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

2 2

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

3

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

Ove

rall

Su

rviv

al

(Pro

ba

bil

ity)

4

5

6

7

8

9

Lee et al, Ann Onc 2015

Bracarda et al, Ann Onc 2016

10

11

mRCC: I Line treatment IMDC risk Prognostic Score

12

13

14

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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21

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

25

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

28

29

mRCC I Line treatment Checkmate 214

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mRCC I Line treatment Checkmate 214

31

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

58

Slide 14

Presented By Neeraj Agarwal at 2019 ASCO Annual Meeting

60

Slide 15

Presented By Neeraj Agarwal at 2019 ASCO Annual Meeting

62

63

64 64

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 analysisb

Stratified 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)c

Confirmed 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