The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended the combination of nivolumab and ipilimumab as a frontline treatment for adult patients with unresectable malignant pleural mesothelioma.
The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) as a frontline treatment for adult patients with unresectable malignant pleural mesothelioma (MPM).1
The positive opinion is based on data from the phase 3 CheckMate-743 trial, in which nivolumab plus ipilimumab led to a 26% reduction in the risk of death compared with pemetrexed plus cisplatin or carboplatin in this patient population (HR, 0.74; 95% CI, 0.60-0.91; P = .002).2 The median overall survival (OS) was 18.1 months with the combination (95% CI, 16.8- 21.4) vs 14.1 months with chemotherapy (95% CI, 12.4 -16.2) at 29.7 months of follow-up, and the 2-year OS rates were 41% and 27%, respectively.
“For more than 15 years, no new treatment options that can improve survival have been approved for malignant pleural mesothelioma, and today most patients only live for just over a year from the time of their diagnosis,” said Abderrahim Oukessou, MD, vice president, thoracic cancers development lead, Bristol Myers Squibb, the developer of both agents. “Now, with the positive CHMP opinion for Opdivo plus Yervoy, we are one step closer to helping address the pressing unmet need for effective, proven therapies for this aggressive cancer. We look forward to potentially bringing the first immunotherapy combination that may offer a chance for a longer life to patients in the [European Union].”
In the open-label, CheckMate-743 study, 605 patients with unresectable pleural mesothelioma were randomized 1:1 to receive either nivolumab at 3 mg/kg once every 2 weeks in combination with ipilimumab at 1 mg/kg once every 6 weeks for up to 2 years or chemotherapy with cisplatin or carboplatin plus pemetrexed every 3 weeks. Treatment was given until either disease progression, intolerable toxicities, or up to 2 years for those on the immunotherapy arm.
To be eligible for enrollment, patients could not have received prior systemic therapy and an ECOG performance status of 0 or 1 was required. Patients were stratified based on histology, either epithelial or non-epithelial disease, as well as gender.
The primary end point was OS; secondary end points included objective response rate (ORR), disease control rate, and progression-free survival (PFS) as assessed by blinded independent central review (BICR), and PD-L1 expression as a predictive biomarker.
Further findings showed that the median PFS was shorter in the nivolumab/ipilimumab arm at 6.8 months vs 7.2 months with chemotherapy (HR, 1.00; 95% CI, 0.82-1.21). However, the 1- and 2-year PFS rates were higher with immunotherapy at 30% and 24% vs 16% and 7% with chemotherapy, respectively.
The ORR via BICR was 40% with nivolumab/ipilimumab, which included a 38% partial response (PR) rate and a 2% complete response rate. The ORR was 43% with chemotherapy, which consisted of all PRs. The disease control rate was 77% with the combination compared 85% with chemotherapy.
The median duration of response (DOR) was 11.0 months with nivolumab/ipilimumab compared with 6.7 months with chemotherapy. The median time to response was 2.7 months and 2.5 months, respectively.
Additional findings, which were presented during the 2020 International Association for the Study of Lung Cancer’s World Conference on Lung Cancer Virtual Presidential Symposium in August, demonstrated that the 1-year OS rates in the experimental and control arms were 68% and 58%, respectively. At 2-years, these rates were 41% and 27%, respectively.3
The survival benefit with nivolumab plus ipilimumab was reported across prespecified subgroups, including those with epithelioid or non-epithelioid disease, and those with PD-L1 expression of less than 1% or 1% or higher.
Regarding safety, grade 3/4 treatment-related adverse effects (TRAEs) occurred in 30% of those on nivolumab/ipilimumab vs 32% of those on chemotherapy. Serious TRAEs occurred in 21% and 8% of patients, respectively.
The most common TRAEs with nivolumab and ipilimumab included diarrhea and pruritus. Nausea, anemia, neutropenia, fatigue, decreased appetite, and asthenia were most commonly reported with chemotherapy.