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Pembrolizumab monotherapy continued to demonstrate durable antitumor activity with promising overall survival in patients with advanced hepatocellular carcinoma who received prior treatment with sorafenib, according to updated data from cohort 1 of the phase 2 KEYNOTE-224 trial.
Pembrolizumab (Keytruda) monotherapy continued to demonstrate durable antitumor activity with promising overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC) who received prior treatment with sorafenib (Nexavar), according to updated data from cohort 1 of the phase 2 KEYNOTE-224 trial (NCT02702414).1
The findings presented at the 2022 ESMO World Congress on Gastrointestinal Cancer showed that patients in cohort 1 (n = 104) experienced a median OS of 13.2 months (95% CI, 9.7-15.3) at a median follow-up of 59.1 months. The 24- and 36-month OS rates were 30.8% and 20.2%, respectively.
Additionally, pembrolizumab produced a median progression-free survival (PFS) of 4.9 months (95% CI, 3.5-7.0) with 12- and 24-month PFS rates of 28.3% and 12.5%, respectively.
“This update of the KEYNOTE-224 study confirmed the efficacy of pembrolizumab in a subgroup of patients [pretreated with sorafenib] with really compelling long-term survival data and durable antitumor responses,” presenting study author Arndt Vogel, MD, a managing senior consultant and professor in the Department of Gastroenterology, Hepatology and Endocrinology, and head of the GI-Cancer Center at Hannover Medical School, said in an interview with OncLive®.
In November 2018, the FDA granted accelerated approval to pembrolizumab for the treatment of patients with HCC who have previously received sorafenib, based on prior findings from KEYNOTE-224.2 Previously reported data at a median follow-up of 12.3 months (interquartile range, 7.6-15.1) showed that pembrolizumab elicited a median OS of 12.9 months (95% CI, 9.7-15.5) with a 12-month OS rate was 54% (95% CI, 44%-63%). The median PFS was 4.9 months (95% CI, 3.4-7.2) with a 12-month PFS rate of 28% (95% CI, 19%-37%).3
KEYNOTE-224 enrolled adult patients who were at least 18 years old with pathologically confirmed HCC who experienced disease progression on or an intolerance to sorafenib. Patients were also required to be Child Pugh class A, have an ECOG performance status of 0 or 1, have BCLC stage C or B disease, and have a life expectancy of more than 3 months.
Enrolled patients were administered 200 mg of intravenous pembrolizumab every 3 weeks for up to 2 years, or until progressive disease, intolerable toxicity, withdrawal of consent, or investigator decision. Response was assessed every 9 weeks.
The primary end point of the trial was overall response rate (ORR) via central review per RECIST v1.1 criteria. Secondary end points included OS, PFS, duration of response (DOR) disease control rate (DCR), and safety and tolerability.
Additional data showed that pembrolizumab monotherapy generated an ORR of 18.3%, including a complete response rate of 3.8% and a partial response rate of 14.4%. Moreover, 43.3% of patients had stable disease, and 32.7% of patients had progressive disease. Notably, 1 patient was not evaluable, and 5 patients were not assessable. The DCR was 61.5%, and the median time to response was 2.1 months (range, 1.5-18.4). The median time to disease progression was 4.8 months (95% CI, 3.9-7.0).
Furthermore, patients who achieved a response at first imaging assessment, between days 40 and 77, experienced a greater OS benefit than patients who were non-responders at first assessment. Among responders at first assessment (n = 11), the median OS was 53.1 months (95% CI, 10.7–not reached) compared with 10.3 months (95% CI, 7.3-12.5) for non-responders at first assessment (n = 87).
The 24- and 36-month OS rates were 81.8% and 63.6%, respectively, for responders at first assessment, compared with 26.4% and 16.1%, respectively, for non-responders at first assessment.
Vogel and colleagues concluded that the updated results from KEYNOTE-224, plus results from the phase 3 KEYNOTE-394 trial (NCT03062358) and phase 3 KEYNOTE-240 trial (NCT02702401) and a meta-analysis of KEYNOTE-394 and KEYNOTE-240, support the broad applicability of pembrolizumab in the second-line treatment of advanced HCC.