FDA Approves Keytruda for Head and Neck Cancer

An accelerated FDA approval has been granted to the immunotherapy Keytruda for patients with recurrent or metastatic head and neck squamous cell carcinoma following progression on a platinum-containing chemotherapy.
BY Silas Inman
PUBLISHED August 06, 2016
An accelerated FDA approval has been granted to the immunotherapy Keytruda (pembrolizumab) for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) following progression on a platinum-containing chemotherapy. Merck, the developer of pembrolizumab, announced the approval.
In supporting evidence for the new indication, which was from the phase 1b KEYNOTE-012 study, Keytruda showed an objective response rate (ORR) of 16 percent, which included a complete response (CR) rate of 5 percent. Responses lasted for ≥6 months for 82 percent of patients. Keytruda was approved regardless of PD-L1 expression at a fixed dose of 200 mg every 3 weeks. 
“Head and neck squamous cell carcinoma presents unique challenges including limited treatment options, especially for patients with recurrent or metastatic disease,” Holly Boykin, executive director, Head and Neck Cancer Alliance, said in a statement. “We welcome the approval of Keytruda as a new treatment option for people whose lives are impacted by this devastating disease.”

In the KEYNOTE-012 trial, 192 total patients with recurrent/metastatic HNSCC received two doses of Keytruda. In the first arm, patients with PD-L1-postive HNSCC received the PD-1 inhibitor at 10-mg/kg (n = 60). In the second group, patients received Keytruda at 200 mg every 3 weeks regardless of PD-L1 status (n = 132).
The approval was based solely on an assessment of 174 patients treated with a prior platinum-based regimen. In this group, 53 patients received the 10 mg/kg dose and 121 got the 200 mg dose of Keytruda.
The median age of patients across the full study was 60 years (range, 20-84), and the majority were males (83 percent). Overall, the median number of prior therapies was 2, with 45 percent having received ≥3 lines of systemic therapy. Fifty-seven percent of patients had received prior platinum therapy and cetuximab. The ECOG performance status was primarily 1 (70 percent) and most patients had metastatic disease (88 percent).
In patients treated with a prior platinum-based agent (n = 174), the ORR was 17 percent, with a CR rate of 5 percent in the data presented at ASCO. The median duration of response had not yet been reached and was similar across both doses of Keytruda.

In data for the full study, 4 percent of patients had experienced a complete response (CR) and 14 percent had a partial response. Sixty percent of patients experienced a decrease in target lesion size, and 65 percent of responders remained on therapy. The median duration of response was not yet reached, with 71 percent of responses lasting 12 months.
Median progression-free survival was 2.0 months with Keytruda (95 percent CI, 1.9-2.1). The 6-month PFS rate was 25 percent and the 12-month rate was 17 percent. Median overall survival (OS) across evaluable patients was 8.0 months for the immunotherapy (95 percent CI, 6-10). The 6-month OS rate was 58 percent. At 12 months, 38 percent of patients remained alive.
Treatment-related adverse events (AEs) were experienced by 64 percent of the 192 patients enrolled. Grade 3/4 AEs occurred in 13 percent of patients. Overall, 6 percent of patients discontinued therapy due to treatment-related AEs.
The most common treatment-related AEs were fatigue (22 percent), hypothyroidism (10 percent), rash (10 percent), pruritus (8 percent), decreased appetite (8 percent), pyrexia (6 percent) and nausea (6 percent). Treatment-related grade 3/4 AEs included liver enzyme increases, fatigue, decreased appetite, low sodium, pneumonitis, facial swelling and hypothyroidism.
“Head and neck cancer is a complex disease that historically has been associated with high recurrence rates and poor long-term outcomes, highlighting the critical need for new treatment options,” Tanguy Seiwert, associate director of the Head and Neck Cancer Program and assistant professor of medicine at The University of Chicago, said in a statement. “The approval of Keytruda for previously treated patients with recurrent or metastatic head and neck squamous cell carcinoma is an important step forward in treating this disease.”
A full approval is contingent upon confirmatory results from a larger study. Currently, the phase 3 KEYNOTE-040 study is comparing Keytruda with methotrexate, docetaxel, or cetuximab in 466 patients with recurrent or metastatic head and neck cancer. The primary completion date for this study is January 2017, and the study has fully accrued. (NCT02252042).
In a second phase 3 study, Keytruda is being explored as a frontline treatment for patients with recurrent or metastatic HNSCC. The immunotherapy is being compared with platinum-based chemotherapy plus 5-FU and cetuximab or in combination with platinum-based therapy and 5-FU. This study plans to enroll 780 patients, with an estimated primary completion date of November 2017 (NCT02358031). 
“Today’s approval represents a meaningful advance for the oncology community, as well as for our head and neck cancer clinical program,” Roger M. Perlmutter, president, Merck Research Laboratories, said in a statement. “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.”

Mehra R, Seiwert TY, Mahipal A, et al. Efficacy and safety of Keytruda in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): Pooled analyses after long-term follow-up in KEYNOTE-012. J Clin Oncol. 2016;34 (suppl; abstr 6012).
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