revisione oral abstractsmedia.aiom.it/userfiles/files/doc/aiom-servizi/20160122mi_73_massari.pdf ·...

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


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


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


Immune cell panel scoring


Central pathology review


• Immune cell infiltrate scoring: Dichotomous Low vs High

Central pathology review: Lymphocites/Plasma Cells


Central pathology review: Macrophages


Central pathology review: Neutrophils


Patient selection


Patient characteristics (1)


Patient characteristics (2)


Follow up and time to recurrence


Univariate analysis for association of baseline variables with objective tumor recurrence


Association between immune cell infiltration and other clinicopathologic variables


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

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


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


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


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


Baseline Characteristic at First Line


Baseline Characteristic at Second Line


Response/Duration on Second Line Therapy


Overall Survival – from start of second line


Overall Survival stratified by type of 2L therapy


Overall Survival stratified by duration from 1L to 2L initiation


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)


[email protected]

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