Carcinoma papilar renal, cromófobo y otras histologías. Maria José Méndez Vidal Servicio de oncología Medica Hospital Reina Sofía Córdoba

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1 Carcinoma papilar renal, cromófobo y otras histologías. Maria José Méndez Vidal Servicio de oncología Medica Hospital Reina Sofía Córdoba

2 Europe new cases RCC 2012, affected men Slide 3 collecting duct, renal medullary, Translocation unclassified carcinomas. Sarcomatoide variant not distinct histology entity, high grade transformation Ramaprasad Srinivasan Genitourinary Cancers Symposium 2016

3 Human Renal Epithelial Neoplasms Ramaprasad Srinivasan Genitourinary Cancers Symposium 2016

4 2015 un año importante para NCCRCC Tumores muy heterogéneos. Excluidos de los estudios de registro Opción de tratamiento prioritaria: ensayos clínicos. Progresos caracterización molecular Publicación de primeros estudios aleatorizados.

5 The Cancer Genome Atlas (TCGA) Project ( ) Presented By Gabriel Malouf at Genitourinary Cancers Symposium 2016

6 Refined classification reflects the genotypic and phenotypic differences among the various types of these tumors and may lead to more appropriate clinical management and development of more effective forms of therapy. N engl J Med 374;2 January 14,

7 MET mutations 15% (10/65) of prcc samples and included previously unreported recurrent activating mutations. In chrcc, TP53, PTEN, FAAH2, PDHB, PDXDC1 Nat Genet (1)

8 Targeting VHL/HIF in Clear Cell RCC Presented By Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

9 Papillary RCC: Histologic Subtypes Presented By Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

10 Hereditary Papillary Renal Cancer (HPRC) Presented By Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

11 Met Activation in Sporadic Papillary RCC Presented By Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

12 Slide 15 Presented By Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

13 Slide 17 Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

14 Slide 18 Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

15 Germline MET Mutations Associated with High Response Rate Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

16 <br />Met Inhibitors in Papillary RCC: <br />Summary Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

17 Slide 23 Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

18 Hereditary Leiomyomatosis <br />Renal Cell Carcinoma: HLRCC Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

19 Slide 26 Presented By Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

20 Slide 28 Presented By Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

21 Slide 31 Presented By Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

22 Slide 32 Presented By Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

23 Slide 34 Presented By Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

24 Slide 35 Presented By Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

25 Slide 36 Presented By Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

26 Slide 37 Presented By Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

27 Slide 39 Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

28 Slide 41 Presented By Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

29 Bevacizumab plus Erlotinib<br /><br />HLRCC Associated Kidney Cancer<br /> Presented By Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

30 Bevacizumab plus Erlotinib<br /><br />Sporadic Papillary RCC<br /> Presented By Ramaprasad Srinivasan at Genitourinary Cancers Symposium 2016

31 Eur Urol 2015 (68)

32

33

34 The overall response rate for non-ccrcc with targeted agents was 10.5%. In studies directly comparing non-ccrcc and ccrcc, there were significantly lower response rates for non-ccrcc For non-ccrcc treated with targeted agents. median PFS and OS were 7.4 and 13.4 mo, respectively; for patients with ccrcc, these were 10.5 mo and 15.7 mo

35

36 Slide 5 Ramaprasad Srinivasan Genitourinary Cancers Symposium 2016

37 108 pts 72 analysis Everolimus no superior to sunitinib. 17,6 sarcomatoide Modest efficacy. Interim analysis favoring sunitinib vs everolimus

38 ESPN: Trial Design Presented By Lisa Pickering at Genitourinary Cancers Symposium 2016

39 ASPEN: Prolonged PFS With Sunitinib vs Everolimus in Nonclear-Cell RCC Lancet Oncol 2016 Published Online January 12, 2016

40 ASPEN: Trial Design Presented By Lisa Pickering at Genitourinary Cancers Symposium 2016

41 ASPEN: Pt Baseline Characteristics Characteristic Sunitinib (n = 51) Everolimus (n = 57) Male, % Median age, yrs (range) 59 (24-100) 64 (29-90) Papillary histology (type 1), % 65 (8) 65 (4) Chromophobe, % Unclassified histology, % Translocation carcinoma, % 12 4 Sarcomatoid differentiation, % Prior nephrectomy, % MSKCC risk group, % Armstrong AJ, et al. ASCO Abstract

42 Probability of PFS ASPEN: Progression-Free Survival Sunitinib, median PFS 8.3 mos Everolimus, median PFS 5.6 mos Stratified log-rank HR 1.41, P =.16 < 0.20 boundary P value Pts at Risk, n Sunitinib Everolimus Mos Median OS: sunitinib vs everolimus: 32 (95% CI: 15-NR) vs 13 mos (95% CI: 10-38) (HR: 1.12; P =.60) Armstrong AJ, et al. ASCO Abstract Reprinted with permission

43 ASPEN: PFS by Prespecified Pt Subgroups Category Median PFS (S vs. E, mos) HR (80% CI) Overall 8.3 vs ( ) Good risk 14 vs ( ) Int. Risk 6.5 vs ( ) Poor Risk 4.0 vs ( ) Papillary 8.1 vs ( ) Chromophobe 5.5 vs ( ) Unclassified 11.5 vs ( ) HR and 80% CI Favors everolimus Favors sunitinib Armstrong AJ, et al. ASCO Abstract Reprinted with permission.

44 ASPEN: Tumor Response by RECIST 1.1 Response Best overall response, % CR/PR SD PD Not evaluated Clinical benefit response (CR + PR + SD 24 wks), % Sunitinib (n = 51) Everolimus (n = 57) Sunitinib associated with larger clinical response but more tumor growth Best tumor change, median % Median duration of response, mos Armstrong AJ, et al. ASCO Abstract 4507.

45 ASPEN: Conclusions Sunitinib significantly prolonged PFS compared to everolimus in previously untreated metastatic NCRCC Pts with MSKCC good/intermediate risk status, papillary histology, and unclassified subtype had improved PFS with sunitinib Pts with MSKCC poor risk status and chromophobe histology had improved PFS with everolimus Short survival times and low response rates to both agents highlight continuing medical need for new treatment approaches in this pt population Armstrong AJ, et al. ASCO Abstract 4507.

46 ESPN & ASPEN, Summary of efficacy results Lisa Pickering at Genitourinary Cancers Symposium 2016

47 Los tumores no células claras constituyen un grupo heterogeneo enfermedades. resultados de estudios randomizados: ESPN, ASPEN Sunitinib mejor PFS que everolimus. Algunos subgrupos se podrían beneficiar de tto. con mtor (mal pronóstico y cromófobos). Resultados modestos en PFS y SG. Se precisan tratamientos individualizados para mejorar pronóstico. Terapias dirigidas eficaces en subgrupos con mutaciones via MET y FH

48

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