“Posters & Oral abstracts” - Aiom “Posters & Oral abstracts ... group 2 received a dose reduced to 400 or 600 mg/day after ... Choueiri TK et al ASCO GU 2017.

Francesco Atzori

Oncologia MedicaAzienda Ospedaliero Universitaria

Cagliari

Carcinoma renale “Posters & Oral abstracts”

Milano 3 marzo 2017

Renal Cell Cancer Track2017 Genitourinary Cancers Symposium

Poster Session (Selection)

Posters displayed: 101Italians (first author): 5

Renal Cell Cancer Track2017 Genitourinary Cancers Symposium

Poster Session (Selection)

Hot Topics (mRCC)

- TKIs: Dose, scheduling and factors (e.g.SNPs)

influencing outcome

-Immune Checkpoint Inhibitors (ICI): predictive &

prognostic factors, the importance of the microbiota

- Miscellaneous

Renal Cell Cancer Track2017 Genitourinary Cancers Symposium

Poster Session (Selection)

Hot Topics (mRCC)

- TKIs: Dose, scheduling and factors (e.g.SNPs)

influencing outcome

-Immune Checkpoint Inhibitors (ICI): predictive &

prognostic factors, the importance of the microbiota

- Miscellaneous

Bassanelli M. et al ASCO GU 2017

Lack of biomarkers for patients with mRCC affects clinical practice

Bassanelli M. et al ASCO GU 2017

Bassanelli M. et al ASCO GU 2017

Goal of the study and methodology

Bassanelli M. et al ASCO GU 2017

Patients Characteristics and clinical findings

Bassanelli M. et al ASCO GU 2017

Results

Example of Precision Medicine in action

Polymorphisms in ABCB1 and CYP3A5*3 are predictive of toxicity as hypertension, leukopenia and thrombocytopenia in pts with mRCC treated with sunitinib. The analysis of these

genetic variants may be useful for the selection and the optimization of the targeted therapy in mRCC pts.

Conclusions

Bassanelli M. et al ASCO GU 2017

Grassi P. et al ASCO GU 2017

Pazopanib is a standard treatment for metastatic renal cell

carcinoma (mRCC) and 800 mg/day is considered the optimal

dose for mRCC patients (pts).

However, some pts require a dose reduction due to toxicity. It

remains unclear whether reduced-dose pazopanib is as

effective as the standard dose in achieving a response.

Grassi P. et al ASCO GU 2017

BACKGROUND AND INTRODUCTION

Grassi P. et al ASCO GU 2017

PATIENTS AND METHODS

Retrospective evaluation of: treatment duration, objective response rate (ORR),

progression-free survival (PFS) and discontinuation rate in 69 pts with mRCC

treated with first-line pazopanib between 2011 and 2016

Three patient groups were compared: group 1 received the standard starting dose

of 800 mg/day daily, group 2 received a dose reduced to 400 or 600 mg/day after

starting with 800 mg/day due to grade 2-3 toxicity and group 3 received a reduced

starting dose of 400 or 600 mg/day because of ECOG performance status = 2

and/or comorbidities

Fig.2 Progression-free survival curves for groups 1 and 2 (groups 2+3) respectively

Fig.1 Progression-free survival curves for groups 1,2 and 3 respectively

Grassi P. et al ASCO GU 2017

RESULTS

Event incidence Hazard Ratio P-value

Group 1: 2.5 (95%CI 0.6-4.4) events/100person-month

1 0.343

Group 2 + 3: 3.9 (95%CI 0-14.3) events/100 person-month

1.43 (95%CI 0.68-2.98)

Our data suggest that mRCC pts receiving a lower

dose of first-line pazopanib might not have a

meaningful PFS advantage compared with those

receiving standard dose. These results highlight the

importance of management of the treatment-related

side effects that may eventually lead to optimal drug

exposure

Grassi P. et al ASCO GU 2017

CONCLUSIONS

Our data suggest that mRCC pts receiving a lower

dose of first-line pazopanib might not have a

meaningful PFS advantage compared with those

receiving standard dose. These results highlight the

importance of management of the treatment-related

side effects that may eventually lead to optimal drug

exposure

Grassi P. et al ASCO GU 2017

CONCLUSIONS

Any other useful method to calculate the right dose?

Renal Cell Cancer Track2017 Genitourinary Cancers Symposium

Poster Session (Selection)

Hot Topics (mRCC)

- TKIs: Dose, scheduling and factors (e.g.SNPs)

influencing outcome

-Immune Checkpoint Inhibitors (ICI): predictive &

prognostic factors, the importance of the microbiota

- Miscellaneous

Courtesy of Lisa Derosa

Courtesy of Lisa Derosa

Courtesy of Lisa Derosa

Courtesy of Lisa Derosa

Courtesy of Lisa Derosa

Courtesy of Lisa Derosa

Courtesy of Lisa Derosa

To come: solving the misteries of the gut microbiota

Renal Cell Cancer Track2017 Genitourinary Cancers Symposium

Poster Session (Selection)

Hot Topics (mRCC)

- TKIs: Dose, scheduling and factors (e.g.SNPs)

influencing outcome

-Immune Checkpoint Inhibitors (ICI): predictive &

prognostic factors, the importance of the microbiota

- Miscellaneous

Alleluia!!!

A SINGLE-ARM BIOMARKER-BASED PHASE II TRIAL OF SAVOLITINIB INPATIENTS WITH ADVANCED PAPILLARY

RENAL CELL CANCERAbstract 436

Choueiri TK et al ASCO GU 2017

−Of the non-clear cell renal carcinomas, papillary RCC (PRCC) is the

most common with no drug approved for specifically for PRCC

−MET and its ligand, hepatocyte growth factor, are known to play an

important role in the molecular events underlying oncogenesis in

PRCC1,2

−Savolitinib (AZD6094, HMPL-504, volitinib) is a potent, selective

MET inhibitor which has shown activity in patients with MET-driven

PRCC in a phase I study3

−A phase II study of savolitinib for patients with PRCC, in whom anti-

tumor activity was correlated with MET pathway alterations is

reported (Clinicaltrials.gov identifier: NCT02127710)

Choueiri TK et al ASCO GU 2017

BACKGROUND AND INTRODUCTION

PATIENTS AND METHODS

− Single-arm, multicenter, global, phase II study designed to evaluate the

safety and efficacy of savolitinib (600 mg orally daily) in patients with PRCC,

irrespective of prior treatment

− Primary objective: to assess the objective response rate (ORR) to savolitinib

in all patients with PRCC and by MET status

− Secondary objectives: change in target lesion tumor size from baseline,

progression-free survival (PFS) and duration of response (DoR)

− Key inclusion criteria: histologically confirmed locally advanced or metastatic

PRCC, predicted life expectancy ≥12 weeks, age ≥18 years and

adequatehematologic, hepatic and renal function

− Exclusion criteria: prior or current MET inhibitor treatment

Choueiri TK et al ASCO GU 2017

RESULTS

Choueiri TK et al ASCO GU 2017

RESULTS

Choueiri TK et al ASCO GU 2017

SUMMARY AND CONCLUSIONS

−8 of 44 (18%) patients with MET- driven PRCC achieved a

PR

−PFS was significantly longer in patients with MET-driven

PRCC compared with MET-independent disease (6.2 versus

1.4 months, respectively (p<0.0001)

−Treatment with savolitinib was generally well tolerated, with

the majority of AEs being grade 1 or 2

−These data support the hypothesis that savolitinib has anti-

tumor activity in patients with MET-driven PRCC Choueiri TK et al ASCO GU 2017

Grazie per l’attenzione