AIOM Giovani 2018 Perugia, 06-07 Luglio 2018
Regione del Veneto
Vincenzo Dadduzio UOC Oncologia Medica 1
Dipartimento di Oncologia Clinica e Sperimentale Istituto Oncologico Veneto – IRCCS, Padova
EPATOCARCINOMA
Nuovi Trattamenti all’Orizzonte?
The Story So Far…2007
• Sorafenib better than placebo in two phase III trials
• First drug ever approved for advanced HCC
mOS: 10.7 vs 7.9 months HR 0.69
mOS: 6.5 vs 4.2 months HR 0.68
Llovet J, NEJM 2007 Cheng AL, Lancet Oncol 2009
Forner A, Lancet 2012
New Treatments on the H(CC)orizon?
Adapted from Forner A, Lancet 2018
In early 2017, if you asked me….
I had to give one answer
Forner A, Lancet 2018
2017: A New Era Begins
Bruix J, Lancet 2017
2017: A New Era Begins
Bruix J, Lancet 2017
mOS 10.6 vs 7.8 months (HR 0.63) mPFS 3.1 vs 1.5 months (HR 0.46)
Slide 13
7
from Cheng AL, ASCO GI 2018
5 2
New Treatment on the Horizon: SPOILER ALERT!
2017-2018: New TKI(d)s on the Block
ASCO 2017:
- Lenvatinib non-inferior vs sorafenib in 1° Line (ph III) ASCO GI 2018:
- Cabozantinib superior to placebo in 2°/3° Line (ph III) ASCO 2018
- Ramucirumab superior to placebo in aFP >400 ng/ml, 2° Line, (ph III)
Lencioni R, presented at ASCO GI 2018
from Abou-Alfa GK, ASCO GI 2018
from Abou-Alfa GK, ASCO GI 2018
from Abou-Alfa GK, ASCO GI 2018
from Abou-Alfa GK, ASCO GI 2018
from Zhu A, ASCO 2018
from Zhu A, ASCO 2018
from Zhu A, ASCO 2018
from Zhu A, ASCO 2018
LENVATINIB (1° Line):
Pro: better PFS and ORR performance, less HFSR than sorafenib Con: higher hypertension, no 2°/3° line strategies available
CABOZANTINIB (2°/3° Line):
Pro: 28% pts treated in 3° Line
Con: marginal OS gain in 3° Line (HR 0,90)
REGORAFENIB (2° Line):
Pro: First 2° Line study to show OS and PFS advantage vs placebo Con: only for 2° Line, Sorafenib tolerant patients (at least 400 mg)
RAMUCIRUMAB (2° Line):
Pro: 1° positive study with biomarker selection Con: marginal OS delta in REACH2 (+1.2 months)
New TKI(d)s on the Block: RECAP
HCC 2018: the Anti-angiogenic Renaissance
1° LINE 2° LINE 3° LINE
Sorafenib Regorafenib Cabozantinib
Sorafenib Cabozantinib ???
Sorafenib Ramucirumab* Cabozantinib
Lenvatinib ??? ???
* In patients with aFP >400 ng/mL
New Players on the Field: the Immuno Approach
Nivolumab ph I/II: Dose Expansion Data (1°/2° L)
adapted from El-Khoueiry A, Lancet 2017
Sorafenib exposed patients: n=145 [68%]
Nivolumab ph I/II: Dose Expansion Data (1°/2° L)
Pembrolizumab phase II (2° L) – KEYNOTE 224
Pembrolizumab phase II (2° L)
adapted from Zhu A, Lancet Oncol 2018
Pembrolizumab phase II (2° L)
adapted from Zhu A, Lancet Oncol 2018
10 Jan 2017
11 Jun 2018
Immunotherapy in HCC: ready to next steps?
• 2°L data to be confirmed in phase III RCT: Pembro vs BSC ongoing
(NCT02702401– data expected in early 2019)
• 1°L phase III ongoing with Nivolumab vs Sorafenib
(NCT02576509 – data expected in late 2019)
• Early-phase trials with combination strategies ongoing
- Anti-PD1 + AntiCTLA4 + TKIs (phase II) - Anti-PD1 + Anti-VEGF (phase III)
- Anti-PD1 + TACE (phase I)
• Anti-PD1 in adjuvant setting after resection/ablation (phase III)
HCC 2019: Anti-angio + Immuno Approach ?
1° LINE 2° LINE 3° LINE
Sorafenib Rego/Cabo/Ramu Nivo / Pembro Sorafenib Nivo / Pembro Cabozantinib
Lenvatinib Nivo / Pembro ???
Nivo / Pembro Sorafenib Rego/Cabo/Ramu
vincenzo.dadduzio@iov.veneto.it
