The European Commission has approved Opdivo (nivolumab) as a second-line treatment for adults with advanced inoperable, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC), who previously were treated with fluoropyrimidine and platinum chemotherapy agents.
This decision follows a positive recommendation by the Committee for Medicinal Products for Human Use (CHMP), a branch of the European Medicines Agency. With this approval, Opdivo is now the first immunotherapy able to treat ESCC patients in Europe.
“Today’s approval marks a critically important milestone for those living with esophageal squamous cell carcinoma, as this is the first time an immunotherapy treatment option has been approved in the European Union for this patient population,” Ian M. Waxman, MD, development lead of gastrointestinal cancers at Bristol Myers Squibb, the therapy’s developer, said in a press release.
“We are proud of our work in advancing treatment options for people living with upper gastrointestinal cancers, and we look forward to working with European stakeholders to bring Opdivo to more eligible patients who may benefit,” Waxman said.
Opdivo is an immune checkpoint inhibitor that has been approved, both alone and in combination with other therapies, for different types of cancers, including melanoma, lung, kidney, liver, and esophageal cancer.
It works by blocking the activity of the PD-1 protein receptor found on the surface of immune T-cells, which is often hijacked by cancer cells to avoid being detected and eliminated by these immune system cells.
The European Commission’s decision was based on data from the ATTRACTION-3 Phase 3 trial (NCT02569242), which assessed Opdivo’s safety and efficacy as a second-line therapy for patients with advanced inoperable or recurrent ESCC, who failed to respond to standard first-line chemotherapies.
During the trial, sponsored by Ono Pharmaceutical, 419 patients were randomly assigned to either Opdivo at a dose of 240 mg every two weeks, or to one of two chemotherapy agents (docetaxel or paclitaxel) selected by study investigators. Treatment continued until disease progression, unacceptable toxicity, voluntary withdrawal, or the study’s completion.
Its main goal was to determine if Opdivo was superior to chemotherapy at extending survival. Secondary goals included the therapy’s safety, its ability to prolong the time patients lived without disease worsening, as well as the proportion of patients who responded to treatment.
Data from ATTRACTION-3 showed the study met its main goal, with Opdivo significantly prolonging the time patients lived, to a median of 10.9 months compared to 8.4 months for the chemotherapy group — lowering their risk of death by 23%.
Additional findings also showed a higher proportion of Opdivo-treated patients alive after 18 months than was evident among those on chemotherapy (31% vs. 21%).
This survival benefit was seen in all enrolled patients, regardless of the levels of PD-L1 found on their tumors. (PD-L1 is a protein on tumor cells that normally predicts patients’ responses to immune checkpoint inhibitors like Opdivo.)
Although the proportion of patients who responded to treatment in both groups was identical (19% for Opdivo and 22% for chemo), those treated with Opdivo had longer responses (median of 6.9 vs. 3.9 months).
An exploratory analysis of patient-reported outcomes also showed that Opdivo significantly improved participants’ overall quality of life compared with chemo.
Opdivo’s safety profile was found to be favorable, and consistent with that reported in previous studies of patients with solid tumors.
Safety analyses also showed fewer patients on Opdivo experienced treatment side effects compared with those on chemo (66% vs. 95%). Likewise, the incidence of severe or life-threatening side effects was lower among those treated with Opdivo (18% vs. 63%).
The proportion of patients who discontinued treatment due to side effects was similar in both groups (9%).
European countries now join five others, including the U.S. and Japan, that have approved Opdivo to treat people with advanced ESCC who previously received, but failed to respond to, standard chemotherapy.