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Yale Cancer Center Study Shows Checkpoint Inhibitor Prolongs Survival in Patients With Certain Head and Neck Cancers

October 31, 2019

The checkpoint inhibitor pembrolizumab (Keytruda) offers patients with advanced head and neck cancers longer survival time, according to a new global study led by Yale Cancer Center (YCC). The data was published today in the journal The Lancet.

The findings show overall survival was significantly improved through a phase 3 study for participants with previously untreated recurrent or metastatic head and neck cancers, compared to the standard therapy.

“This research demonstrates that use of this checkpoint inhibitor, with or without chemotherapy, should be the first drug used for these types of cancers,” said the study’s lead investigator, Barbara Burtness, M.D., a professor of medicine (Medical Oncology) and co-leader of Developmental Therapeutics at YCC. “This is a very positive advance in treatment for our patients.”

Burtness added early results from this clinical trial, KEYNOTE-048, led to FDA approval earlier this year of pembrolizumab as first-line therapy in untreated, recurrent or metastatic head and neck cancers. Cancers specifically referred to as head and neck squamous-cell carcinoma (HNSCC) include cancers of the oral cavity, oropharynx, hypopharynx, and larynx.

While median survival benefit was calculated in months, some patients treated with pembrolizumab lived much longer and did significantly better than patients who were not treated with the checkpoint inhibitor, Burtness noted.

Overall survival was calculated in 882 participants enrolled in 200 medical centers in 37 countries, who were randomized to one of three different groups: pembrolizumab (301 patients), pembrolizumab and chemotherapy (281), or standard therapy with cetuximab and chemotherapy (300). Cetuximab is a drug designed to shut down a protein which makes cancer cells more responsive to growth factors. The chemotherapy used was platinum and 5-fluorouracil.

Pembrolizumab used alone improved median survival to 14.9 months, compared to 10.7 months for standard therapy. Use of pembrolizumab combined with chemotherapy improved survival to a median of 13 months.

Furthermore, survival differences between patients treated with pembrolizumab and those who weren’t remained very apparent years after treatment. 

Investigators found that at three years, 33% of patients treated with pembrolizumab monotherapy were alive, as well as about 26% of participants in the pembrolizumab/chemotherapy groups, compared with only 8% in the standard treatment arm.

“The difference with immunotherapy is the durability of the effect it has on survival,” Burtness said. “These agents seem to change the tumor microenvironment, altering the natural history of the cancer.”

Toxicity was reduced in patients treated with pembrolizumab monotherapy, and participants in the other two groups experienced about the same level of adverse effects.

This study was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J.

Co-authors of the study include Kevin J. Harrington, Ph.D., The Institute of Cancer Research/The Royal Marsden NHS Foundation Trust National Institute of Health Research Biomedical Research Centre, London; Richard Greil, M.D., Paracelsus Medical University, Salzburg Cancer Research Institute, and Cancer Cluster Salzburg, Salzburg, Austria; Denis Soulières, M.D., Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada; Makoto Tahara, M.D., National Cancer Center Hospital East, Kashiwa, Japan; Gilberto de Castro, Jr., M.D., Instituto do Cancer do Estado de Sao Paulo, Sao Paulo, Brazil; Amanda Psyrri, M.D., National Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece; Neus Basté, M.D., Vall d’Hebron University Hospital, Barcelona, Spain; Prakash Neupane, M.D., University of Kansas Medical Center, Kansas City, KS;  Åse Bratland, Ph.D., Oslo University Hospital, Oslo, Norway; Thorsten Fuereder, M.D., Medical University of Vienna, Vienna, Austria; Brett G.M. Hughes, MBBS, Royal Brisbane and Women’s Hospital and University of Queensland, Brisbane, QLD, Australia; Ricard Mesía, Ph.D., Catalan Institute of Oncology, Hospitalet de Llobregat, Barcelona, Spain; Nuttapong Ngamphaiboon, M.D., Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Tamara Rordorf, M.D., University Hospital, Zurich, Switzerland; Wan Zamaniah Wan Ishak, M.D., University Malaya, Kuala Lumpur, Malaysia; Ruey-Long Hong, M.D., National Taiwan University Hospital, Taipei, Taiwan; René González Mendoza, M.D., Unidad de Investigación en Salud, Chihuahua, Mexico; Ananya Roy, Ph.D., Yayan Zhang, Ph.D., Burak Gumuscu, M.D., Jonathan D. Cheng, M.D., and Fan Jin, M.D., Merck & Co., Inc., Kenilworth, NJ; and Danny Rischin, M.D., Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC, Australia. 

Submitted by Anne Doerr on October 31, 2019