SAN FRANCISCO ― For patients with unresectable hepatocellular carcinoma (HCC), combining sorafenib (Nexavar, Bayer/Onyx) with transarterial chemoembolization (TACE) improved outcomes compared to the use of TACE alone.
Progression-free survival (PFS) was significantly longer for patients who received combination treatment as compared to those treated with TACE alone (25.2 months vs 13.5 months; hazard ratio [HR] = 0.59; P = .006).
These results come from the phase 2 open-label multicenter TACTICS study and were presented here at the Gastrointestinal Cancers Symposium (GICS) 2018.
This trial included a new endpoint, time to untreatable progression (TTUP) and/or progression to TACE refractoriness. For this endpoint, results also favored combination therapy (26.7 months vs 20.6 months; HR = 0.57; P = .02).
The results “clearly show that TACE in combination with sorafenib is a treatment option to improve clinical outcome and may be a standard of care in patients with intermediate-stage HCC,” commented lead author Masatoshi Kudo, MD, PhD, from the Department of Gastroenterology and Hepatology at Kindai University in Osaka-Sayama, Japan.
Longer Treatment Duration
For this trial, Dr Kudo and colleagues randomly assigned 156 patients with unresectable HCC to receive either TACE (n = 76) or sorafenib plus TACE (n = 80).
He noted that in this study, sorafenib was given for a longer period than in previous combination therapy trials.
In a previous studies, sorafenib had been given for 17 to 21 weeks, but subgroup analysis has suggested that a longer duration of treatment may improve clinical outcome.
Therefore, patients participating in the TACTICS trial received sorafenib for a median of 38.7 weeks.
Patients in the combination arm received sorafenib 400 mg once daily for 2 to 3 weeks prior to TACE. During TACE sessions, sorafenib 800 mg once daily was given. Treatment continued until TTUP, when TACE was no longer possible owing to untreatable tumor progression, deterioration to Child-Pugh class C, or the occurrence of vascular invasion and/or extrahepatic spread.
Dr Kudo added that new lesions were not regarded as indicative of progressive disease because such lesions are an aspect of natural tumor biology of HCC and do not imply treatment failure or the need to move to the next line of treatment.
In addition to significantly improving PFS and TTUP, adding sorafenib to TACE also significantly improved the median time to progression (24.1 months vs 13.5 months; HR = 0.56; P = .004 ).
Overall survival was not reached at the time of this analysis. Dr Kudo explained that these results will be presented at a future meeting, when the events reach the targeted numbers.
Adverse events were consistent with the known safety profile seen previously in TACE combination trials.
Confirmation Needed
In a discussion of the paper, Jordi Bruix, MD, head, Liver Unit, Barcelona Clinic Liver Cancer (BCLC) Group, the University of Barcelona, Spain, noted that in this study, adding adjuvant sorafenib to TACE proved to be safe and that it may provide benefit.
“The endpoint [TTUP] used in the trial is a good attempt to introduce something new that may be informative for the activity of combinations and adjuvant studies in the field of chemoembolization,” said Dr Bruix.
However, Dr Bruix noted that this novel endpoint requires validation and that it is important to see what the mature survival outcomes of the study ultimately reveal. He said that if those results show improved survival, then a confirmatory study with a large sample size should be conducted in the West.
The study was funded by the Japan Liver Oncology Group. Dr Kudo has participated in a consulting or advisory role with Kowa, MSD, Bristol-Myers Squibb, Bayer, Chugai Pharma, and Taiho Pharmaceutical; has received honoraria from Bayer, Eisai, MSD, and Ajinomoto; and has received research funding from Chugai Pharma, Otsuka, Takeda, Taiho Pharmaceutical, Sumitomo Dainippon, Daiichi Sankyo, MSD, Eisai, Bayer, and AbbVie. Dr Bruix has disclosed relationships with Argule, Bayer Schering, Bristol-Meyers Squibb, Kowa, Novartis, Onexo, Roche, BTG, and Sirtex Medical.
Gastrointestinal Cancers Symposium (GICS) 2018. Abstract 206, presented January 19, 2018.
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