FDA Approves Keytruda for Head and Neck Cancer

Keytruda is a humanized monoclonal antibody that increases the ability of the immune system to help detect and fight tumor cells.

The FDA on Monday approved a 200-mg fixed dose formulation of pembrolizumab (Keytruda) administered every 3 weeks for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), with disease progression on or after platinum-containing chemotherapy.

Merck’s Keytruda is a humanized monoclonal antibody that increases the ability of the immune system to help detect and fight tumor cells, by blocking the interaction between PD-1 and its ligand PD-L1 and PD-L2. The approval was based on the results from a multi-cohort, non-randomized, open-label phase 1b study called KEYNOTE-012, which examined the safety and efficacy of Keytruda in HNSCC patients.

“Head and neck squamous cell carcinoma presents unique challenges including limited treatment options, especially for patients with recurrent or metastatic disease,” said Holly Boykin, executive director of Head and Neck Cancer Alliance. “We welcome the approval of Keytruda as a new treatment option for people whose lives are impacted by this devastating disease.”

To evaluate the safety of Keytruda, researchers enrolled 192 patients with recurrent or metastatic HNSCC and ECOG performance status of zero or 1. Efficacy was evaluated in 174 of these patients, who had disease progression on or after platinum-containing chemotherapy administered for recurrent or metastatic HNSCC, or following platinum-containing chemotherapy administered as part of induction, concurrent, or adjuvant therapy.

Ninety-five percent of patients enrolled had undergone prior radiation therapy, with the median number of prior lines of therapy for HNSCC being 2. Participants were given 10-mg/hg of Keytruda every 2 weeks (n=53), or a 200-mg fixed dose every 3 weeks (n=121) until unacceptable toxicity or disease progression occurred.

Those who did not experience disease progression were treated for up to 24 months. Patients who experienced subsequent disease progression could have treatment reinitiated with Keytruda administered for up to 1 additional year.

The study was assessed by an independent review facility that used the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 to measure the primary efficacy outcome measurers of objective response rate (ORR) and duration of response (DOR), as assessed by blinded independent central review.

The results of the efficacy analysis showed an ORR of 16% (95% CI: 11, 22), with a complete response rate of 5%. The median follow-up time was 8.9 months, and responses of 6 months or longer were observed in 82% (n=23/28) of responding patients.

Regardless of human papilloma virus status or dosage regimen, the ORR and DOR were found to be similar. In HNSCC patients who received Keytruda, 45% experienced serious adverse reactions, with the most frequent being confusional state, dyspnea, pleural effusion, pneumonia, respiratory failure, and vomiting.

The incidence of adverse reactions was similar between dosage regimens. The most common adverse reactions occurred in at least 20% of patients, and included fatigue, decreased appetite, and dyspnea.

These reactions in HNSCC patients were generally similar to the rates observed in patients with melanoma and non-small cell lung cancer, with the exception of increased incidences of facial edema, and new or worsening hypothyroidism.

“Today’s approval represents a meaningful advance for the oncology community, as well as for our head and neck cancer clinical program,” said Roger M. Perlmutter, president of Merck Research Laboratories. “Together with prior approvals in the treatment of other tumor types, today’s action by the FDA underscores our tireless commitment to addressing the unmet needs of patients suffering from a broad range of cancers.”