A committee of the European Medicines Agency has recommended the approval of Opdivo (nivolumab) for the treatment of people with advanced, inoperable, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) who previously received a chemo regimen containing fluoropyrimidine and a platinum agent.
The European Commission will review this opinion from the Committee for Medicinal Products for Human Use (CHMP) before making a decision. If approved, Opdivo will become the first immunotherapy available in Europe for a cancer in the upper gastrointestinal tract.
“We look forward to the [European Commission]’s final decision, which could mark the first time an immunotherapy is approved for any upper gastrointestinal cancer in the EU,” Ian M. Waxman, MD, development lead of gastrointestinal cancers at Bristol Myers Squibb, said in a press release.
Opdivo, developed by Bristol Myers Squibb, is an immune checkpoint inhibitor that blocks a mechanism used by cancer cells to avoid being targeted and destroyed by immune cells.
Specifically, it targets a protein called PD-1 on the surface of immune cells and prevents it from interacting with its ligands on cancer cells, thereby enabling immune cells to recognize and eliminate cancer cells more effectively.
Both the FDA’s approval and CHMP’s recommendation were based on data from ATTRACTION-3 (NCT02569242), a multicenter Phase 3 clinical trial that is investigating Opdivo’s safety and efficacy in ESCC patients who were resistant or intolerant to first-line combination therapy with fluoropyrimidine and platinum-based therapies.
In the trial, 419 individuals were randomly assigned to Opdivo or standard chemotherapy with docetaxel or paclitaxel, all given by intravenous (into-the-vein) infusions until disease progression or unacceptable toxicity.
ATTRACTION-3 met its primary goal of extending overall survival, with patients on Opdivo living significantly longer (a median of 10.9 months) than those receiving the chemo regimen (8.4 months). Overall, this meant that Opdivo reduced the risk of death by 23%, compared to the chemotherapy.
Additional results continued to demonstrate a survival benefit after 18 months, with more patients in the Opdivo group than on chemo being alive at that time (31% vs. 21%).
Importantly, this survival benefit was observed regardless of PD-L1 status, or the presence of PD-L1 in tumor cells, a measure that normally predicts responses to immune checkpoint inhibitors like Opdivo.
A similar proportion of patients responded to Opdivo and chemo (19.3% vs. 21.5%), but responses to Opdivo lasted substantially longer (6.9 months) compared to chemotherapy (3.9 months).
Although Opdivo did not significantly extend the time patients lived without signs of disease progression, an exploratory analysis showed a significant improvement in patient-reported quality of life in people receiving the medication.
Opdivo also led to fewer treatment-related adverse events than chemo (66% vs. 95%), and to a lower incidence of severe or life-threatening treatment-related adverse events (18% vs. 63%). A similar proportion of patients in the two groups discontinued treatment.
“This positive CHMP opinion underscores the potential of Opdivo in the EU treatment landscape for esophageal squamous cell carcinoma, with the ATTRACTION-3 trial showing clinically meaningful survival coupled with a favorable safety profile,” said Waxman.
“We remain committed to continuing to explore the potential benefits of Opdivo in earlier settings of esophageal cancer,” he added.