Download Renal Cell Carcinoma Case Studies

Carcinoma renale
“Posters & Oral abstracts”
Francesco Atzori
Oncologia Medica
Azienda Ospedaliero Universitaria
Cagliari
Milano 3 marzo 2017
Renal Cell Cancer Track
2017 Genitourinary Cancers Symposium
Poster Session (Selection)
Posters displayed: 101
Italians (first author): 5
Renal Cell Cancer Track
2017 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 Track
2017 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
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
Bassanelli M. et al ASCO GU 2017
Conclusions
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.
Bassanelli M. et al ASCO GU 2017
Example of Precision Medicine in action
Grassi P. et al ASCO GU 2017
BACKGROUND AND INTRODUCTION
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
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
Grassi P. et al ASCO GU 2017
RESULTS
Fig.1 Progression-free survival curves for groups 1,2 and 3
respectively
Fig.2 Progression-free survival curves for groups 1 and 2
(groups 2+3) respectively
Event incidence
Hazard Ratio
P-value
Group 1: 2.5 (95%CI 0.6-4.4) events/100
person-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)
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
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
Any other useful method to calculate the right dose?
Renal Cell Cancer Track
2017 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
To come: solving the misteries of the gut microbiota
Courtesy of Lisa Derosa
Renal Cell Cancer Track
2017 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 CANCER
Abstract 436
Choueiri TK et al ASCO GU 2017
BACKGROUND AND INTRODUCTION
−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 antitumor activity was correlated with MET pathway alterations is
reported (Clinicaltrials.gov identifier: NCT02127710)
Choueiri TK et al ASCO GU 2017
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 antitumor activity in patients with MET-driven PRCC
Choueiri TK et al ASCO GU 2017
Grazie per l’attenzione