5938 - Outcomes by prior transarterial chemoembolization (TACE) in the phase 3 CELESTIAL trial of cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC)

Background

Pts with HCC and localized disease commonly receive treatment with TACE but often progress and require systemic therapy. In the CELESTIAL trial (NCT01908426), C, an inhibitor of MET, VEGFR, and AXL, improved overall survival (OS) and progression-free survival (PFS) vs P in previously treated pts with advanced HCC. Median OS was 10.2 mo for C vs 8.0 mo for P (HR 0.76, 95% CI 0.63–0.92; p = 0.0049), and median PFS was 5.2 mo for C vs 1.9 mo for P (HR 0.44, 95% CI 0.36–0.52; p < 0.0001) (Abou-Alfa, JCO 2018). Here, outcomes were analyzed for pts who received prior TACE.

Methods

707 pts were randomized 2:1 to receive C (60 mg qd) or P stratified by disease etiology, geographic region, and extent of disease. Eligible pts had pathologic diagnosis of HCC, Child-Pugh score A, and ECOG PS ≤ 1. Pts must have received prior sorafenib and could have received up to two lines of prior systemic therapy for HCC. Outcomes were analyzed by number of prior TACE treatments (0, ≥1, 1-2, ≥3).Table: 704P

Results

Overall, 203 (43%) pts in the C arm and 111 (47%) pts in the P arm had received prior TACE with a median of 2 and 3 treatments, respectively. For pts who received TACE, 54% received 1-2 treatments and 46% received ≥3. 61% of pts enrolled in Asia, 39% in Europe, and 37% in North America received prior TACE. For pts who received prior TACE vs no TACE, 67% vs 76% received 1 prior systemic regimen and 32% vs 23% received 2. C was associated with improved OS and PFS vs P irrespective of prior TACE treatment (Table). Median OS was 11.4 mo for C vs 8.6 mo for P in pts with prior TACE and 9.5 mo for C vs 7.2 mo for P in pts with no prior TACE. Grade 3/4 adverse events were similar for pts with and without prior TACE in both arms.

Conclusions

C improved OS and PFS compared with P in pts with previously treated advanced HCC irrespective of whether they had received prior TACE.

Clinical trial identification

NCT01908426

Legal entity responsible for the study

The authors.

Funding

Exelixis, Inc.

Editorial Acknowledgement

Disclosure

A-L. Cheng: Honoraria, Consulting, Advisory role, Speakers\' bureau: Bayer, Eisai, Ono, Genentech, Novartis, BMS, Merck, MSD. T. Meyer: Consulting, Advisory role: Bayer, BTG, Ipsen; Research funding: Bayer, BTG. J-W. Park: Honararia: Bayer, BMS, Ono; Consulting, Advisory role: BMS, Ono, Bayer, Eisai, Midatech, Roche. H-J. Klümpen: Travel, accommodations and expenses to the ENETS knowledge network, sponsored by Ipsen. J. Knox: Honoraria: Novartis; Consulting or advisory role: Lilly, Merck; Research funding; AstraZeneca. M. Patel: Emplyee, Stock ownership: Exelixis, Genentech/Roche. A.B. El-Khoueiry: Honoraria: BMS, Bayer, Exelixis, EMD Serono, EISAI, Roche, Cytomx, Merck; Consulting or advisory role: BMS, Bayer; Research funding: AstraZeneca, Astex. R.K. Kelley: Consulting or advisory role: Genentech for IDMC (self), Bayer, BMS, AstraZeneca, DebioPharm, Agios; Research funding: Adaptimmune, Agios, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Exelixis, Eli Lilly, Medimmune, Merck, Novartis, Regeneron, Sanofi, Taiho, Target Pharma Solutions, Tekmira. G.K. Abou-Alfa: Self Consulting: Agios, Amgen, Antengene, Aptus, Aslan, Astellas, AstraZeneca, Bayer, BMS, Boston Scientifc, Carsgen, Celgene, Casi, Daiichi, Debio, Delcath, Eisai, Exelixis, Halozyme, Inovio, Ipsen, Merck, Onxeo, PCI Biotech, Roche, Sanofi, Servier, Sillajen, Sirtex, Yakult Immediate; Family member consulting: Celgene, CytomX, Gilead, Halozyme, Sanofi, Silenseed Institutional Research Agios, Array, AstraZeneca, Bayer, BMS, Casi, Celgene, Exelixis, Genentech, Incyte, Lilly, Mabvax, Medimmune, Momenta, Novartis, OncoMed Pharmaceuticals, Roche. All other authors have declared no conflicts of interest.