The European Commission has approved a combination of Opdivo (nivolumab) and Yervoy (ipilimumab) plus two cycles of platinum-based chemotherapy as a first-line treatment for people with advanced non-small cell lung cancer (NSCLC) that contain no mutations in the EGFR or ALK genes.
The approval follows a positive recommendation from the Committee for Medicinal Products for Human Use, a branch of the European Medicines Agency. It marks the third indication for Opdivo plus Yervoy-based combinations in the EU, following previous approvals for advanced melanoma and certain types of kidney cancer.
“The European Commission’s approval of Opdivo plus Yervoy with two cycles of chemotherapy is an important milestone for patients with metastatic non-small cell lung cancer who face a difficult prognosis despite recent advances,” Abderrahim Oukessou, MD, vice president, thoracic cancers development lead at Bristol Myers Squibb, said in a press release.
“We look forward to collaborating with a broad range of European stakeholders to bring this unique combination of two potentially synergistic immunotherapies with chemotherapy to eligible patients with lung cancer,” he added.
Opdivo and Yervoy, both developed by Bristol-Myers Squibb, belong to a class of medications called immune checkpoint inhibitors that work to suppress certain mechanisms used by cancer cells to avoid being targeted and destroyed by the immune system.
These two medications both block proteins found on the surface of immune T-cells — immune cells involved in fighting cancer — boosting distinct immune mechanisms. Yervoy acts on the CTLA-4 protein, helping activate new T-cells, some of which become long-lasting memory-T-cells, while Opdivo blocks another protein called PD-1 and helps existing T-cells locate tumors.
In addition to the European Union, the Opdivo-Yervoy-chemo triple combination has been approved in 11 other countries, including the U.S. and Canada, for the same indication.
These approvals were based on data from the ongoing CheckMate-9LA Phase 3 clinical trial (NCT03215706), which enrolled 719 patients with metastatic or recurrent NSCLC who had not received prior systemic treatment.
Participants were randomly assigned to receive either intravenous (into-the-vein) injections of Opdivo, Yervoy, and two cycles of platinum-based chemotherapy, or up to four cycles of chemotherapy, followed by optional maintenance therapy with pemetrexed.
The main goal was to evaluate whether the triple combo was superior to standard chemotherapy at prolonging survival. Secondary objectives included the time patients lived without disease progression (progression-free survival), the proportion of participants responding to treatment, and survival outcomes of patients with different PD-L1 status.
Of note, PD-L1 status, or the amount of PD-L1 found on a patient’s cancer, is usually seen as a predictor of responses to immunotherapies, like Opdivo, that target the PD-1 or PD-L1 proteins.
Recently, Bristol-Myers presented full data from the trial showing that the immunotherapy combination outperformed standard chemotherapy in several key measures, including overall survival, progression-free survival, and response rates.
After a minimum follow-up of 12.7 months, the triple combo reduced the risk of death by 34%, with participants on the triple combo living significantly longer (15.6 months) than those given standard chemotherapy (10.9 months).
The combination also helped patients live longer without signs of cancer worsening (6.8 months vs. 5.0 months), representing a reduction of 30% in the risk of disease progression or death. Moreover, it significantly increased the proportion of patients responding to treatment — 38% vs. 25%.
Notably, all clinical benefits were consistent across different patient subgroups, with the results independent of PD-L1 levels and histology — whether the cancer originated from squamous or non-squamous cells.
The majority of adverse reactions in the triple combo were mild to moderate in severity, and included fatigue (36%), nausea (26%), rash (25%), diarrhea (20%), itchy skin (18%), lower appetite (16%), hypothyroidism (15%) and vomiting (13%).
Severe to life-threatening adverse events were reported in 47% of patients receiving the triple combo compared to 38% of those on chemotherapy alone.
“Access to innovative medicines is key to improve outcomes for people impacted by lung cancer,” said Anne-Marie Baird, president of Lung Cancer Europe. “We are pleased to see new treatment options approved that may potentially help more people with metastatic non-small cell lung cancer.”
