Based on this result and similar findings within the validation cohort, the investigators concluded that patients with SRD or 6 months or longer should be designated as responders following cTACE. And, those with SRD of a period at least this long could allow patients in need of a liver transplant to remain on the donor list for an extended period of time, which could also contribute to improved survival in HCC.
The nearly 7-fold improvement in OS for those with SRD of 6 months or more is something remarkable, according to Jesse Berlin, ScD, who wrote an editorial accompanying the article by Dr Zhang and colleagues.2 “In more than 30 years as a statistician and epidemiologist, I have only very rarely seen HRs and [area under the receiver operating characteristic curve] of such a large magnitude.” Despite this fact, he noted it may still be too soon to begin using SRD as a surrogate end point. “We would have to see that a treatment effect on SRD at the trial level, which might be the HR comparing cTACE with some novel treatment, is reflected by a similar treatment effect on OS,” he wrote.
Dr Berlin also pointed out that the prognostic utility of SRD may not help physicians make actual clinical decisions about medications; rather, it just identifies patients with more indolent disease. The only way to know for sure if SRD could be a good surrogate end point, he concluded, would be by conducting a randomized clinical trial comparing a treatment algorithm based on SRD with treatment administered at regular intervals.
“An important caution is that this paper doesn’t show that SRD can be a surrogate for OS in HCC trials,” Bishal Gyawali, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts, wrote in a note to Cancer Therapy Advisor (Dr Gyawali was not involved in the study). “This study shows that SRD can be a good patient-level surrogate … However, this doesn’t prove that SRD can be a trial-level surrogate.”
Showing that the treatment effects on SRD translate into treatment effects on OS could make SRD a trial-level surrogate, added Dr Gyawali, echoing the sentiments of the editorial authored by Dr Berlin. “For that, we need a comparison of treatment outcomes versus the control for SRD and OS across trials.”
- Zhang Y, Zhang M, Chen M, et al. Association of sustained response duration with survival after conventional transarterial chemoembolization in patients with hepatocellular carcinoma. JAMA Netw Open. 2018;1(6):e183213.
- Berlin JA. Evaluating the potential benefits of using sustained response as a prognostic factor in intermediate hepatocellular carcinoma following treatment with conventional chemoembolization. JAMA Netw Open. 2018;1(6):e183209.