Applying Research Data to Clinical Practice in Managing Head and Neck Cancer

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The 2021 Winship Cancer Institute of Emory University Symposium: Updates in the Management of Head and Neck Cancer explored current paradigms for the multidisciplinary treatment of head and neck cancer.1 Moderated by Nabil F.

Nabil F. Saba, MD, FACP

Nabil F. Saba, MD, FACP

Saba, MD, FACP, the Lynne and Howard Halpern Chair in Head and Neck Cancer Research, Professor and Vice Chair of Hematology and Medical Oncology, and Co-Director of the Head and Neck Cancer Multidisciplinary Program at Winship Cancer Institute, the live symposium featured a host of expert faculty who reviewed new findings and discussed the optimal application of the data in clinical practice.

In an interview with The ASCO Post, Dr. Saba summarized the highlights of the meeting, zeroing in on some of the most important happenings in the management and research of head and neck cancers. 

Meeting Highlights

Currently, a major challenge in the field concerns how best to incorporate immunotherapy in the definitive setting and in early-stage disease. The year 2016 ushered in a new era of immunotherapy in head and neck cancer with the approval of several checkpoint inhibitors. However, discouraging results were seen in studies that added these immunotherapy drugs to the backbone of radiation and cisplatin, Dr. Saba noted.

“I think this year’s meeting was a very good exploration of venues aiming to adequately sequence and add these agents in the definitive setting of head and neck cancer treatment,” he said.

Sessions at the meeting focused on novel immunotherapy combinations in recurrent metastatic disease, with responses potentially being substantial in patients with a high combined positive score. This was highlighted in a review of the CheckMate 651 trial of combined therapy with a PD-1 inhibitor and a CTLA-4 inhibitor.2

Radiation sessions focused on a few pertinent questions: What is the current landscape in the definitive management and re-irradiation management of head and neck cancer? How can immunotherapy be incorporated in that setting?

“Again, more is not necessarily better, and understanding the biology is a more important angle we should focus on, rather than just piling up treatment modalities on top of each other,” Dr. Saba explained. “High-dose radiation or high-dose chemotherapy may actually be counterintuitive within an immune-oncology platform, as low-dose radiation or low-dose chemotherapy may actually be proimmunogenic.”

De-escalation in HPV-Positive Disease

With the recent publication of the ECOG 3311 trial,3 discussions of de-escalation in human papillomavirus (HPV)-positive head and neck cancer have focused on “what’s next,” said Dr. Saba. (For more details on this trial, see page 39.) Is ECOG 3311 setting a new standard of care?

“The trial proves that this approach is valid and useful in low-risk HPV-related disease,” commented Dr. Saba. “However, the question of whether it is equivalent to definitive therapy—in other words, nonsurgical therapy—is a question that deserves to be answered in a subsequent phase III trial.”

Treatment Update

In terms of the management of head and neck cancers, “we’re still collecting the benefits of nivolumab and pembrolizumab in the treatment of recurrent or metastatic disease,” said Dr. Saba. “The widespread use of these agents continues, but should they be used by themselves, or should we use them in combination with chemotherapy?” The answer, he said, depends on patient factors such as disease state and combined positive score.

“Another interesting focus is combining PD-1 inhibitors with tyrosine kinase inhibitors, as we are seeing with efforts to combine pembrolizumab with lenvatinib and other early studies looking at cabozantinib,” he continued. “Given the role of EGFR inhibition in this disease, another obvious focus is combining PD-1 inhibitors with cetuximab.” Data on pembrolizumab and cetuximab appear to demonstrate a very good clinical outcome in terms of disease control and survival, and combination nivolumab and cetuximab appears to be very encouraging in the first-line recurrent or metastatic setting, he noted.

Dr. Saba continued: “I think over the next few years, the first-line single-agent PD-1 inhibitors will be up for grabs in terms of possibly changing the standard of care once more for this group of patients.”

Data on the Horizon

“In terms of current research, I think we are still eagerly awaiting the results of accruing trials,” Dr. Saba said. “Some of them have completed accrual, namely in the definitive setting.”

Trial data will answer some particularly important questions. Why was the JAVELIN trial—comparing avelumab/chemoradiotherapy with standard-of-care chemoradiotherapy—a negative study ( identifier NCT02952586)? KEYNOTE-412 aims to answer the question of whether the addition of pembrolizumab to radiation and chemotherapy in the definitive setting would make a difference in survival (NCT03040999).

“Another trial worth waiting for is the IMvoke010 study [NCT03452137]; this trial uses a maintenance approach, even though enrollment on the trial starts following completion of definitive therapy in a heterogeneous group of patients,” he noted. “It will be interesting to look at results of the role of a maintenance approach, given the results that we’ve seen in lung cancer with the PACIFIC trial.4

In addition, ECOG-ACRIN 3161 (NCT03811015) is particularly important given its focus on HPV-related disease with intermediate clinical risk andis asking the same question regarding the benefit of maintenance nivolumab in these patients. Most events in other studies will be driven predominantly by the HPV-negative group; EA-3161 is still accruing. 

DISCLOSURE: Dr. Saba has served as an advisor and received compensation from Eisai, Astra Zeneca, Merck, WebMD, OncLive, Mirati, Reach MD, Vaccinex, Kura, Biontech, GSK, Aduro, and Pfizer; and has received research funding from BMS and Exelixis.


1. Saba NF: Integrating immunotherapy in the non-surgical definitive management of SCCHN. 2021 Updates in the Management of Head and Neck Cancer. Presented November 6, 2021.

2. Argiris A, et al: Nivolumab + ipilimumab vs EXTREME as first-line treatment for recurrent/metastatic squamous cell carcinoma of the head and neck: Final results of CheckMate 651. ESMO Congress 2021. Abstract LBA36. Presented September 20, 2021.

3. Ferris RL, et al: Phase II randomized trial of transoral surgery and low-dose intensity modulated radiation therapy in resectable p16+ locally advanced oropharynx cancer. J Clin Oncol. October 26, 2021 (early release online).

4. Antonia SJ, et al: Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med 377:1919-1929, 2017.