Ongoing projects and perspectives for collaborations
Università di Verona AOUI Verona
• Expanding molecular profiling and
implementing a Precision Medicine approach
• Global Integrated Care
Molecular Tumor Board-based
implementation of Precision Oncology
AIRG IG 2019 submitted Milella & Scarpa co-PIs
The ICGC-ARGO italian chapter:
Profiling OrphaN Tumors for
trEatment selection - PONTE
Implementing Precision Medicine in clinical practice remains challenging, as clinical trials have failed so far to demonstrate OS advantages in unselected patients'
populations.
We have therefore elected to profile orphan tumors, defined as rare cancers for which orphan-drug status might apply, including: classical rare cancers, rare histologies of common cancers, malignancies that currently have no defined
molecular diagnostic paths, thereby excluding common cancers for which a standard molecular profiling is indicated (see national AIOM-SIAPEC guidelines for reference);
however, common cancers testing negative for standard molecular biomarkers (e.g.
EGFR/KRAS/ALK/ROS1-negative NSCLC) could be considered for profiling within this project upon Molecular Tumor Board discussion and recommendation.
Drug access for driver/matched therapy will be prioritized as follows: clinical trials available at the proponent and/or collaborating Institutions, ad hoc designed clinical trials (including clinical trials designed for recurrent - i.e. encountered in >2% of the retrospective dataset - potentially driver aberrations, see below), off label drug use.
We aim at demonstrating a prevalence of potentially actionable drivers in at least
30% of the orphan tumors patient population (as defined above). To this purpose, we
plan to retrospectively profile 800 cases (which will also be used to define recurrent
drivers, see above) and prospectively profile 1200 cases. Clinical data will be collected
for both the retrospective and prospective populations (see below).
The FoundationOne Lung-Seq Program
• FOne profiling free of charge for a predefined number of pts
• NSCLC in first-line treatment
• Standard molecular profiling performed at sites
L'idea di condividere una strategia di "selezione" nasce dalla considerazione che un approccio di profilazione "broad-based" in popolazioni non selezionate ha già
mostrato i suoi limiti (in sostanza l'assenza di un vantaggio in termini di outcome di popolazione) nei confronti di una profilazione ristretta alle 3 o 4 alterazioni con implicazioni terapeutiche che sono già uno standard.
A Verona testeremo quindi con FoundationOne pazienti "quadrupli negativi".
Se siete d'accordo condivideremo la seguente strategia di "selezione» e i dati che ne deriveranno:
• NSCLC (senza distinzione di istologia)
• Stadio clinico IIIB (non candidato a trattamento loco-regionale/immuno a mantenimento)/IIIC/IV
• EGFR/KRAS/ALK/ROS1 negativi (se possibile), oppure
• EGFR/ALK/ROS1 negativi (se KRAS non è fattibile d'ambleè)
Cabozantinib 1L
Medical treatment of mRCC: an ever evolving timeline…
Sorafenib Pazopanib Axitinib
Sunitinib
Lenvatinib (+ everolimus) Cabozantinib Temsirolimus
Bevacizumab (+ IFN-α)
Nivolumab Everolimus
Tivozanib
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018
IFN, interferon.
2019?
2019?
Ipilimumab + nivolumab
Axitinib + pembrolizumab
Axitinib + avelumab Atezolizumab
+ bevacizumab
Stato dell’arte in I-L: la mia (personale)
visione…
…troppo facile?
Angio-addict Immunogenic
Good Intermediate Poor
1. Motzer RJ, et al. J Clin Oncol 1993;11:1368-75; 2. Heng DY, et al. Lancet Oncol 2013;14:141-8.
Immunotherapy era1 Targeted agents era2
Median OS of good risk patients 20 months 43.2 months (95% CI: 31.4–50.1) Median OS of intermediate risk patients 10 months 22.5 months (95% CI: 18.7–25.1) Median OS of poor risk patients 4 months 7.8 months (95% CI: 6.5–9.7)
Ma le classi di rischio sono PROGNOSTICHE... Non PREDITTIVE!!!
Good Intermediate Poor
Other clinico-pathological features (i.e. sarcomatoid component)???
PD-L1 expression
…troppo facile?
Angio-addict Immunogenic
Other clinico-pathological features (i.e. sarcomatoid component)???
PD-L1 expression
Angiogenesis signature T- cell effector signature
…troppo facile?
Good Intermediate Poor
Angio-addict Immunogenic
Other clinico-pathological features (i.e. sarcomatoid component)???
PD-L1 expression
…troppo facile?
Good Intermediate Poor
Angio-addict Immunogenic
Angiogenesis signature T- cell effector signature
Ongoing projects and perspectives for collaborations
Università di Verona AOUI Verona
• Expanding molecular profiling and
implementing a Precision Medicine approach
• Global Integrated Care
Focus On Research and CarE (FORCE)
Approccio di Presa in Carico Globale Integrata Evidence-based nel Paziente Oncologico
Oncologia Medica, Dipartimento di Medicina, Università di Verona,
Azienda Ospedaliera Universitaria Integrata, Verona
Medico oncologo (dott. Sara Pilotto)
- Presa in carico - Coordinatore
Psicologa in ambito oncologico
(dott. Daniela Tregnago) - Supporto psicologico
individuale
Chinesiologa
(dott. Alice Avancini) - Esercizio fisico
adattato Dietista Nutrizionista
(dott. Ilaria Trestini) - Screening e valutazione
nutrizionale
- Counseling nutrizionale
Un Team che si Prenda Cura della Persona…
… con un Approccio Personalizzato
… con un Approccio SCIENTIFICO Rigoroso ed Evidence-based
Produrre nuove evidenze scientificamente valide in grado
di implementare la conoscenza Garantire al paziente il
miglior percorso terapeutico possibile
Fornire un modello di cura applicabile in modo trasversale al
contesto oncologico, ma anche generalizzabile alla cura in patologie
croniche complesse
Muscle derangement and alteration of the nutritional machinery in NSCLC.
