Harnessing the power of the immune system to fight advanced head and neck cancers topped the list of breakthroughs for several otolaryngologists who were asked to identify recent research that has transformed clinical care.
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February 2020But that excitement is a relatively new development for the profession. Indeed, for many years, otolaryngologists could not be blamed for feeling like they’d been left on the sidelines while immune checkpoint inhibitors and other immunotherapies scored victories against a wide range of malignancies.
“Think about it: For years, cisplatin had been our primary chemotherapy drug for head and neck cancers, even though it was first approved in 1978,” said Jennifer R. Grandis, MD, professor of otolaryngology–head and neck surgery at the University of California, San Francisco. “And while cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, was approved in 2006, after 13 years of clinical use, it’s been a bit of a disappointment in terms of achieving any major gains in survival.”
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That’s why the more recent approvals of pembrolizumab and nivolumab are such a promising development for patients with advanced head and neck squamous cell carcinoma (HNSCC), Dr. Grandis told ENTtoday. “It now gives the multidisciplinary team of medical oncologists, radiation oncologists, and head and neck surgeons two new tools for augmenting the immune system to target the cancer, rather than having to rely on more highly toxic regimens.”
The efficacy of pembrolizumab (Keytruda, Merck Sharp and Dohme Corp.), a programmed death receptor-1 (PD-1) inhibitor, is a case in point, as evidenced in the KEYNOTE-048 trial that led to the drug’s full approval for HNSCC in 2019 (ClinicalTrials.gov Identifier: NCT02358031). The median overall survival (OS) was 13.0 months for the pembrolizumab plus chemotherapy arm and 10.7 months for the cetuximab plus chemotherapy arm (hazard ratio [HR] 0.77; 95% confidence interval [CI]: 0.63, 0.93; P=0.0067), according to a U.S. Food & Drug Administration press release announcing the approval. In a subgroup of patients with high PD-L1 expression, the OS difference was a bit more pronounced: 14.9 months for the pembrolizumab arm versus 10.7 months for the cetuximab plus chemotherapy arm (HR, 0.61; 95% CI, 0.45-0.83; P=0.0015), according to the FDA.
The benefits of nivolumab (Opdivo, Bristol-Myers Squibb) tell a similar story. Approved in 2016 for patients with HNSCC that has progressed or metastasized after platinum-based chemotherapy, the drug has achieved some of its most impressive OS gains in the CheckMate 141 trial (Oral Oncol 2018;81:45-51). The drug “nearly tripled” OS rates at a minimum of 24 months (16.9%) versus standard therapy (6.0%), first author Robert L. Ferris, MD, PhD, the director of the University of Pittsburgh Medical Center Hillman Cancer Center, told ENTtoday.