personalizzazione:
come i nuovi farmaci cambiano la strategia
terapeutica.
GLI AGGIORNAMENTI
Colon Retto
Alessio Cogoni
UOC Oncologia
Lines of Therapy
Benefit Achieved Across Lines of Therapy
A classical case of mCRC in 2019
We Personalize Therapy?
la krisis, momento cruciale in cui il massimo disequilibrio del corpo
si trasforma nell’inizio della guarigione. La natura da sola non è capace,
però, di superare le fasi più critiche e le malattie più tenaci: diventa
indispensabile l’arte del medico.
We Personalize Therapy?
We Personalize Therapy?
Annals of Oncology, Volume 29, Issue 1, January 2018, Pages 44–70
Metastatic Colorectal Cancer
Intensification of therapy: the triplets
Individualization of therapy: new molecular predictive
factors and new drugs
Metastatic Colorectal Cancer
Intensification of therapy: the triplets
Individualization of therapy: new molecular predictive
factors and new drugs
TRIBE-2 Trial
Cremolini et al, ESMO GI / WCGIC 2019
TRIBE-2 Trial
Cremolini et al, ESMO GI / WCGIC 2019
TRIBE-2 Trial
Cremolini et al, ESMO GI / WCGIC 2019
TRIBE-2 Trial
Lower rates of per-protocol second-line treatment with FOLFOXIRI + bev → FOLFOXIRI + bev (59%) vs FOLFOX + bev → FOLFIRI + bev (78%)
Per-Protocol Second-line PFS
Second-line PFS (%)
Patients at Risk, n Mos FOLFOXIRI + bev FOLFIRI + bev
100 80 60 40 20
0
0 5 10 15 20 25
129 195
88 107
27 28
6 9
3 1
1 1
Cremolini et al, ESMO GI / WCGIC 2019
TRIBE-2 Trial
Cremolini et al, ESMO GI / WCGIC 2019
TRIBE-2 Trial
Cremolini et al, ESMO GI / WCGIC 2019
VISNU-1 Trial
VISNU-1 Trial
VISNU-1 Trial
Sastre, et al. ASCO 2019
VOLFI Trial
VOLFI Trial
Metastatic Colorectal Cancer
Intensification of therapy: the triplets
Individualization of therapy: new molecular predictive
factors and new drugs
Molecular Landscape in CRC
BRAF V600E (8-10%)
BEACON CRC Trial
Kopetz. NEJM. 2019
BEACON CRC Trial
Kopetz. NEJM. 2019
BEACON CRC Trial
Kopetz. NEJM. 2019
BEACON CRC Trial
Kopetz. NEJM. 2019
BEACON CRC Trial
BEACON CRC Trial
Kopetz. NEJM. 2019
BEACON CRC Trial
Kopetz. NEJM. 2019
Molecular Landscape in CRC
MSI (4-5%)
Immunotherapy: Pembrolizumab
MK-3475-016
Immunotherapy: Nivolumab±Ipilimumab
Immunotherapy: Nivolumab±Ipilimumab
Andre et al ASCO GI 2018 Overman et al JCO 2018
Immunotherapy: Nivolumab±Ipilimumab
Lenz et al, ESMO 2018
1st line
Immunotherapy: Nivolumab±Ipilimumab
Chalabi et al, ESMO 2018
Immunotherapy: Nivolumab±Ipilimumab
Chalabi et al, ESMO 2018
Immunotherapy + Chemotherapy
Immunotherapy + Chemotherapy
Immunotherapy in MSS
CCTG CO.26
Chen et al, ASCO 2019
Immunotherapy in MSS
Chen et al, ASCO 2019
Immunotherapy in MSS
Regorafenib Level 1: 80 mg/day
21 on 7 days off +
Nivolumab 3 mg/kg q2w
Regorafenib Level 2: 120 mg/day
21 on 7 days off +
Nivolumab 3 mg/kg q2w
Regorafenib Level 3: 160 mg/day
21 on 7 days off +
Nivolumab 3 mg/kg q2w Colorectal cancer Gastric cancer
Total 36 cases
N=3~6
N=3~6
N=3~6
DOSE ESCALATION COHORT:
3+3 design
EXPANSION COHORT
REGONIVO (EPOC 1603)
Fukuoka et al, ASCO 2019
Immunotherapy in MSS
Change from baseline (%) COLORECTAL CANCER ORR (36%) (33% with MSS pts)
MSI-H (all other patients were MSS)
Time since first dosing (weeks)
Change from baseline (%)
PD SD PR CR
Fukuoka et al, ASCO 2019
Immunotherapy in MSS
Adverse events, N (%) All
n=50
Regorafenib 80 mg n=22
All grades Grade≥3 All grades Grade≥3
All events 50 (100) 20 (40) 22 (100) 6 (27)
Palmar-plantar erythrodysesthesia 35 (70) 5 (10) 13 (59) 0 (0)
Hypertension 24 (48) 2 (4) 10 (46) 2 (9)
Fatigue 23 (46) 0 (0) 10 (46) 0 (0)
Rash 21 (42) 6 (12) 8 (36) 0 (0)
Fever 20 (40) 0 (0) 8 (36) 0 (0)
Proteinuria 15 (30) 6 (12) 5 (23) 2 (9)
Liver dysfunction 14 (28) 3 (6) 5 (23) 2 (9)
Oral mucositis 11 (22) 0 (0) 3 (14) 0 (0)
Diarrhea 11 (22) 1 (2) 5 (23) 0 (0)
Decreased appetite 11 (22) 0 (0) 6 (27) 0 (0)
Hyperthyroidism 6 (12) 0 (0) 4 (18) 0 (0)
Hypothyroidism 6 (12) 0 (0) 4 (18) 0 (0)
Hoarseness 5 (10) 0 (0) 4 (18) 0 (0)
Platelet count decreased 5 (10) 1 (2) 0 (0) 0 (0)
Phase III is about to start!!!
Fukuoka et al, ASCO 2019
Immunotherapy in MSS
ImBlaze 370
Immunotherapy in MSS
Molecular Landscape in CRC
HER2 (5 %)
HERACLES-A
MyPathway
MOUNTAINEER
Strickler et al, ESMO 2019
HERACLES-B
HERACLES-B
Sartore-Bianchi et al et al, ESMO 2019
Molecular Landscape in CRC
NTRK (0,5-1%)
TRK Fusion Inhibitors
Larotrectinib
Lassen U et al, ESMO 2018
Adult Trial (ph I) + NAVIGATE (ph II) + SCOUT (ph I/II Pediat)
Entrectinib
Demetri et al, ESMO 2018