Neoadjuvant Use Shows New Promise for Immunotherapy in Head and Neck Cancer

Keck Medicine of USC head and neck surgeon Uttam K. Sinha, MD, discusses if adding neoadjuvant and adjuvant immunotherapy to standard-of-care treatment for head and neck cancers may improve event-free survival.

Patients with locally advanced, resectable head and neck squamous cell carcinoma (HNSCC) — a common form of head and neck cancer that arises from the lining of the mouth, throat or sinuses — have conventionally been treated with surgery followed by adjuvant radiotherapy. For patients with stage 3 and 4 HNSCC, adjuvant chemotherapy may also be added. Despite treatment, however, approximately one-third of patients eventually see their cancer relapse within a year, with more than half dying within five years.

An emerging field of research is studying whether immunotherapy, when added to the standard of care, could help improve event-free survival for some patients. Keck Medicine of USC head and neck surgeon Uttam K. Sinha, MD, director of the USC Head and Neck Center, part of the USC Caruso Department of Otolaryngology – Head and Neck Surgery and Keck Medicine of USC, discusses whether neoadjuvant administration of immunotherapy drug pembrolizumab before surgery may make a difference.

Immunotherapy is newer in head and neck cancers

“Those who have a high score for PD-L1 expression will be more sensitive to immunotherapy,” Sinha points out.

At the USC Head and Neck Center, he adds, tissue samples from head and neck cancer patients are routinely genomically analyzed to determine the level of PD-L1 expression within, indicating which patients might be better candidates for immunotherapy.

New consideration for immunotherapy in head and neck cancers

Sinha points to a recent phase 3 trial that compared event-free survival between patients who received the standard of care only (surgery and adjuvant radiotherapy, with or without chemotherapy) and patients who received standard of care plus neoadjuvant and adjuvant immunotherapy (pembrolizumab). The pembrolizumab subjects underwent two cycles of neoadjuvant pembrolizumab, then underwent surgery. Post-surgery, they received radiotherapy, with or without chemotherapy, plus 15 cycles of adjuvant pembrolizumab. Subjects, especially those with a high expression of PD-L1, who were treated with neoadjuvant and adjuvant pembrolizumab in addition to the standard of care saw significantly improved event-free survival compared to the control group.

Sinha explains that pembrolizumab may be more effective when given before surgery because the immune system — particularly T-cells — is more intact. Lymph nodes, which are typically removed during surgery, are rich in immune cells that play a critical role in immune-mediated tumor clearance. By administering pembrolizumab before lymph node removal, the treatment can more effectively facilitate T-cell priming and a robust immune response to kill cancer cells.

In short, Sinha says, “This drug was more effective when patients have intact lymph nodes.”

He does point out, however, that one current drawback to this treatment course is that it is extensive both in terms of time and cost. “It is a very expensive treatment, and it’s a long-term treatment over the course of at least one or two years,” he says. Getting insurance companies to approve this treatment could be challenging.

Genomic analysis to show that a patient has a high PD-L1 expression and may therefore benefit from the treatment is key, he adds. “We have to make sure that there’s a high expression of this ligand; otherwise, there is no point in spending so much money if the treatment is not going to work,” he says.

Currently, he says, first-line treatment for HNSCC is still surgery and radiotherapy and then chemotherapy as needed. Then, if a tumor reoccurs, immunotherapy could be the next step.

“Neoadjuvant immunotherapy may have the potential to improve overall survival for head and neck cancer patients,” he concludes. “But only more research and time will tell.”

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