Liver and Biliary Tract Cancers Highlights

Transcription

1 Liver and Biliary Tract Cancers Highlights A cura di Lorenza Rimassa, MD Medical Oncology Unit, Humanitas Research Hospital IRCCS, Rozzano (Milano)

2 Disclosures Consulting or Advisory Role: Lilly, Bayer, Sirtex Medical, Italfarmaco, Sanofi, ArQule, Baxter, Ipsen, Exelixis Honoraria: AstraZeneca, AbbVie Travel Expenses: ArQule, Ipsen 175 pts 179 pts

3 Outline Biliary Tract Cancers FUGA-BT: Phase 3 trial of GEM+S1 vs GEM+CDDP HCC Locoregional and systemic therapy TACTICS: Phase 2 trial of TACE+sorafenib vs TACE START: Phase 2 trial of TACE+RT vs sorafenib in pts with MVI HCC Systemic therapy KEYNOTE-224: Pembrolizumab second-line phase 2 trial CELESTIAL: Cabozantinib second/third-line phase 3 trial

4 FUGA-BT Study Design 354 pts 175 pts 179 pts Morizane C et al. ASCO GI 2018; abstr 205

5 Baseline Characteristics Morizane C et al. ASCO GI 2018; abstr 205

6 OS, PFS, and ORR Morizane C et al. ASCO GI 2018; abstr 205

7 Clinically Significant AEs Morizane C et al. ASCO GI 2018; abstr 205

8 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

9 TACTICS - Study Design Stratification factors: Center, Milan criteria (yes vs no), number of prior TACE (0 vs 1-2) 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 Kudo M et al. ASCO GI 2018; abstr 206

10 Primary Endpoint: PFS OS (co-primary endpoint): data not mature Kudo M et al. ASCO GI 2018; abstr 206

11 Secondary Endpoints: TTUP and TTP TTUP: Time to UnTACEable Progression Kudo M et al. ASCO GI 2018; abstr 206

12 Safety Kudo M et al. ASCO GI 2018; abstr 206

13 Conclusions 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 Kudo M et al. ASCO GI 2018; abstr 206

14 START Baseline Characteristics Eligibility criteria: First diagnosis of HCC with major VI and no EHS Yoon SM et al. ASCO GI 2018; abstr 210

15 Primary Endpoint: PFS Yoon SM et al. ASCO GI 2018; abstr 210

16 TTP, OS, and Outcomes at 24 weeks Yoon SM et al. ASCO GI 2018; abstr 210

17 Safety and Conclusions TACE + RT vs sorafenib Well-tolerated Improved PFS, ORR, TTP, OS Yoon SM et al. ASCO GI 2018; abstr 210

18 KEYNOTE-224 Study Design Zhu AX et al. ASCO GI 2018; abstr 209

19 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

20 PFS and OS Zhu AX et al. ASCO GI 2018; abstr 209

21 Safety Zhu AX et al. ASCO GI 2018; abstr 209

22 Conclusions Zhu AX et al. ASCO GI 2018; abstr 209

23 CELESTIAL - Study Design 773 pts enrolled from Sep 2013 to Sep 2017 Abou-Alfa GK et al. ASCO GI 2018; abstr 207

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

25 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= SD 60% vs 33% Abou-Alfa GK et al. ASCO GI 2018; abstr 207

26 OS and PFS in Subgroups Abou-Alfa GK et al. ASCO GI 2018; abstr 207

27 OS and PFS Sorafenib as only prior Tx Abou-Alfa GK et al. ASCO GI 2018; abstr 207

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

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

30 Take-Home Messages Five Positive Trials Biliary Tract Cancers FUGA-BT: New standard of care? Probably in Japan HCC Locoregional and systemic therapy TACTICS and START: Interesting and promising results, Japanese and Korean studies, more data needed HCC Systemic therapy KEYNOTE-224: Confirmed IO data, waiting for phase 3 CELESTIAL: New standard of care, third-line therapy, sorafenib-intolerant patients, more data expected

31 Liver and Biliary Tract Cancers - Highlights A cura di Thank you!