Siwen Hu-Lieskovan, MD, PhD

DISCUSSANT OF the CheckMate 384 trial, Siwen Hu-Lieskovan, MD, PhD, Director of Solid Tumor Immunotherapy at the Huntsman Cancer Institute, University of Utah, called the short-term safety data “convincing.” However, she noted that the long-term impact of intermittent, lower-minimum concentration on efficacy, durability, and overall survival still remains to be determined.

“As Dr. Garon pointed out, the trial was designed to look for noninferiority, but because of the number enrolled, there is no statistical power to make a conclusion,” said Dr. Hu-Lieskovan. “Moreover, all enrolled patients have established benefit from the 240-mg-every-2 weeks regimen already, so this study is really addressing a maintenance durability of response issue rather than an action of the response. The follow-up is also short, with just 60% of patients reaching 12-month follow-up.”

In addition, she added, although the adverse-event profile is similar between the groups, it is not identical.

“Liver toxicity associated with the 480-mg dose is an impressive 0%, suggesting that a constant, moderate level of drug exposure may be more important than a peak level of exposure in the etiology of this toxicity,” she observed.

Questions Remain

ACCORDING TO Dr. Hu-Lieskovan, many questions remain to be answered, including whether full receptor occupancy or constant receptor occupancy is more important for maintaining response and whether the intermittent, lower-minimum concentration will affect the induction of response. Finally, she added, it’s unknown whether pharmacokinetic modeling and progression-free survival will correlate with overall survival. The translational study and the long-term follow-up from CheckMate 384 will help answer these questions, she concluded. ■

DISCLOSURE: Dr. Hu-Lieskovan disclosed relationships with Amgen, Bristol-Myers Squibb, Genentech/Roche, Genmab, Merck, Nektar, Neon Therapeutics, Pfizer, Plexxikon, and Vaccinex.