Keytruda as First-Line Treatment Improves Head and Neck Cancer Survival
New data show a survival benefit with pembrolizumab (Keytruda) as both a monotherapy and combination treatment with chemotherapy.
Pembrolizumab (Keytruda), Merck’s anti-PD-1 therapy, significantly improved overall survival in patients with head and neck squamous cell carcinoma (HNSCC) as a first-line treatment, according to new clinical trial data.
Pembrolizumab is currently approved for the treatment of second-line recurrent or metastatic HNSCC and is administered at a fixed dose of 200 mg every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Based on interim data from KEYNOTE-48, pembrolizumab showed clinical benefit as a first-line treatment, both as a monotherapy and in combination with chemotherapy. The trial evaluated pembrolizumab monotherapy and pembrolizumab combination therapy compared with the EXTREME regimen (cetuximab with cisplatin or carboplatin plus 5-flourouracil) as a first-line treatment in 882 patients with recurrent or metastatic HSNCC.
The study met its primary endpoint of improved overall survival (OS) for both pembrolizumab monotherapy and pembrolizumab in combination with chemotherapy.
- Pembrolizumab monotherapy improved OS by 39% (HR 0.61 [95% Cl, 0.45-0.83]; p=0.0007) in patients whose tumors expressed PD-L1 with Combined Positive Score (CPS) ≥20 and by 22% (HR 0.78 [95% Cl, 0.64-0.96); p=0.0086) in patients with CPS ≥1, compared with the EXTREME regimen.
- Pembrolizumab in combination with chemotherapy demonstrated improved OS compared with the EXTREME regimen by 23% (HR 0.77 [95% Cl, 0.63-0.93]; p=0.0034), regardless of PD-L1.
Based on the interim analysis, pembrolizumab monotherapy demonstrated non-inferiority in the total population and statistical significance was not achieved for the pembrolizumab combination in patients whose tumors expressed PD-L1 at CPS≥20 and CPS≥1.
“In this study, Keytruda showed the potential to significantly prolong survival when used as first-line therapy for patients whose head and neck cancer had recurred or spread,” lead investigator Barbara Burtness, MD, professor of medicine at Yale School of Medicine and co-director of the Development Therapeutics Research Program at Yale Cancer Center, said in a press release. “This is a devastating cancer when it recurs, and there has not been any advance in first-line treatment for over a decade. It is thrilling to see these new data, which have the potential to alter the standard of care in the first-line treatment of head and neck cancer.”
Merck plans to file a supplemental Biologics License Application with the FDA for a first-line indication based on KEYNOTE-048 data and will include data from the phase 3 KEYNOTE-040 trial as supportive data.
Merck’s KEYTRUDA (pembrolizumab) significantly improved overall survival compared to standard of care, as monotherapy and in combination with chemotherapy, as first-line treatment for patients with recurrent or metastatic head and neck cancer [news release]. Merck’s website. https://www.mrknewsroom.com/news-release/oncology-newsroom/mercks-keytruda-pembrolizumab-significantly-improved-overall-survival. Accessed October 23, 2018.