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

FUGA-BT – Study Design

Morizane C et al. ASCO GI 2018; abstr 205

354 pts

179 pts

175 pts

Baseline Characteristics

Morizane C et al. ASCO GI 2018; abstr 205

OS, PFS, and ORR

Morizane C et al. ASCO GI 2018; abstr 205

Clinically Significant AEs

Morizane C et al. ASCO GI 2018; abstr 205

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

Safety

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

Primary Endpoint: PFS

Yoon SM et al. ASCO GI 2018; abstr 210

TTP, OS, and Outcomes at 24 weeks

Yoon SM et al. ASCO GI 2018; abstr 210

Safety and Conclusions

TACE + RT vs sorafenib • Well-tolerated • Improved PFS, ORR, TTP, OS

Yoon SM et al. ASCO GI 2018; abstr 210

KEYNOTE-224 – Study Design

Zhu AX et al. ASCO GI 2018; abstr 209

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

PFS and OS

Zhu AX et al. ASCO GI 2018; abstr 209

Safety

Zhu AX et al. ASCO GI 2018; abstr 209

Conclusions

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

Baseline Characteristics

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

OS and PFS in Subgroups

Abou-Alfa GK et al. ASCO GI 2018; abstr 207

OS and PFS – Sorafenib as only prior Tx

Abou-Alfa GK et al. ASCO GI 2018; abstr 207

Safety

Abou-Alfa GK et al. ASCO GI

2018; abstr 207

Conclusions

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

A cura di

Thank you!

Liver and Biliary Tract Cancers - Highlights