIMUS: 4,3

NIVOLUMAB: 4,6

CABOZANTINIB: 7,4

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Strategie terapeutiche a confronto in II linea

Nivo ?

Cabo ? Axi ?

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AXITINIB

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AXITINIB

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Stato dell’arte AXITINIB

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AXITINIB

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CheckMate 025:

A randomized, open-label, phase III study of nivolumab versus everolimus in

advanced renal cell carcinoma

Padmanee Sharma, Bernard Escudier, David F. McDermott, Saby George, Hans J. Hammers, Sandhya Srinivas, Scott S. Tykodi, Jeffrey A. Sosman, Giuseppe Procopio, Elizabeth R. Plimack, Daniel Castellano, Howard Gurney, Frede Donskov, Petri Bono, John Wagstaff, Thomas C. Gauler, Takeshi Ueda,

Li-An Xu, Ian M. Waxman, Robert J. Motzer, on behalf of the CheckMate 025 investigators

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Disease assessments

• Every 8 weeks from randomization through 12 months

• Then every 12 weeks until progression or treatment discontinuation Primary endpoint

• Overall survival (OS) Enrolled patients

• Previously

treated advanced or metastatic clear-cell RCC

• 1 or 2 prior anti- angiogenic

treatments Randomize 1:1

Nivolumab (N = 410)

3 mg/kg every 2 weeks intravenous

Everolimus (N = 411) 10 mg/day

oral

• Treat until progression or intolerable toxicity

• Treatment beyond

progression was permitted if drug was tolerated and clinical benefit was noted

Randomized, open-labeled phase III study to compare nivolumab with everolimus in patients with advanced RCC after prior

systemic therapy (NCT01668784)

NIVOLUMAB

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NIVOLUMAB

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CheckMate 025:

A randomized, open-label, phase III study of nivolumab versus everolimus in advanced renal cell carcinoma

NIVOLUMAB

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CheckMate 025:

A randomized, open-label, phase III study of nivolumab versus everolimus in advanced renal cell carcinoma

NIVOLUMAB

25

5

0 5 10 15 20 25 30

Nivolumab Everolimus

Objective Response Rate (%)

P < 0.0001

 Patients on nivolumab treatment had a significantly better objective response rate than those on everolimus treatment

This means that more patients responded to treatment with nivolumab than to treatment with everolimus

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NIVOLUMAB

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NIVOLUMAB

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CABOZANTINIB

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CABOZANTINIB

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CABOZANTINIB

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CABOZANTINIB

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Pazienti

particolari ?

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Lunga

durata di I linea ?

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Rivalutazione marzo 2018:

Riduzione di malattia > 60% !!!

Paziente 42 aa

(settembre 2014 RCC con metastasi sincrone polmonari)

Sunitinib

Dicembre 2017

Nivolumab

CASO CLINICO

> 3 anni di I linea

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Paziente fragile?

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Quando lasciare Nivo ?

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Treatment Landscape for Metastatic RCC

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La terapia di seconda linea: TKI o immunoterapia?

Paziente 42 aa

Nivolumab

Seconda linea e oltre…

???