Long-term follow-up data show a continued benefit for patients with advanced hepatocellular carcinoma (HCC) treated with nivolumab and ipilimumab after disease progression on sorafenib, according to investigators from the Checkmate 040 trial.
At a minimum follow-up of 44 months, the 3-year overall survival rate ranged from 30% to 42% in patients who received three different nivolumab-ipilimumab regimens, reported Anthony B. El-Khoueiry, MD, of the University of Southern California in Los Angeles.
“Durable responses were achieved across treatment arms, with the duration of response approaching 4 years in some cases,” Dr. El-Khoueiry said at the 2021 Gastrointestinal Cancers Symposium (Abstract 269).
The Checkmate 040 trial was designed to compare second- or later-line therapy with the two checkpoint inhibitors at two different dose schedules, followed by maintenance therapy, plus a third continuous therapy arm.
The trial included 148 patients with advanced HCC who experienced disease progression on sorafenib or could not tolerate the drug. They were randomly assigned on a 1:1:1 basis to receive:
- Nivolumab at 1 mg/kg plus ipilimumab at 3 mg/kg every 3 weeks for 4 cycles, followed by nivolumab maintenance at 240 mg every 2 weeks (nivo 1 + ipi 3).
- Nivolumab at 3 mg/kg plus ipilimumab at 1 mg/kg every 3 weeks for 4 cycles, followed by nivolumab maintenance (nivo 3 + ipi 1).
- Nivolumab at 3 mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity (nivo 3 + ipi 1 Q6).
Based on earlier results of this trial, the nivo 1 + ipi 3 dose with nivolumab maintenance was approved in the United States for patients with advanced HCC previously treated with sorafenib.
Four years on
“Response outcomes at 44 months of follow-up were consistent with the primary analysis,” Dr. El-Khoueiry said.
The overall response rate at the most recent follow-up was 32% for nivo 1 + ipi 3, and 31% in each of the other arms.
The disease control rate – a combination of complete and partial responses and stable disease – was 54% in the nivo 1 + ipi 3 arm, 43% in the nivo 3 + ipi 1 arm, and 49% in the nivo 3 + ipi 1 Q6 arm.
The 36-month overall survival rates were 42%, 26%, and 30%, respectively. Kaplan-Meier curves for overall survival for both the primary analysis and the long-term follow-up displayed a survival advantage for nivo 1 + ipi 3 compared with the other two arms.
Safety
Treatment-related adverse events occurred more frequently in the nivo 1 + ipi 3 arm, which investigators attribute to the higher dose of ipilimumab. The most common grade 3 or 4 events in this arm were elevated liver enzymes and hyponatremia.
Immune-related adverse events also occurred more frequently in the nivo 1 + ipi 3 arm.
“Most immune-mediated adverse events were reversible and resolved when treated using an established algorithm, with steroids being the most common immune-modulating medication used. There were no additional discontinuations due to immune-mediated adverse events during the longer follow-up,” Dr. El-Khoueiry said.