Trestini I, Gkountakos A, Carbognin L, Avancini A, Lanza M, Molfino A, Friso S, Corbo V, Tortora G, Scarpa A, Milella M, Pilotto S.
Submitted to Critical Reviews in Oncology / Hematology
Identifying factors which contribute to a worsening nutritional status and understanding the role of genetic polymorphisms may facilitate the development of a tailored intervention
in order to provide optimal care and improve clinical outcomes in NSCLC pts.
Unpublished data
Prevalence of clinical and sub-clinical malnutrition in advanced non-small- cell lung cancer patients and association with outcome.
Trestini I, Sperduti I, Sposito M, Kadrija D, Drudi A, Tregnago D, Pio Di Noia V, Gkountakos A, D'Argento E, Carbognin L, Santo A, D'onofrio M, Tortora G, Bria E, Milella M, Pilotto S.
Objectives
• The present study aimed to explore prevalence of malnutrition and its correlation with outcome in A-NSCLC pts.
Results
• NRS was a significant independent predictor for PFS (p = 0.01).
• Pts with baseline NRS≤3 had significantly longer 1-year PFS (58.6% vs
16.7%, p = 0.04) and 2-year OS (90.6% vs 68.3%, p = 0.03) and a better ORR than those with NRS > 3 (66.7% vs 21.4%).
• In pts treated with immunotherapy, loss in muscle mass (p = 0.01) correlated with worse ORR, PFS and OS, although differences did not reach a statistical significance.
Conclusion
• Malnutrition has a detrimental impact on ORR, PFS and OS in A-NSCLC, including pts treated with immunotherapy.
Prognostic impact of early nutritional support in patients affected by locally advanced and metastatic pancreatic ductal adenocarcinoma undergoing chemotherapy.
VOLUME 72 • NUMBER 5 • MAY 2018 CLINICAL REPORT
Trestini I, et al. Eur J Clin Nutr. 2018
Protein, malnutrition and wasting disorders
The time between the diagnosis of PDAC and the nutritional support was an
independent predictor of OS.
Trestini I, Carbognin L, Sperduti I, Bonaiuto C, Auriemma A, Melisi D, Salvatore L, Bria E, Tortora G.
Abstract/poster presentati a congressi nazionali ed internazionali:
The nutritional intervention was an independent predictor for better OS.
Tailored nutritional intervention as a predictive factor for survival outcomes in patients affected by Head and Neck Cancer undergoing chemotherapy
and/or radiotherapy.
Unpublished data
Trestini I, Carbognin L, Sperduti I, Bonaiuto C, Tondulli L, Pilotto S, Tortora G, Milella M, Bria E.
Progetti ongoing – Il Supporto Psicologico
• Progetto di umanizzazione delle cure: Assistenza psicologica in ambito oncologico
• Rilevazione dei sintomi ansiosi, depressivi e del distress emotivo nel pazienti oncologici
• Promuovere il benessere psicologico nei pazienti oncologici attraverso l’applicazione del protocollo relativo alla
psicoterapia breve per il benessere psicologico
S.T.I.P.-ON. (Sostenibile Training In Pazienti Oncologici)
L’esercizio fisico
C.H.O.iC.E. (Choose Health: Oncological patients Centered Exercise)
• Trial randomizzato multicentrico, che valuti l’efficacia preliminare, di un programma di esercizio fisico, basato sulle attuali linee guida, ma tenga in considerazione le preferenze delle persone.
M.O.T.O (Motives, Obstacles Towards run in Oncology)
• Analisi qualitativa delle motivazioni e delle barriere nell’attività podistica, nel contesto dell’iniziaiva «Run for Science».
E.D.u.C.A. (Educational materials Development for physical activity in CAncer patients)
E.C.H.O. (Exercise in Cancer: the Healthcare professionals Opinion)
• Validazione di una guida informativa e pratica sull’attività fisica nei pazienti con diagnosi oncologica.
• Identificare l’opinione degli operatori sanitari verso la raccomandazione della pratica di esercizio fisico nel contesto oncologico;
• Identificare le conoscenze, le barriere e le motivazioni riguardo la promozione dell’esercizio fisico.
Progetti ongoing – L’esercizio fisico adattato
Impact of a comprehensive lifestyle
intervention on immunological parameters and outcome in non-small-cell lung cancer
Hypothesis: A comprehensive lifestyle intervention including:
1) nutritional management 2) physical activity and 3) psychological support
may modulate immunological parameters and improve
immunotherapy outcome in
NSCLC patients.
Impact of a comprehensive lifestyle
intervention on immunological parameters and outcome in non-small-cell lung cancer
Task: aims to build a signature for predicting the outcome of
immunotherapy-treated NSCLC patients
Tissue-based Blood-based
RETROSPECTIVE & PROSPECTIVE PHASE
Task: aims to evaluate the effect of our comprehensive lifestyle approach on the
outcome of immunotherapy-treated NSCLC patients
Nutritional status Muscle wasting
Physical activity level
Psychological state
