Keytruda Improves Survival of Patients with Recurrent or Metastatic Head, Neck Cancer, Phase 3 Trial Shows

First-line treatment with Keytruda (pembrolizumab) in combination with chemotherapy prolongs the survival of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), compared to standard of care treatment, a final analysis of a Phase 3 trial shows.

The findings were presented during an oral presentation, titled “Protocol-specified final analysis of the phase 3 KEYNOTE-048 trial of pembrolizumab (pembro) as first-line therapy for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC),” at the 2019 American Society of Clinical Oncology Annual Meeting, held in Chicago from May 31–June 4.

Keytruda is a checkpoint blockade immunotherapy developed by Merck (known as MSD outside the U.S. and Canada) that has been approved by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency for the treatment of several types of cancer.

It is a monoclonal antibody that has been designed to target and block the activity of the PD-1 receptor, a protein found on the surface of immune cells, preventing cancer cells from avoiding being targeted and killed by immune cells.

Keytruda is currently being tested as a first-line therapy for the treatment of patients with recurrent or metastatic HNSCC in a pivotal, randomized, open-label, Phase 3 trial (NCT02358031), called KEYNOTE-048.

The main goal of the study was to assess whether Keytruda, administered alone or in combination with standard platinum-based chemotherapy — cisplatin or carboplatin plus 5-fluorouracil — led to better clinical outcomes, compared with standard of care treatment, which is a combination of platinum-based chemotherapy agents plus 5-fluorouracil and Erbitux (cetuximab), known as the EXTREME regimen.

After reporting promising findings from an interim analysis of KEYNOTE-048 at the European Society for Medical Oncology 2018 Congress, in Germany, Merck has now announced results from the final analysis of the trial.

According to the new findings, when administered in combination with standard chemotherapy, Keytruda reduced the risk of death by 40% among patients whose tumors and surrounding cells expressed high levels of PD-L1 (the ligand of the PD-1 receptor), corresponding to a combined positive score (CPS) greater than 20.

This was reflected by a significant increase in their overall survival, compared with those treated with the EXTREME regimen (14.7 months versus 11.0 months).

However, no statistically significant differences were found in progression-free survival (PFS, the time patients lived without their disease worsening) between both groups.

Among those whose tumors and surrounding cells expressed any level of PD-L1 (CPS equal or higher than one), Keytruda in combination with standard chemotherapy lowered patients’ risk of death by 35%.

Again, this corresponded to a significant increase in overall survival compared to that of individuals treated with the EXTREME regimen (13.6 months versus 10.4 months).

Patients treated with Keytruda alone had a non-inferior overall survival compared with those treated with the EXTREME regimen (11.5 months versus 10.7 months), which was in agreement with previous findings from the trial’s interim analysis. No significant differences were found on PFS between patients receiving Keytruda alone and those receiving standard of care treatment.

“It is exciting to see the full results from this trial, which is the first study to show superior overall survival over the current standard of care known as the EXTREME regimen,” Danny Rischin, MD, director of the department of medical oncology at the Peter MacCallum Cancer Centre, in Melbourne, Australia, said in a press release.

“Patients with recurrent or metastatic head and neck cancer have a poor prognosis with limited treatment options. These findings underscore the potential of Keytruda monotherapy and in combination with platinum-based chemotherapy to become important new treatment options,” he said.

Added Jonathan Cheng, MD, vice president of clinical research at Merck Research Laboratories: “The full data from KEYNOTE-048 illustrate the impact of Keytruda as monotherapy and in combination with chemotherapy as potential new first-line treatment options for patients with recurrent or metastatic head and neck squamous cell carcinoma.”

Partly based on data from KEYNOTE-048, the FDA has granted Priority Review to the supplemental Biologics License Application submitted by Merck seeking the approval of Keytruda, alone or in combination with standard chemotherapy, as a first-line treatment for patients with advanced HNSCC.

The federal agency has signed a Prescription Drug User Fee Act with a target date of June 10, 2019, and must announce its final decision by then.