I tumori del rene:
Trattamento di I linea
Novità diagnostico terapeutiche nel carcinoma renale e prostatico Campobasso, 19 Settembre 2019
Enrico Ricevuto & Gemma Bruera Assistenza Oncologica Territoriale Ospedale S. Salvatore L’Aquila Rete Oncologica ASL1 Abruzzo
Dipartimento Scienze Cliniche Applicate e Biotecnologiche
Università dell’Aquila
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mRCC: I Line Treatment Options
Medical Treatments
VEGFR-TKI: Sunitinib, Pazopanib, Tivozanib
Immunotherapy: Nivolumab/Ipilimumab
MET-Inhibitors: Cabozantinib
Cytoreductive nephrectomy, Metastasectomy and post-operative treatment
Active surveillance
Medical Treatments: Perspectives
VEGFR-TKI/Immunotherapy Associations:
Pembrolizumab/Axitinib
Atezolizumab/Bevacizumab
Avelumab/Sunitinib
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A retrospective study utilizing 2000–2010 SEER data evaluated changes in survival between pre-targeted therapy and targeted therapy periods in advanced RCC
Patients in the targeted therapy era showed improved survival compared with those diagnosed in the pretarget therapy era (HR, 0.86, P<0.01)
Overall Survival in the Pre-targeted Therapy vs Targeted Therapy Eras
HR, hazard ratio; RCC, renal cell carcinoma; SEER, Surveillance, Epidemiology, and End Results.
Li P et al. Cancer Med 2016;5:169–81.
Pretarget Era (2000–2005): N=7,231 Targeted Era (2006–2010): N=6,439
Years 0
0.25 0.50 0.75 1.00
1 2 3 4 5 6
Overall Survival, Advanced RCC
Overall Survival (Probability)
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Lee et al, Ann Onc 2015
Bracarda et al, Ann Onc 2016
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mRCC: I Line treatment
IMDC risk Prognostic Score
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mRCC: I Line treatment
Checkmate 214
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mRCC: I Line treatment
Checkmate 214, Baseline Characteristics
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mRCC I Line treatment
Checkmate 214: IMDC Intermediate/Poor, OR/DOR
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mRCC I Line treatment
Checkmate 214: IMDC Intermediate/Poor, PFS/IRRC
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mRCC I Line treatment
Checkmate 214: IMDC Intermediate/Poor, OS
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mRCC I Line treatment
Checkmate 214: ITT, ORR/PFS/OS
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mRCC I Line treatment
Checkmate 214: Activity by PDL1 expression
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mRCC I Line treatment
Checkmate 214: IMDC Intermediate/Poor, PFS by PDL1
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mRCC I Line treatment
Checkmate 214: Responders, OS/TTR/TTP/Duration of therapy
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mRCC I Line treatment
Checkmate 214: Sarcomatoid, Intermediate/Poor, OR
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mRCC I Line treatment
Checkmate 214: Sarcomatoid, IMDC Intermediate/Poor, PFS IA
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mRCC I Line treatment
Checkmate 214: Sarcomatoid, IMDC Intermediate/Poor, OS
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mRCC I Line treatment
Checkmate 214
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mRCC I Line treatment
Checkmate 214
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mRCC I Line treatment
Checkmate 214
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mRCC I Line treatment
Checkmate 214
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mRCC I Line treatment
Checkmate 214
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mRCC I Line treatment
Checkmate 214
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mRCC I Line treatment
Checkmate 214
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mRCC I Line treatment
Checkmate 214
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cc mRCC: I Line treatment
Options
Slide 21
Presented By Robert Uzzo at 2019 ASCO Annual Meeting
CARMENA: Prospective, multicenter, open-label, randomized, phase 3 non-inferiority study
Presented By Arnaud Mejean at 2019 ASCO Annual Meeting
Slide 11
Presented By Arnaud Mejean at 2019 ASCO Annual Meeting
Patient characteristics (2) / classification by IMDC
Presented By Arnaud Mejean at 2019 ASCO Annual Meeting
Median Overall Survival (ITT), FU = 61.5 months
Presented By Arnaud Mejean at 2019 ASCO Annual Meeting
Slide 20
Presented By Arnaud Mejean at 2019 ASCO Annual Meeting
Median Overall Survival (ITT) Intermediate patients
Presented By Arnaud Mejean at 2019 ASCO Annual Meeting
Median OS (ITT) patients with 1 metastatic site vs >1
Presented By Arnaud Mejean at 2019 ASCO Annual Meeting
