Home Gastrointestinal Pembrolizumab shows promising OS for previously untreated advanced HCC

Pembrolizumab shows promising OS for previously untreated advanced HCC


January 19, 2021

3 min read



Van Laethem J-L, et al. Abstract 297. Presented at: Gastrointestinal Cancers Symposium (virtual meeting); Jan 15-17, 2021.

Van Laethem reports no relevant financial disclosures. Please see the abstract for all other researchers’ relevant financial disclosures.

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First-line pembrolizumab induced durable antitumor activity and promising OS among patients with advanced hepatocellular carcinoma, according to data from the phase 2 KEYNOTE-224 study presented at Gastrointestinal Cancers Symposium.

Immunotherapy as monotherapy can offer “excellent benefit” for around 25% to 30% of patients in this setting, or it can be used in combinations to provide new treatment options for patients with hepatocellular carcinoma, according to Jean-Luc Van Laethem, MD, PhD, of the department of gastroenterology and digestive oncology at Hôpital Erasme – Université Libre de Bruxelles in Belgium.

“Immunotherapy can offer a good [complement] beside antiangiogenics or associated treatments,” he told Healio. “Chemotherapy is poorly active in HCC, and there are contradictions for angiogenic therapy, like variceal bleeding or varices.”

Previously reported data from cohort 1 of KEYNOTE-224, a single-arm, multi-country trial, showed pembrolizumab (Keytruda, Merck) was effective and safe among patients with advanced HCC who had previously received sorafenib (Nexavar, Bayer).

Jean-Luc Van Laethem, MD, PhD

Jean-Luc Van Laethem

In the current analysis, Van Laethem and colleagues evaluated data of 51 patients (median age, 68 years; range, 41-91; 86% men) enrolled in cohort 2 of the trial who received 200 mg IV pembrolizumab every 3 weeks for 2 years as first-line therapy. All patients had incurable HCC not amenable or refractory to locoregional therapy, Child-Pugh class A liver disease, ECOG performance status of 0 or 1 and Barcelona Clinic Liver Cancer stage C (67%) or B (33%) disease. Alcohol use was a predisposing factor for HCC in 47% of cases, 18% of patients had vascular invasion and 35% had extrahepatic disease.

The rationale for studying pembrolizumab, an anti-PD-1 agent, in this population is that these are “heterogeneous tumors, and a part are inflammatory (mainly hepatitis C virus or hepatitis B virus derived), with overexpression of PD-L1,” Van Laethem said.

Overall response rate served as the study’s primary endpoint. Secondary endpoints included duration of response, disease control rate, time to progression, PFS and OS.

Median time from first dose to data cutoff was 21 months (range, 17-23).

Researchers reported an ORR of 16% (95% CI, 7-29), all of which were partial responses, and ORR appeared similar across patient subgroups. Forty-one percent of patients achieved stable disease, for a disease control rate of 57%.

Median duration of response was not reached (range, 3-20+ months), although researchers estimated 70% of responses lasted for at least 12 months.

Median time to progression was 4 months (95% CI, 3-8).

Twenty-four percent of patients achieved 12-month PFS, and median PFS was 4 months (95% CI, 2-6). Fifty-eight percent of patients achieved 12-months OS, with median OS of 17 months (95% CI, 8 to not estimable).

Any-grade adverse events occurred among 53% of patients — the most common of which were diarrhea (10%), fatigue (8%), hypothyroidism (8%) and myalgia (8%) — with 14% of patients experiencing a grade 3 to grade 5 adverse event.

“Although this does not provide cross-comparison as a phase 2 trial, these data show pembrolizumab as monotherapy compares favorably to other treatments; for example, in CheckMate 459 of nivolumab [Opdivo, Bristol Myers Squibb] vs. sorafenib, nivolumab had median OS of 16.4 months, and atezolizumab [Tecentriq, Genentech/Roche] plus bevacizumab [Avastin, Genentech] had median OS of 19 months, and here, OS is 17 months,” Van Laethem told Healio.

Future areas of research include to “identify predictive biomarkers to immunotherapy, [further] evaluate pembrolizumab alone in this subset and combine pembrolizumab with a tyrosine kinase inhibitor antiangiogenic,” he added.


Finn RS, et al. Abstract 267. Presented at: Gastrointestinal Cancers Symposium (virtual meeting); Jan. 15-17, 2021.
Van Laethem J-L, et al. Abstract 297. Presented at: Gastrointestinal Cancers Symposium (virtual meeting); Jan 15-17, 2021.
Yau T, et al. Abstract LBA30_PR. Presented at: European Society for Medical Oncology Congress; Sept. 27-Oct.1, 2019; Barcelona, Spain.


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