Revisione Oral Abstracts

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1 Revisione Oral Abstracts Francesco Massari Oncologia Medica Azienda Ospedaliero Universitaria di Bologna Policlinico S. Orsola-Malpighi UPDATES and NEWS from the Genitourinary Cancers Symposium - Milano,

2 Disclosures No pertinent C.O.I. with this presentation Advisory Boards/Honoraria/Consultant for: Astellas GSK Janssen Novartis Pfizer ProStrakan

3 Outline Health care outcomes in RCC Is surgery the best option for pts with resectable kidney cancer? What is the role of systemic therapy in pts M0?, Who are the best candidates for non surgical treatment of localized RCC?

4 Outline Abstract #502 Abstract #503

5 Outline Abstract #502 Abstract #503 Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

6 Background 20-30% patient with localized RCC develop metastatic disease Only clinical factors are used for prognastication Tumor variant Size Stage Symptoms No laboratory based biomarkers are used in regular clinical practice

7 Role of Tumor Infiltrating Immune Cells Tumor infiltrating immune cells have been shown to be of prognostic and even predictive value in ovarian, breast, colorectal and prostate cancer The prognostic impact of tumor immune cell infiltrates has not been reported in patients with localized ccrcc

8 Hypothesis and objectives Hypothesis: Increased overall immune cell infiltrates in localized ccrcc may suppress tumor cell and confer a lower risk of recurrence following surgery Objective: To study the association of morphologically identified immune cells with tumor recurrence in patients with localized ccrcc post nephrectomy Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

9 Methods Patients with ccrcc who underwent surgery for localized ccrcc Tumor recurrence data and a minimum follow up of 2 years Central pathology review by a single urologic pathologist blinded to recurrence outcomes Tumor pathologic variables (stage, grade, necrosis, histology) and intratumoral immune cell infiltration was recorded and graded Analyzed association of pathologic variables with recurrence Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

10 Central pathology review Tumor related variables Pathologic T stage Fuhrman grade Necrosis + vs - Histology Pure clear cell Clear cell with papillary features Clear cell with sarcomatoid features Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

11 Immune cell panel scoring Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

12 Central pathology review Immune cell infiltrate scoring: Dichotomous Low vs High Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

13 Central pathology review: Lymphocites/Plasma Cells Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

14 Central pathology review: Macrophages Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

15 Central pathology review: Neutrophils Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

16 Patient selection Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

17 Patient characteristics (1) Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

18 Patient characteristics (2) Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

19 Follow up and time to recurrence Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

20 Univariate analysis for association of baseline variables with objective tumor recurrence Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

21 Association between immune cell infiltration and other clinicopathologic variables Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

22 Multivariate analysis for association of baseline variables with objective tumor recurrence Higher pathological stage and increased immune cell infiltrate burden significally correlated with tumor recurrence Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

23 Most intra-tumoral immune cells in ccrcc may be immunosuppressive tumor-promoting PD1+ cells Significant decrease in circulating PD-1+ PBMCs after surgery for ccrcc Ineffective antitumor T cell response may be due to PD1 upregulation Harshman LC et al. Cancer J Jul-Aug;20(4):

24 Data bode well for the Phase III EA8143 trial planned ti study perioperative PD-1 Blockade for localized RCC Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

25 Conclusions Morphologically identified high intra-tumoral immune cell infiltration associated with increased risk of recurrence after controlling for clinicopathological factors following surgery for localized ccrcc AUTHOR HYPOTHESIS WAS NOT PROVEN! High immune cell infiltration associated with high grade and necrosis The strengths are central pathology review, excellent follow up, objective tumor recurrence as the clinical endpoint Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

26 Conclusions Data are hypothesis-generating and required validation The data are limited by the modest sample size of 159 patients, population with somewhat long median time to recurrence (indolent tumor biology) Molecular interrogation of immune and tumor cell may refine an immune panel that confers prognostic impact and may predict benefit from immunotherapy Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7

27 Outline Abstract #502 Abstract #503 de Velasco G et al J Clin Oncol 34, 2016 (suppl 2S; abstr 503) Poster Session C Board #D8

28 Background A significant minority of mrcc patients discontinue first-line VEGF- Targeted Therapy due toxicity Whether clinical outcomes differ in patients receiving second line targeted therapy based on the reason for discontinuation of first-line VEGF-Targeted Therapy is unknown 1. Motzer RJ et al. NEJM 2007; 2. Escudier B et allancet 2007; 3. Rini B et al. JCO 2008; 4. Motzer RJ et al NEJM 2013

29 Methods Patients were elegible if: They commenced a second line (2L) therapy after stopping first line (1L) VEGF-Targeted Therapy Reason for discontinuing 1L therapy were collected Treatment outcomes on 2L were compared by reasons for 1L discontinuation, adjusted for type of 2L therapy, time to 2L initiation, IMDC risk group, no. of metastasis at 2L To compare the outcomes of second-line mrcc patients depending on the reason for discontinuation of first-line VEGF- Targeted Therapy de Velasco G et al J Clin Oncol 34, 2016 (suppl 2S; abstr 503) Poster Session C Board #D8

30 Patient Population de Velasco G et al J Clin Oncol 34, 2016 (suppl 2S; abstr 503) Poster Session C Board #D8

31 Baseline Characteristic at First Line de Velasco G et al J Clin Oncol 34, 2016 (suppl 2S; abstr 503) Poster Session C Board #D8

32 Baseline Characteristic at Second Line de Velasco G et al J Clin Oncol 34, 2016 (suppl 2S; abstr 503) Poster Session C Board #D8

33 Response/Duration on Second Line Therapy de Velasco G et al J Clin Oncol 34, 2016 (suppl 2S; abstr 503) Poster Session C Board #D8

34 Overall Survival from start of second line de Velasco G et al J Clin Oncol 34, 2016 (suppl 2S; abstr 503) Poster Session C Board #D8

35 Overall Survival stratified by type of 2L therapy de Velasco G et al J Clin Oncol 34, 2016 (suppl 2S; abstr 503) Poster Session C Board #D8

36 Overall Survival stratified by duration from 1L to 2L initiation de Velasco G et al J Clin Oncol 34, 2016 (suppl 2S; abstr 503) Poster Session C Board #D8

37 Conclusions and limitations mrcc patients with discontinuation first-line VEGF-Targeted Therapy due to toxicity have better outcomes with second-line than patients who stop therapy because progression Limitations are the retrospective analysis and the selection bias (but consecutive patients). Did patients have PD before start of second line therapy? (G. Sonpavade Discussant) de Velasco G et al J Clin Oncol 34, 2016 (suppl 2S; abstr 503) Poster Session C Board #D8

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