The first detailed results from the CheckMate -651 trial showed that median overall survival (OS) for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) who received the combination of Bristol Myers Squibb's Opdivo (nivolumab) and Yervoy (ipilimumab) was 13.9 months versus 13.5 months for the EXTREME regimen of cetuximab, cisplatin/carboplatin and fluorouracil. The data were released ahead of presentation at the European Society for Medical Oncology (ESMO) congress.
In July, the company announced that the study failed to meet its primary endpoints, with the combination of the PD-1-blocking antibody Opdivo and the CTLA-4 inhibitor Yervoy failing to significantly improve OS outcomes. The trial randomised 947 platinum-eligible patients with recurrent or metastatic SCCHN to receive treatment in the first-line setting with either Opdivo plus Yervoy or the EXTREME regimen.
Along with the main goal of OS in all randomised patients, the study's other primary endpoint was OS in subjects whose tumours express PD-L1 with a combined positive score (CPS) ≥ 20. At the time the trial was top-lined, Bristol Myers Squibb said that Opdivo plus Yervoy showed a "clear, positive" OS trend for the CPS ≥ 20 subgroup. At ESMO, the results demonstrated that median OS in these patients was 17.6 months for Opdivo plus Yervoy, versus 14.6 months for the EXTREME regimen, although the difference was not significant. The study authors added that "notably, OS in the control arm was better than historical data."
Further results showed that in the CPS ≥ 20 subgroup, two-year OS rates were 41% for Opdivo plus Yervoy, compared to 33% for the EXTREME regimen, while similar benefits in median OS and two-year OS rates were seen in the CPS ≥ 1 subgroup (see table below).
Updated results were also released from the Phase III CheckMate -649 trial, which enrolled adults with previously untreated, unresectable advanced or metastatic gastric cancer, gastroesophageal junction cancer or oesophageal adenocarcinoma, regardless of their PD-L1 expression levels. Data presented at ESMO last year showed that Opdivo plus chemotherapy reduced the risk of death by 29% in the CPS ≥ 5 subgroup, with median OS of 14.4 months, compared with 11.1 months for chemotherapy alone, leading to FDA approval.
The latest results showed that the benefits of Opdivo plus chemotherapy remained with a further one year of follow-up, with a 30% reduction in the risk of death and a 12% improvement in the 24-month OS rate. However, median OS for patients with a CPS ≥ 5 who received the combination of Opdivo and Yervoy was 11.2 months, versus 11.6 months for chemotherapy alone (see table below). Lead investigator Yelena Janjigian noted that the Opdivo plus Yervoy arm of the study was halted early due to "higher toxicity and early death" compared to the other treatment groups.
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