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A cura di
Lorenza Rimassa, MD Medical Oncology Unit, Humanitas Research Hospital – IRCCS,
Rozzano (Milano)
Liver and Biliary Tract Cancers Highlights
Disclosures
179 pts
175 pts
Consulting or Advisory Role:
•Lilly, Bayer, Sirtex Medical, Italfarmaco, Sanofi, ArQule, Baxter, Ipsen, Exelixis
Honoraria:
•AstraZeneca, AbbVie
Travel Expenses:
•ArQule, Ipsen
Outline
CELESTIAL: Cabozantinib second/third-line phase 3 trial
KEYNOTE-224: Pembrolizumab second-line phase 2 trial
TACTICS: Phase 2 trial of TACE+sorafenib vs TACE
START: Phase 2 trial of TACE+RT vs sorafenib in pts with MVI
FUGA-BT: Phase 3 trial of GEM+S1 vs GEM+CDDP
HCC – Systemic therapy
HCC – Locoregional and systemic therapy
Biliary Tract Cancers
Conclusions
GS demonstrated non-inferiority to GC in OS with good tolerability and was considered as new convenient option of standard of care
Morizane C et al. ASCO GI 2018; abstr 205
TACTICS - Study Design
Stratification factors: Center, Milan criteria (yes vs no), number of prior TACE (0 vs 1-2)
Kudo M et al. ASCO GI 2018; abstr 206
• This trial used a new endpoint: time to untreatable (unTACEable) progression and/or progression to TACE refractoriness
• New intrahepatic lesions not regarded as progressive disease
Primary Endpoint: PFS
OS (co-primary endpoint): data not mature
Kudo M et al. ASCO GI 2018; abstr 206
Secondary Endpoints: TTUP and TTP
TTUP: Time to UnTACEable Progression
Kudo M et al. ASCO GI 2018; abstr 206
Conclusions
Kudo M et al. ASCO GI 2018; abstr 206
• TACE in combination with sorafenib
• significantly improved PFS compared to TACE alone
• is feasible and safe
• Longer sorafenib treatment duration (38.7 wks) may be the key of success of this trial compared to failed trials (e.g., SPACE 21 wks)
• New intrahepatic lesions should not be regarded as PD/stopping rule
• TACE in combination with sorafenib is a treatment option to improve outcome and may be a standard of care in pts with intermediate HCC
START – Baseline Characteristics
Yoon SM et al. ASCO GI 2018; abstr 210
Eligibility criteria: First diagnosis of HCC with major VI and no EHS
Safety and Conclusions
TACE + RT vs sorafenib • Well-tolerated • Improved PFS, ORR, TTP, OS
Yoon SM et al. ASCO GI 2018; abstr 210
ORR
• Median time to response: 2.1 mos (range 1.8 to 4.8) • Duration of response >6 mos: 94% • Median DOR: 8.2 mos (range 2.3+ to 8.3+)
Zhu AX et al. ASCO GI 2018; abstr 209
CELESTIAL - Study Design
773 pts enrolled from Sep 2013 to Sep 2017
Abou-Alfa GK et al. ASCO GI 2018; abstr 207
OS, PFS, and ORR
Second interim analysis • 707 randomized pts • 78% (484) of required events • Primary endpoint (p=0.0049)
met the critical p-value <0.021
ORR 4% vs 0.4%, p=0.0086 SD 60% vs 33%
Abou-Alfa GK et al. ASCO GI
2018; abstr 207
Take-Home Messages – Five Positive Trials
CELESTIAL: New standard of care, third-line therapy, sorafenib-intolerant patients, more data expected
KEYNOTE-224: Confirmed IO data, waiting for phase 3
TACTICS and START: Interesting and promising results, Japanese and Korean studies, more data needed
FUGA-BT: New standard of care? Probably in Japan
HCC – Systemic therapy
HCC – Locoregional and systemic therapy
Biliary Tract Cancers