The following article features coverage from the ASCO Gastrointestinal Cancers Symposium 2021 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

An objective response (OR) to pembrolizumab achieved by landmark time was associated with prolonged overall survival (OS) thereafter in patients with previously treated hepatocellular carcinoma (HCC), according to a post hoc analysis of the KEYNOTE-240 study presented at Gastrointestinal Cancers Symposium.

The KEYNOTE-240 trial ( identifier: NCT02702401) compared pembrolizumab plus best supportive care (BSC) to BSC alone in 413 patients with advanced HCC who received prior sorafenib. Although KEYNOTE-240 investigators observed a clinical benefit with the addition of pembrolizumab, the prespecified criteria for OS or progression-free survival (PFS) were not met.

In the KEYNOTE-240 trial, findings from a landmark analysis showed that OR was prognostic of longer OS in those who received the ICI. The purpose of this post hoc analysis was to determine whether OR at landmark is prognostic of prolonged survival after landmark.

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In the post hoc analysis, the landmark evaluation of OS was conducted at 6, 12, and 18 weeks after randomization for the pembrolizumab group (n=270), and stratified by OR. Responders at each landmark time point were defined as those who achieved a partial or complete response before the landmark. All other patients with a response assessment of stable or progressive disease or who were not evaluable were deemed nonresponders.

At baseline, the median patient age was 70 years and 66 years among responders (n=51) and nonresponders (n=219), respectively. Nearly all patients were classified as Child Pugh class A. BCLC stage varied by responders and nonresponders. Stage B disease was present in 11.8% of responders and 22.8% nonresponders. Stage C disease was present in 88.2% and 77.2% of responders and nonresponders, respectively.

At a median follow-up of 21.2 months, the OR rate was 18.3%. At each landmark analysis, OR was found to be significantly associated with prolonged OS.

At 6 weeks, median OS was not reached in the responder group compared with 12.1 months in the nonresponder group (HR, 0.37; 95% CI, 0.18-0.75). At 12 weeks, the median OS was 20.4 months and 10.8 months in the responder and nonresponder subpopulations, respectively (HR, 0.39; 95% CI, 0.23-0.66). At Week 18, median OS was not reached among responders compared with 10.8 months among nonresponders (HR, 0.37; 95% CI, 0.21-0.63).

The authors concluded that “these results support the association between OR to pembrolizumab and OS observed in KEYNOTE-224.” They noted that additional prospective studies with larger sample sizes are needed to further validate this relationship.

Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study. This clinical trial was supported by Merck Sharp & Dohme Corp.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO GI 2021 meeting by visiting the conference page.


Edeline J, Cattan S, Merle P, et al. Landmark analysis of overall survival (OS) by objective response (OR) in previously treated patients (pts) with advanced hepatocellular carcinoma (aHCC): post-hoc analysis of the randomized, phase III KEYNOTE-240 study. Poster presented at: Gastrointestinal Cancers Symposium; January 15-17, 2021. Abstract 318.