presentazione standard di powerpointplatelet count decreased 5 (10) 1 (2) 0 (0) 0 (0) phase iii is...

1 / 59 A. Cogoni – Colon-Retto

Innovazione e personalizzazione:

come i nuovi farmaci cambiano la strategia

terapeutica. GLI AGGIORNAMENTI

Colon Retto

Alessio Cogoni

UOC Oncologia


Median Survival Increases With Increased Lines of Therapy


Proportional Impact on Magnitude of OS Benefit Achieved Across Lines of Therapy


A classical case of mCRC in 2019


The Luxury of So Many Options: How Do 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.



Annals of Oncology, Volume 29, Issue 1, January 2018, Pages 44–70


Current Major Research Trends in 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



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 Se

con

d-l

ine

PFS

(%

)

Mos Patients at Risk, n 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



TRIBE-2 Trial



VISNU-1 Trial


VISNU-1 Trial

Sastre, et al. ASCO 2019


VOLFI Trial


Molecular Landscape in CRC

BRAF V600E (8-10%)


BEACON CRC Trial

Kopetz. NEJM. 2019


BEACON CRC Trial


BEACON CRC Trial

Kopetz. NEJM. 2019



MSI (4-5%)


Immunotherapy: Pembrolizumab

MK-3475-016


Immunotherapy: Nivolumab±Ipilimumab



Andre et al ASCO GI 2018 Overman et al JCO 2018



Lenz et al, ESMO 2018

1st line



Chalabi et al, ESMO 2018


Immunotherapy + Chemotherapy


Immunotherapy in MSS

CCTG CO.26

Chen et al, ASCO 2019



Chen et al, ASCO 2019



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



Ch

ange

fro

m b

asel

ine

(%) COLORECTAL CANCER

ORR (36%)

(33% with MSS pts)

MSI-H (all other patients were MSS) Time since first dosing (weeks)

Ch

ange

fro

m b

asel

ine

(%)

PD SD PR CR

Fukuoka et al, ASCO 2019



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



ImBlaze 370



HER2 (5 %)


HERACLES-A


MyPathway


MOUNTAINEER

Strickler et al, ESMO 2019


HERACLES-B


HERACLES-B

Sartore-Bianchi et al et al, ESMO 2019



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

STARTRK2 (ph II) + STARTRK1 (ph I) + ALKA-372-001 (ph I)


Conclusions

The treatment algorithm for mCRC have not changed in the last five years (apart from introduction of sidedness as a choice driver)

Continuum of care, the sequential exposure to all available treatments, is still the SOC

Chemotherapy triplets + biologics are gaining weight, but the best target population is unclear

Personalized medicine allows to tailor very small subgroups of patients who can benefit of target drugs with sometimes preliminary but outstanding evidences of activity


Grazie

[email protected]

presentazione standard di powerpointplatelet count decreased 5 (10) 1 (2) 0 (0) 0 (0) phase iii is...

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