Author: By Hannah Kitt, medwireNews Reporter
medwireNews: Pembrolizumab may prolong overall survival (OS) in patients from Asia with previously treated advanced hepatocellular carcinoma (HCC), phase III study results suggest.
Speaking at the 2022 ASCO Gastrointestinal Cancers Symposium in San Francisco, California, USA, study author Shukui Qin, from Nanjing Chinese Medicine University, explained that HCC is “[f]requently diagnosed at advanced stages not amenable to curative treatment approaches.”
He added that “[a]lthough globally approved anti-angiogenic therapy has improved clinical outcomes in the second-line treatment setting, available treatment options benefit a minority of patients”, and “[t]here is a high unmet medical need for therapies that prolong survival and are tolerable.”
The researchers therefore investigated pembrolizumab, which has previously shown efficacy and manageable toxicity in global phase II and III trials in the Asian setting of advanced HCC.
The KEYNOTE-394 study included 453 patients with advanced HCC who had previously received sorafenib or oxaliplatin-based chemotherapy. In total, 300 patients were randomly assigned to receive pembrolizumab 200 mg every 3 weeks for a maximum of 35 cycles while the remaining 153 participants were given placebo on the same schedule; all patients also received best supportive care.
After a median follow-up of 33.8 months, patients who were given pembrolizumab had a significantly longer median OS than those given placebo, at 14.6 versus 13.0 months. This equated to a hazard ratio (HR) for death of 0.79 in favour of the PD-1 inhibitor.
A similar trend was observed for the other outcomes investigated. Indeed, the median progression-free survival was 2.6 months with pembrolizumab versus 2.3 months with placebo, a significant difference giving an HR for progression or death of 0.74.
The objective response rate (ORR) was also significantly higher with pembrolizumab than placebo, at 12.7% and 1.3%, respectively, and the median duration of response was longer with pembrolizumab, at 23.9 versus 5.6 months.
Reporting on the safety, Qin said that the adverse event (AE) profile of the PD-1 inhibitor “was manageable and consistent with previous reports in this patient population.”
Treatment-related (TR)AEs of grade 3–5 occurred in 14.4% of pembrolizumab-treated patients and 5.9% of those given placebo; the respective rates of immune-mediated AEs of grade 3–5 were 3.0% and 0.0%.
A total of 4.0% of patients in the pembrolizumab group discontinued treatment due to a TRAE, as did 0.7% of those in the placebo group. Three deaths in the pembrolizumab arm were attributed to TRAEs compared with none in the placebo arm.
“These data reinforce the benefit-risk balance for pembrolizumab observed in globally conducted studies in the second-line treatment of advanced HCC and provide support for the generalizability of the date worldwide”, concluded Qin.
Qin S, Chen Z, Fang W, et al. Pembrolizumab plus best supportive care versus placebo plus best supportive care as second-line therapy in patients in Asia with advanced hepatocellular carcinoma (HCC): Phase 3 KEYNOTE-394 study. J Clin Oncol 2022;40(4_suppl):383–383. DOI: 10.1200/JCO.2022.40.4_suppl.383
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