Emerging strategies and controversial topics in advanced...

Cinzia Ortega Oncologia

ASLCN2 Alba-Bra

Emerging strategies and controversial topics

in advanced prostate cancer: Highlights

Outline

• Emerging Immunotherapy Strategies for Castrate Resistant Prostate Cancer

• Management of Oligometastatic Prostate Cancer From Imaging to Therapy

• Abstract 165: The FALCON trial – impact of 18F-fluciclovina PET/CT on clinical management choices for men with biochemically recurrente prostate cancer

• Local Treatment in Patients with Newly Diagnosed Metastatic Disease - Debates on Controversial Topics in Prostate Cancer (ARS)

Outline

• Emerging Immunotherapy Strategies for Castrate Resistant Prostate Cancer

• Management of Oligometastatic Prostate Cancer From Imaging to Therapy

• Abstract 165: The FALCON trial – impact of 18F-fluciclovina PET/CT on clinical management choices for men with biochemically recurrente prostate cancer

• Local Treatment in Patients with Newly Diagnosed Metastatic Disease - Debates on Controversial Topics in Prostate Cancer (ARS)

Immune Checkpoint Inhibition in Prostate Cancer

Presented By Fatima Karzai at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care (Modified)

• Two negative ipilimumab phase 3 studies

• No data supporting anti PD-1/PD-L1 monoterapy in PC

Courtesy of K. Fizazi

PC is poorly infiltrated by immune cells

Presented By Padmanee Sharma at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

IPI drives T cell responses

Slide 17

Presented By Padmanee Sharma at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

IPILIMUMAB enhances PD-L-1 and VISTA expression in PC

Presented By Padmanee Sharma at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary

Care

IPI-NIVO Combo

To Sergio Bracarda

• Immunotherapy in PC: low mutational load Could it be a potential good treatment?

• When immunotherapy in PC continuum?

• Endpoint: long responders?

Outline

• Emerging Immunotherapy Strategies for Castrate Resistant Prostate Cancer

• Management of Oligometastatic Prostate Cancer From Imaging to Therapy

• Abstract 165: The FALCON trial – impact of 18F-fluciclovina PET/CT on clinical management choices for men with biochemically recurrente prostate cancer

• Local Treatment in Patients with Newly Diagnosed Metastatic Disease - Debates on Controversial Topics in Prostate Cancer (ARS)

Oligometastatic PC

1) UPFRONT

2) AT RECURRENCE

Oligometastatic prostate cancer is defined as up to five

extrapelvic lesions on conventional imaging.

Oligomets PC at RECURRENCE

Using Advanced PET Imaging to Detect Extrapelvic Disease in Patients with PSA Recurrences

Presented By Felix Feng at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

Presented By Eugene Teoh at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care Abs 165.Bottomley, oral presentation, ASCO GU 2018

The FALCON trial (NCT02578940)

Presented By Eugene Teoh at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

85 pts median PSA at recurrence 0.63 ng/ml

Abs 165.Bottomley, oral presentation, ASCO GU 2018

Oligomets PC UPFRONT: Both primary tumor and metastases can seed new mets

Which is the best treatment approach for oligometastatic disease ?

Presented By Felix Feng at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

Therapeutic Options

Presented By Elisabeth Heath at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

Oligo-recurrent/upfront PC Node and mets directed therapy

• Retrospective studies (2012-2017)

• Few patients (19 - 66 pts)

• Different oligometastatic diseases

• SRBT +/- ADT

• Different endpoints

LOCAL CONTROL AT 2 yrs 100%

Presented By Felix Feng at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

(modified)

Many Trials for Metastases-Directed Therapy

Presented By Felix Feng at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

LOCAL OPTIONS for Oligomets upfront PC Prostate directed therapy

HYPOTHESIS: A combination of primary tumor treatment, metastasis-directed therapy, and systemic therapy can potentially delay disease progression or in some cases be curative.

POTENTIAL BENEFITS OF RADICAL PROSTATECTOMY

• RP decreases:

– tumor burden

– disease-related morbidity

– need for palliative surgical intervention

• Increases time to development of CRPC

• improves PFS and cancer-specific survival (CSS) outcomes.

Ahmad, Oncology, nov 2017

LOCAL OPTIONS for Oligomets upfront PC Prostate directed therapy

Summary of Prostate-Directed Therapy

Presented By Felix Feng at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary

Care

RT + ADT

Presented By Elisabeth Heath at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

Presented at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care

Conclusions

• The definition of oligometastatic remains undefined

• Superior imaging is challenging the traditional paradigm based on conventional imaging.

• Such patients may be considered for aggressive approaches, including radical treatment of the primary cancer.

• Nonrandomized data suggest a survival benefit for patients who undergo treatment of the primary despite metastatic disease at diagnosis.

• Treatment of the primary in men with oligometastatic disease should be considered experimental.

• Clinical parameters

– Bone mets

– Visceral mets

• Disease parameters

– Gleason score

– Tumor burden low vs high

– M0 vs M1

CHAARTED High volume

Visceral mets and/or ≥ 4 bone mets (at last 1 beyond pelvis and vertebral column)

STAMPEDE ABI All

METASTATIC AT PRESENTATION

LATITUDE 2 or 3 HIGH RISK criteria Bone mets > 3 Gleason score > 8 Visceral mets

Oligometastatic PC upfront: population

To Sergio Bracarda

• The traditional approach to metastatic PC (systemic ADT) was challenged by the findings of the CHAARTED, STAMPEDE, and LATITUDE trials

• Considering results and OS obtained with ABI and DOCE in metastatic PC upfront setting, is the option to treat primary tumor reinforced?

• A more aggressive treatment?

cortega@aslcn2.it