I tumori del rene: Trattamento di I linea - AIOM...Cytoreductive nephrectomy, Metastasectomy and post-operative treatment Active surveillance Medical Treatments: Perspectives VEGFR-TKI/Immunotherapy

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

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

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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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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


Patient characteristics (2) / classification by IMDC


Median Overall Survival (ITT), FU = 61.5 months


Slide 20


Median Overall Survival (ITT) Intermediate patients


Median OS (ITT) patients with 1 metastatic site vs >1


Secondary nephrectomy in Arm B (sunitinib alone)


Slide 32


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Slide 14

Presented By Neeraj Agarwal at 2019 ASCO Annual Meeting

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Slide 15


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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


IMDC Intermediate/Poor Risk: OS, PFS, and ORR


PFS: Presence of Sarcomatoid Featuresa


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.


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.


Efficacy of therapy is improving…


cc mRCC: I Line treatment Conclusions

What we know now…



1L Combination Therapy Trials of Approved Agents

Presented By Rana McKay at 2019 ASCO Annual Meeting


1L Combination Therapy Trials – ITT

Presented By Rana McKay at 2019 ASCO Annual Meeting


Slide 22


Slide 23


Sunitinib in mRCC with Brain Mets: Results from the Global Expanded Access Protocol


Slide 25


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I tumori del rene: Trattamento di I linea - AIOM...Cytoreductive nephrectomy, Metastasectomy and post-operative treatment Active surveillance Medical Treatments: Perspectives VEGFR-TKI/Immunotherapy