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
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
Choice of 2nd 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
Strategie terapeutiche a confronto in II linea
Nivo ?
Cabo ? Axi ?
Strategie terapeutiche a confronto in II linea
AXITINIB
AXITINIB
Stato dell’arte AXITINIB
AXITINIB
Strategie terapeutiche a confronto in II linea
Strategie terapeutiche a confronto in II linea
Strategie terapeutiche a confronto in II linea
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
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
NIVOLUMAB
CheckMate 025:
A randomized, open-label, phase III study of nivolumab versus everolimus in advanced renal cell carcinoma
NIVOLUMAB
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
NIVOLUMAB
NIVOLUMAB
CABOZANTINIB
CABOZANTINIB
CABOZANTINIB
CABOZANTINIB
Strategie terapeutiche a confronto in II linea
Strategie terapeutiche a confronto in II linea
Strategie terapeutiche a confronto in II linea
Strategie terapeutiche a confronto in II linea
Pazienti
particolari ?
Strategie terapeutiche a confronto in II linea
Strategie terapeutiche a confronto in II linea
Strategie terapeutiche a confronto in II linea
Lunga
durata di I linea ?
Strategie terapeutiche a confronto in II linea
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
Strategie terapeutiche a confronto in II linea
Paziente fragile?
Strategie terapeutiche a confronto in II linea
Strategie terapeutiche a confronto in II linea
Quando lasciare Nivo ?
Strategie terapeutiche a confronto in II linea
Strategie terapeutiche a confronto in II linea
Treatment Landscape for Metastatic RCC
Strategie terapeutiche a confronto in II linea
Strategie terapeutiche a confronto in II linea
Strategie terapeutiche a confronto in II linea