Nuovi target: sono sempre clinicamente utili?

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Nuovi target: sono sempre clinicamente utili?

Filippo Montemurro

Direzione Day Hospital Oncologico Multidisciplinare Istituto di Candiolo, FPO-IRCCS

Roma 25/05/2019

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Disclosures

Relationship Company/Organization

Advisory Role, Speaker’s Bureau, Travel Grants Roche Speaker’s Bureau, Compensation for editorial initiatives Novartis

Speaker’s Bureau Pfizer

Advisory role Lilly

Speaker’s Bureau, Compensation for editorial initiatives Astra Zeneca

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Molecular screening program to select molecular-based recommended therapies for metastatic cancer patients: analysis from the ProfiLER trial

Trédan et al, Ann Oncol pub 2019

HER2-amplified breast cancers, KIT/PDGFRA-driven cancers, ALK/ROS1/EGFR activating lung cancers or BRAF-mutated

melanoma, were included if they have already been treated with a specific MTA

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Study flow

Trédan et al, Ann Oncol pub 2019

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Activity Results

Initial number 275; potential target identified 138, treatment started 39, PR in 6 pts

ORR; 17%

ORR; 2%

0.9%

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Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study; group 3 (previously treated met. cancers)

Sicklick et al, Nature Med epub 2019 PLUS

• PD-L1 IHC

• TMB

• MSI

• Profiling of ctDNA by FoundationACT (62 genes)

MTB indications and:

• patient preference

• attention to comorbidities

• consideration of drug toxicities,

insurance payor coverage of off-label agent(s) investigational agent clinical trial availability

236-405 genes, mainly 315

Started February 2015

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Study flow

Median time from study consent to initiation 0.9 months

Median time from molecular results to initiation 2 months

Sicklick et al, Nature Med epub 2019

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Molecular alterations

Matching score>50

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Efficacy

_ORR _PFS2

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Treatments received by patients with high matching scores

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Genomic and transcriptomic profiling expands precision cancer medicine: the WINTHER trial

Rodon et al. Nature Medicine, epub 2019

236 genes

AND

Transcriptomic analysis Agilent Technologies Tumor and normal tissue

Comparative toxicogenomics database 2013-2015

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Patient flow

Rodon et al. Nature Medicine, epub 2019

Colon cancer; 32%

Head and neck; 21%

Lung cancer; 20%

66 pts received only 1 drug, 44 ≥1 drug

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Tumor response

Rodon et al. Nature Medicine, epub 2019 Study is negative

for the primary end-point

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Survival outcomes

ARM A ARM B ARM A/B

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Case Reports from WINTHER; exceptional responders

Lung Cancer T790M Afatinib and Cetuximab

Colorectal cancer, MSI Pembrolizumab

Well differentiated

Neuroendocrine Carcinoma, AKT2 and AKT3 overexpression Everolimus

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Pathways exploited clinically

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I nuovi marcatori; sono sempre clinicamente utili?

Al netto di tutti i potenziali caveat interpretativi,

l’approccio appare globalmente poco efficace e rimane investigational (?)