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Revisione Oral Abstracts
UPDATES and NEWS from the Genitourinary Cancers Symposium - Milano, 22.01.16
Francesco Massari Oncologia Medica
Azienda Ospedaliero – Universitaria di Bologna
Policlinico S. Orsola-Malpighi
Disclosures
• No pertinent C.O.I. with this presentation
• Advisory Boards/Honoraria/Consultant for:
– Astellas
– GSK
– Janssen
– Novartis
– Pfizer
– ProStrakan
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?
Outline
• Abstract #502
• Abstract #503
Outline
• Abstract #502
• Abstract #503
Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7
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
Role of Tumor Infiltrating Immune Cells
• Tumor infiltrating immune cells have been shown to be of
prognostic and even predictive value in ovarian, breast, colo-
rectal and prostate cancer
• The prognostic impact of tumor immune cell infiltrates has not
been reported in patients with localized ccRCC
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
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 intra-
tumoral 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
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
Immune cell panel scoring
Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7
Central pathology review
Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7
• Immune cell infiltrate scoring: Dichotomous Low vs High
Central pathology review: Lymphocites/Plasma Cells
Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7
Central pathology review: Macrophages
Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7
Central pathology review: Neutrophils
Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7
Patient selection
Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7
Patient characteristics (1)
Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7
Patient characteristics (2)
Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7
Follow up and time to recurrence
Ghatalia P et al. J Clin Oncol 34, 2016 (suppl 2S; abstr 502) Poster Session C Board #D7
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
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
Multivariate 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
Higher pathological stage and increased immune cell infiltrate burden
significally correlated with tumor recurrence
Most intra-tumoral immune cells in ccRCC may be immunosuppressive tumor-promoting PD1+ cells
Harshman LC et al. Cancer J. 2014 Jul-Aug;20(4):272-80.
• Significant decrease in circulating PD-1+ PBMCs after surgery for ccRCC
• Ineffective antitumor T cell response may be due to PD1 upregulation
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
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
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
Outline
• Abstract #502
• Abstract #503
de Velasco G et al J Clin Oncol 34, 2016 (suppl 2S; abstr 503) Poster Session C Board #D8
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
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
Patient Population
de Velasco G et al J Clin Oncol 34, 2016 (suppl 2S; abstr 503) Poster Session C Board #D8
Baseline Characteristic at First Line
de Velasco G et al J Clin Oncol 34, 2016 (suppl 2S; abstr 503) Poster Session C Board #D8
Baseline Characteristic at Second Line
de Velasco G et al J Clin Oncol 34, 2016 (suppl 2S; abstr 503) Poster Session C Board #D8
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
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
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
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
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