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. —Jennifer R. Grandis, MD
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February 2020
The drug also demonstrated an OS benefit across the spectrum of PD-L1 expression: ≥1% (HR [95% CI] = 0.55 [0.39-0.78]) and < 1% (HR [95% CI] = 0.73 [0.49-1.09]). Moreover, the OS benefit was seen regardless of tumor human papillomavirus (HPV) status. “In the earlier PD-L1 studies, the initial response rate for HPV-positive cancers was faster and more frequent, but when you look at the long-term data from the CheckMate 141 trial, the HPV-positive and HPV-negative patients had essentially identical survival rates,” Dr. Ferris said.
According to Dr. Ferris, one question has been at the core of studies evaluating immune checkpoint inhibitors for advanced HNSCC: Are they ready to assume first-line status for recurrent or meta static disease, or at the least be used in conjunction with standard-of-care chemotherapy? “As I noted in my recent Lancet article [2019;394:1882-1884], the answer, in short, is yes to both questions,” he said.
Education Is Key
Otolaryngologists can help ensure these new immunotherapy drugs have the maximum chances for success “by becoming immune-literate,” Dr. Grandis said. “Head and neck surgeons need to understand these immune pathways and what these drugs are doing, what they are not doing, and cement partnerships with our medical and radiologist oncologists to pull in the same direction.”
Dr. Ferris agreed. “HNSCC is a unique cancer because about half of cancers are carcinogen-exposed tumors [smoking, alcohol] and half are virus-induced tumors [HPV and Epstein-Barr virus], making HNSCC a unique model to understand why immunotherapy works for some, but not most, patients,” he added.
In addition, “ENT surgeons see the patient first, and obtain the pre- and post-treatment biopsy specimens,” he said. “So ENTs are in unique position to help our colleagues in medical oncology understand how these PD-1 inhibitors are working or not working in real time. By analyzing pre- and post-treatment biopsies, we can better understand responders and non-responders, biomarkers, and resistance pathways in head and neck cancers—potentially applicable to other malignancies.”
Dr. Ferris pointed to another reason why otolaryngologists would benefit from brushing up on their understanding of key immunotherapy concepts: They may find themselves taking on an even more active role in the care of these patients. “Within our lifetimes, I would suggest that we may also be giving the PD-1 inhibitors, because there are oral and subcutaneous versions coming on the market that look promising,” he explained. “It may be that the head-neck surgeons give the antibodies themselves in their office, which makes sense, since the ENT actually sees the patient first. So ENTs need to be aware of these developments—this is not just restricted to medical oncologists.”