The Committee for Medicinal Products for Human Use (CHMP), a branch of the European Medicines Agency (EMA), has recommended that two regimens of Keytruda (pembrolizumab) be approved in Europe for first-line treatment of metastatic or inoperable recurrent head and neck squamous cell carcinoma (HNSCC).
The CHMP recommends that Keytruda, either alone or in combination with 5-fluorouracil (5-FU) and platinum chemotherapy, be approved as a first-line treatment for those whose tumors contain the programmed death-ligand 1 (PD-L1), a protein that plays a key role in allowing cancer cells to evade the body’s immune system.
CHMP’s recommendation is now being reviewed by the European Commission, which is expected to announce a final decision regarding the approval of both Keytruda regimens before the end of the year.
Keytruda is an immune checkpoint inhibitor developed by Merck (known as MSD outside the United States and Canada) that has been approved by the U.S. Food and Drug Administration (FDA) and by the EMA for the treatment of several types of cancer.
It is a monoclonal antibody that targets and blocks the binding of the PD-1 receptor, a protein found on the surface of immune cells, to the PD-L1 protein found on tumor cells. Cancer cells use this interaction to avoid being targeted and killed by immune cells.
The positive opinion was based on findings from the KEYNOTE-048 Phase 3 trial (NCT02358031), which tested Keytruda either alone or in combination with chemotherapy — cisplatin or carboplatin plus 5-fluorouracil — in patients with recurrent or metastatic HNSCC compared to standard chemo.
Standard-of-care chemotherapy consists of a combination of platinum-based chemotherapy agents plus 5-fluorouracil and Erbitux (cetuximab), known as the EXTREME regimen.
Findings from KEYNOTE-048 showed that when administered in combination with chemotherapy, Keytruda prolonged the survival of patients whose tumors contained high levels of PD-L1 from 11.0 to 14.7 months, reducing the risk of death by 40%.
In addition, those who received Keytruda alone had a non-inferior overall survival compared to those receiving standard-of-care treatment (11.5 months versus 10.7 months), which was in agreement with previous findings from the trial’s interim analysis.
“Head and neck cancer remains a devastating disease with poor long-term outcomes and advances in survival have been difficult to achieve for more than 10 years,” Jonathan Cheng, vice president of clinical research at Merck Research Laboratories, said in a press release.
“The positive EU CHMP opinion further validates the potential of Keytruda, as monotherapy and in combination with chemotherapy, to help patients and address the high unmet need in this aggressive form of head and neck cancer,” Cheng said.
In addition to KEYNOTE-048, Merck is testing the effectiveness of Keytruda as a monotherapy and in combination with other anti-cancer drugs for the treatment of patients with HNSCC in two other Phase 3 trials — KEYNOTE-412 (NCT03040999) and KEYNOTE-689 (NCT03765918). The latter is still recruiting; more information can be found here.
