The European Commission has approved a combination of Keytruda (pembrolizumab) plus standard chemotherapy for the initial treatment of metastatic squamous non-small cell lung cancer (NSCLC), Merck (known as MSD outside the U.S. and Canada) announced.
The approval — which makes the combination available in all 28 member nations of the European Union, along with Iceland, Lichtenstein, and Norway — is based on findings from the KEYNOTE-407 Phase 3 trial (NCT02775435), where the combination extended patients’ lives by 4.6 months and delayed disease progression or death by a median of 1.6 months.
“In KEYNOTE-407, first-line treatment with Keytruda in combination with chemotherapy resulted in significant improvements in overall survival for patients with metastatic squamous non-small cell lung cancer, regardless of PD-L1 expression,” Luis Paz-Ares, MD, chair of the medical oncology department, Hospital Universitario Doce de Octubre, Madrid, Spain, said in a press release.
“Lung cancer is the leading cause of cancer death in Europe, so this approval marks an important milestone for the patients and families facing this difficult-to-treat type of lung cancer,” he said.
Keytruda is an immune checkpoint inhibitor that binds to the PD-1 receptor on immune cells and prevents the binding of the PD-L1 ligand produced by cancer cells. Cancer cells use this mechanism to evade immune surveillance, and thus, Keytruda is meant to restore a functional immune system that effectively fights cancer.
KEYNOTE-407 recruited 559 squamous NSCLC patients whose disease had spread to distant organs, to determine whether the Keytruda add-on improved the time patients lived without signs of disease worsening and extended their survival.
Participants were randomly assigned Keytruda plus chemotherapy — Paraplatin (carboplatin) and Taxol (paclitaxel) every three weeks, or weekly Abraxane (nab-paclitaxel) — or a placebo plus chemotherapy.
Chemotherapy was given for four three-week cycles, while Keytruda treatment lasted up to 35 cycles.
Researchers found that Keytruda extended the time patients lived without disease worsening from 4.8 months to 6.4 months, representing a 44% reduction in the risk of disease progression or death. Similarly, the treatment lengthened patients’ lives from a median of 11.3 to 15.9 months, with a 36% reduction in the risk of death.
Keytruda also increased the number of patients responding to treatment — 58% versus 38%, as well as the duration of responses — 7.7 months versus 4.8 months.
This benefit was seen across multiple patient subgroups, regardless of PD-L1 status (a biomarker that often predicts responses to Keytruda), site of recruitment, and type of chemotherapy.
The most frequent adverse reactions among Keytruda-treated patients were nausea, anemia, fatigue, constipation, diarrhea, low levels of neutrophils, and low appetite. However, serious side effects were similar in both groups — 67% versus 66%.
In addition to the recently approved indication, Keytruda is also approved in Europe for first-line treatment of NSCLC patients with metastatic non-squamous disease without EGFR or ALK mutations, and for patients with squamous and nonsquamous disease with high PD-L1 levels.
It is also approved for patients with advanced NSCLC whose tumors produce the PD-L1 factor and who have received at least one prior chemotherapy regimen.