Immune Checkpoint Inhibitors in Head and Neck Cancers Offer Different Treatment Approaches

A NUMBER OF COMMON cancers were covered at the 2019 Directions in Oncology Pharmacy™ conference. Of great interest to conference attendees was a presentation on head and neck cancer and the evolving paradigm that employs immune checkpoint inhibitors. Presenter Ashley E. Glode, PharmD, BCOP, assistant professor, Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, emphasized the use of these novel agents for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC). Glode’s goal was to identify benefits to the health care team when pharmacists are full clinical partners and especially when patients receive oncology immunotherapies.

The importance of this session was clear when Glode delineated the main types of head and neck cancer, made it clear that squamous cell carcinoma accounts for more than 90% of new cases, and that it is the eighth most common cause of cancer in men. Five-year survival varies by type, stage, and patient factors, but traditionally, this has been a difficult type of cancer to treat.

Researchers continue to look into factors that contribute to this type of cancer, and their emphasis is often prevention. Frequent dental examination and use of sunscreen and lip balm with adequate sun protection factor can prevent these cancers somewhat, and individuals who wear dentures need them to fit well. First and foremost, however, tobacco and alcohol consumption have strong links to head and neck cancers.

Human papillomavirus (HPV) vaccination and limiting the number of sexual partners appears to be an emerging area of research. Of note, individuals who develop head and neck cancer and have a positive HPV status tend to be more responsive to treatment and survive longer than those who do not. Smoking has been associated with decreased overall survival and decreased progression-free survival, and the size of the tumor and nodal status at diagnosis have significant repercussions. Larger tumors are associated with poor prognosis.

Guidelines indicate that there are a number of treatment options for head and neck cancers. These include surgery, radiation, traditional chemotherapies, targeted therapies, immunotherapies, combination treatments, and clinical trials. Surgery may or may not be beneficial, and if the cancer is larger or located in a difficult-to-access area, patients may need more than one surgery. However, sometimes it is impossible to remove tumors surgically. Patients need to work with their physicians if they choose surgery to determine which adverse effects (AEs) are likely, and if they will have any facial disfigurement. These are serious concerns. Radiation is also used frequently, and can have AEs including scarring, dental and oral side effects, and difficulty swallowing.

For decades, the standard of care was chemotherapy with platinum agents and antimetabolites, including fluorouracil. All of these are important in advanced disease. Most are given in combination regimens, and when radiation is employed, cisplatin is the preferred option. Pharmacists are familiar with common AEs including myelosuppression, nausea, vomiting, gastrointestinal involvement, and fatigue.

More recently, targeted therapies have been available for patients. Among the anti-epidermal growth factor receptor (EGFR) agents, afatinib and cetuximab can be used because EGFR overexpression is present in more than 90% of HNSCC. Cetuximab is often employed for first-line therapy for metastatic disease in combination with cisplatin. Two programmed cell death protein 1 (PD-1) inhibitor monoclonal antibodies have proven efficacy in this disease, nivolumab and pembrolizumab. Here too, these biologics address a common problem in HNSCC: Programmed deathligand 1 (PD-L1) overexpression is present in between 50% and 60% of patients and can be detected by laboratory testing. Both nivolumab and pembrolizumab are options for patients with metastatic/unresectable recurrent HNSCC following disease progression while on or after platinum-based therapy. Glode shared exciting data that led to the first-line use of pembrolizumab earlier in 2019. The KEYNOTE-048 trial demonstrated superior outcomes for the use of pembrolizumab with platinum-based chemotherapy and pembrolizumab monotherapy (single agent only if the tumors express PD-L1 (CPS ≥1) as new first-line standard-of-care therapies for recurrent and metastatic HNSCC.

Glode also discussed some of the immunotherapies that are under investigation. Many of them are immune checkpoint inhibitors and are being evaluated as adjuvant therapies, in combination regimens, and as neoadjuvant therapies before surgery. They are also being explored in maintenance settings.

Immune checkpoint inhibitors increase the immune system’s activity so most of their AEs are immune related (irAEs). Often these have a delayed onset and occur weeks to months or even after therapy has ceased. They are typically mild and reversible. However, there is one exception and that is endocrine toxicity. The best way to manage irAEs is supportive care, corticosteroids, and holding the therapy if the AE is significant. Most of these effects will resolve within weeks to months.

Glode emphasized that corticosteroid treatment used to treat irAEs has risks including hyperglycemia, fluid retention, anxiety, and adrenal insufficiency. If used over the long term, they can cause or contribute to Cushingoid features, osteoporosis, glaucoma, muscle weakness, and an increased tendency to develop opportunistic infections.

Glode indicated that it is not clear why some patients have serious reactions to immune checkpoint inhibitors, and it is also unclear if these reactions correlate with improved antitumor response. Managing these AEs with immunosuppression does not result in poor treatment outcomes. In most cases, patients interrupt their checkpoint inhibitor therapy briefly, but dose reductions are not used.

A number of oncology specialists are always part of the interprofessional team, including medical, surgical, and radiation oncologists in addition to dietitians, speech language pathologists, dentists, psychiatrists, and social workers. Including a pharmacist on the team can improve care considerably if they employ their patient education skills and become involved in supportive care. They are also exceptional at AE management, pain management, and as providers of tobacco and alcohol cessation coaching. Pharmacists can ensure that patients are appropriately immunized with HPV vaccine, and recommend alternative dosage forms when patients are struggling.