Carcinoma renale. Francesco Atzori. Oncologia Medica Azienda Ospedaliero Universitaria Cagliari. Posters & Oral abstracts

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1 Carcinoma renale Posters & Oral abstracts Francesco Atzori Oncologia Medica Azienda Ospedaliero Universitaria Cagliari Milano 3 marzo 2017

2 Renal Cell Cancer Track 2017 Genitourinary Cancers Symposium Poster Session (Selection) Posters displayed: 101 Italians (first author): 5

3 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

4 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

5 Bassanelli M. et al ASCO GU 2017

6 Lack of biomarkers for patients with mrcc affects clinical practice Bassanelli M. et al ASCO GU 2017

7 Goal of the study and methodology Bassanelli M. et al ASCO GU 2017

8 Patients Characteristics and clinical findings Bassanelli M. et al ASCO GU 2017

9 Results Bassanelli M. et al ASCO GU 2017

10 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

11 Grassi P. et al ASCO GU 2017

12 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

13 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

14 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 ) events/100 person-month Group 2 + 3: 3.9 (95%CI ) events/100 person-month (95%CI ) Grassi P. et al ASCO GU 2017

15 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

16 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?

17 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

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19 Courtesy of Lisa Derosa

20 Courtesy of Lisa Derosa

21 Courtesy of Lisa Derosa

22 Courtesy of Lisa Derosa

23 Courtesy of Lisa Derosa

24 Courtesy of Lisa Derosa

25 To come: solving the misteries of the gut microbiota Courtesy of Lisa Derosa

26 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

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28 Alleluia!!!

29 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

30 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: NCT ) Choueiri TK et al ASCO GU 2017

31 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

32 RESULTS Choueiri TK et al ASCO GU 2017

33 RESULTS Choueiri TK et al ASCO GU 2017

34 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

35 Grazie per l attenzione