Secondary nephrectomy in Arm B (sunitinib alone)
Presented By Arnaud Mejean at 2019 ASCO Annual Meeting
Slide 32
Presented By Arnaud Mejean at 2019 ASCO Annual Meeting
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Slide 14
Presented By Neeraj Agarwal at 2019 ASCO Annual Meeting
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Slide 15
Presented By Neeraj Agarwal at 2019 ASCO Annual Meeting
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mRCC: I Line Treatment Options
Medical Treatments
VEGFR-TKI: Sunitinib, Pazopanib, Tivozanib
Immunotherapy: Nivolumab/Ipilimumab
MET-Inhibitors: Cabozantinib
Cytoreductive nephrectomy, Metastasectomy and post-operative treatment
Active surveillance
Medical Treatments: Perspectives
VEGFR-TKI/Immunotherapy Associations:
Pembrolizumab/Axitinib
Atezolizumab/Bevacizumab
Avelumab/Sunitinib
Efficacy of therapy is improving…
Presented By Bradley McGregor at 2019 ASCO Annual Meeting
mRCC: I Line treatment
Conclusions
861
(FASE3)
KPS < 80% -Interval from diagnosis to metastatic disease < 12months -Corrected serum calcium >10 mg/dl - Platelets > ULN - Neutrophils > ULN - Low Hb
KEYNOTE-426: OS in the ITT Population
Presented By Brian Rini at 2019 ASCO Annual Meeting
IMDC Favorable Risk: OS, PFS, and ORR
Presented By Brian Rini at 2019 ASCO Annual Meeting
IMDC Intermediate/Poor Risk: OS, PFS, and ORR
Presented By Brian Rini at 2019 ASCO Annual Meeting
PFS: Presence of Sarcomatoid Featuresa
Presented By Brian Rini at 2019 ASCO Annual Meeting
IMmotion151 Study Design
Key eligibility
• Treatment-naive advanced or metastatic RCC
• Clear cell and/or sarcomatoid histology
• KPS ≥ 70
• Tumor tissue available for PD-L1 staining
R 1:1
Atezolizumab 1200 mg IV q3w +
Bevacizumab 15 mg/kg IV q3w
Sunitinib 50 mg PO QD (4 weeks on, 2 weeks off)
N = 915
Stratification
•MSKCC risk score
•Liver metastases
•PD-L1 IC IHC status (< 1% vs ≥ 1%)a
Co-primary endpoints
• PFS by INV assessment in PD-L1+
• OS in ITT
Other key endpoints
• PFS in ITT
• OS in PD-L1+
• ORR
• Patient-reported outcomes
• Safety
IC, tumor-infiltrating immune cell; IHC, immunohistochemistry; INV, investigator; IRC, independent review committee; ITT, intent-to-treat; IV, intravenous; ORR, overall response rate; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival; PO, by mouth; R, randomized; RCC, renal cell carcinoma; KPS, Karnofsky Performance Status; MKSCC, Memorial Sloan
Kettering Cancer Center; q3w, every 3 weeks; QD, once a day.
a 40% prevalence using SP142 IHC assay.
Motzer RJ, et al. ASCO GU 2018 [abstract 578].
Progression-Free Survival in the PD-L1+
Population
Median PFS, mo (95% CI) Atezo + Bev 11.2 (8.9, 15.0) Sunitinib 7.7 (6.8, 9.7)
HR, 0.74 (95% CI: 0.57, 0.96) P = 0.02a
PFS assessed by investigators. Minimum follow- up, 12 months. Median follow-up, 16 months.
a The PFS analysis passed the pre-specified P value boundary of α = 0.04.
Motzer RJ, et al. ASCO GU 2018 [abstract 578].
Efficacy Summary
PD-L1+ ITT
Atezo + Bev n = 178
Sunitinib n = 184
Atezo + Bev n = 454
Sunitinib n = 461a
Median PFS, mo (95% CI)
Stratified HR, (95% CI)
11.2 (8.9, 15.0) 7.7 (6.8, 9.7) 11.2 (9.6, 13.3) 8.4 (7.5, 9.7)
0.74 (0.57, 0.96) 0.83 (0.70, 0.97)
Overall survival, mo
Interim analysisbStratified HR, (95% CI)
Not reached 23.3 (21.3, NR) Not reached Not reached
0.68 (0.46, 1.00) 0.81 (0.63, 1.03)
cConfirmed ORR, % (95% CI)
Complete response
43% (35, 50)
9%
35% (28, 42)
4%
37% (32, 41)
5%
33% (29, 38)
2%
a n = 460 for ORR analysis.
b Event/patient ratio: PD-L1+, atezo + bev, 25% and sunitinib, 35%; ITT, atezo + bev, 27% and sunitinib, 31%.
c P = 0.09. The OS analysis did not pass the P value boundary of α = 0.0009 at the first interim analysis.
Response and progression assessed by investigator; minimum follow-up, 12 months. Median follow-up, 15 months.
Motzer RJ, et al. ASCO GU 2018 [abstract 578].
Efficacy of therapy is improving…
Presented By Bradley McGregor at 2019 ASCO Annual Meeting
cc mRCC: I Line treatment
Conclusions
What we know now…
Presented By Bradley McGregor at 2019 ASCO Annual Meeting
cc mRCC: I Line treatment
Conclusions
1L Combination Therapy Trials of Approved Agents
Presented By Rana McKay at 2019 ASCO Annual Meeting
cc mRCC: I Line treatment
Conclusions
1L Combination Therapy Trials – ITT
Presented By Rana McKay at 2019 ASCO Annual Meeting
cc mRCC: I Line treatment
Conclusions
Slide 22
Presented By Neeraj Agarwal at 2019 ASCO Annual Meeting
Slide 23
Presented By Neeraj Agarwal at 2019 ASCO Annual Meeting
Sunitinib in mRCC with Brain Mets: Results from the Global Expanded Access Protocol
Presented By Neeraj Agarwal at 2019 ASCO Annual Meeting
Slide 25
Presented By Neeraj Agarwal at 2019 ASCO Annual Meeting