renal cancer treatment

1. AIOM POST ASCO GU REVIEW
Milano 2 marzo 2018
Roberto Sabbatini
Azienda Ospedaliero Universitaria
Policlinico di Modena
UPDATES and NEWS from the Genitourinary Cancers Symposium
Carcinoma Renale
Highlights

2. Study Design
IMmotion 151: a randomized phase III study of
Atezolizumab plus Bevacizumab vs Sunitinib in
untreated mRCC
Primary endopints: - PFS by investigator-assessment in PD-L1+ pts defined as ≥ 1% expression on IC
- OS in ITT
Motzer R., et al ASCO-GU 2018

3. Baseline Characteristics
IMmotion 151: a randomized phase III study of
Atezolizumab plus Bevacizumab vs Sunitinib in
untreated mRCC
Motzer R., et al ASCO-GU 2018
Tumor PD-L1 expression and infiltrating PD-1–positive cell
status in sarcomatoid and nonsarcomatoid ccRCC.
Kawakami F, et al. Cancer 2017

4. Progression-Free Survival in PD-L1+
Motzer R., et al ASCO-GU 2018
IMmotion 151: a randomized phase III study of Atezolizumab
plus Bevacizumab vs Sunitinib in untreated mRCC

5. Objective Response Rate
IMmotion 151: a randomized phase III study of Atezolizumab
plus Bevacizumab vs Sunitinib in untreated mRCC
Motzer R., et al ASCO-GU 2018

6. PFS in Key Subgroups (PD-L1+)
IMmotion 151: a randomized phase III study of Atezolizumab
plus Bevacizumab vs Sunitinib in untreated mRCC
Motzer R., et al ASCO-GU 2018

7. Overall Survival in ITT
Motzer R., et al ASCO-GU 2018
IMmotion 151: a randomized phase III study of Atezolizumab
plus Bevacizumab vs Sunitinib in untreated mRCC

8. Safety Summary in All-Treated Patients
Treatment-related AEs
Safety results wre similar in all-treated pts and in those with PD-
L1+ disease
16% of pts treated with ATEZO/BEVA required
systemic corticosteroid use within 30 days of an AE of
special interest
AE of Special interest
IMmotion 151: Adverse Events
Motzer R., et al ASCO-GU 2018

9. IMmotion 151 and CheckMate 214: efficacy
Atezo/Beva ChecKMate 214
PD-L1+ ITT Intermediate/p
oor
ITT
n. 178 454 425 550
mFU, mos 15 25.2
mPFS, mos 11.2 11.2 11.6 12.4
mOS, mos
(95%, CI)
NR NR NR NR
HR
(95%, CI)
0.68
(0.46-1.00)
0.81
(0.63-1.03)
0.63
(0.44-0.89)
0.68
(0.49-0.95)
ORR % 43 37 42* 39*
CR% 9 5 9 NA
*IRC

10. Slide 4
51 treatment-naive pts with aRCC were enrolled and
received treatment:
- 11 pts in the dose-finding phase
- 41 pts in the dose-expansion phase
Safety and efficacy of axitinib in combination with
pembrolizumab in pts with advanced RCC (aRCC)
Atkins MB, et al, ASCO-GU 2018

11. Median time to response was 2.8 ,os (range 0.7-15.2); mDOR was 18.6 mos (95% CI 15.1-not reached); 10 pts
who discontinued both drugs due to toxicity were censored even though theri disease had not progressed (5 were
still responding to treatment)
Atkins MB, et al, ASCO-GU 2018
Tumor Response

12. Outcome
Estimate Progression-free survival Estimate Overall survival
Atkins MB, et al, ASCO-GU 2018
mOS was not reached at minimum follow-up period of 17.6 mos; 6 death were registered (disease
under study and other reason)

13. First line Trials: Progression-Free Survival
PD-L1+
Intermediate/
poor risk
Comparz
Trial Comparz
Trial
Phase Ib
Intermediate/
poor risk

14. Phase 3 VEGF/PD-1 blockade combination trials

15. Multicenter, randomized, open-label, Phase 3 study to
compare the efficacy and safety of lenvatinib in combination
with everolimus or pembrolizumab vs sunitinib as first-line
treatment in subjects with advanced RC
• Primary endpoint: PFS (by IRC) using RECIST 1.1with lenvatinib ± everolimus
vs everolimus alone
• Secondary endpoints: ORR, OS, Safety and tolerability, QoL PFS with
combination vs lenvatinib, ORR, OS, safety
Lenvatinib 18 mg QD +
Everolimus 5 mg QD
Measurable metastatic
or advanced RCC with a
clear cell component;
KPS ≥ 70%
Lenvatinib 20 mg QD +
Pembrolizumab 200 mg
Sunitinib 50 mg QD
Treated until PD or
unacceptable
toxicity
735
pts

16. Slide 5
Homologous Repair Deficiency in VHL-mutated
Clear Cell Renal Cell Carcinoma
Patrick P, et al ASCO-GU 2018
• VHL loss leads to geneomic instability early in ccRCC carcinogenesis
• Early ccRCC tumors display defect in DNA damage response signaling and increased presence of a functional HR
deficient signature
• HR deficient signature predicts for improved OS in ccRCC
• Future studies of integrated biomarkers of HR deficient to select ccRCC pts for DDR inhibitor-based therapy are
warrented

17. Key design features of EORTC 90101 “CREATE”
• Only 27 (65.9%) had centrally confirmed PRCC1
• Median age 62.5 yrs, 43.5% had an ECOG PS of 1 and 82.7% had prior surgery
• Only 39.1% (9/23) had received prior systemic therapy
Crizotinib in pts with advanced PRCC1 with MET mutations or
amplification: Finale results of EORTC90101 “CREATE”
Schoffski P, et al. ASCO-GU 2018; abs 201511

18. Maximum shrinkage of RECIST target lesions in the
MET+, MET-, and MET? sub-cohorts
Schoffski P, et al. ASCO-GU 2018; abs 201511
Crizotinib un pts with advanced PRCC1 with MET mutations
or amplification: Finale results of EORTC90101 “CREATE”

19. Gut microbiome composition and response to
sunitinib in mRCC
Gong J, et al. ASCO –GU 2018; abs 657

20. roberto.sabbatini@unimore.it